A study of 5-substituted uracils

Supplementary Information for A study of 5-substituted uracils 1. Results from the CSD study. A search of the Cambridge Structural Database (CSD) was performed to find all of the crystal structures that involved 5-substituted uracils, including polymorphs, solvates and co-crystals. The resulting 109 hits (Table S1.1) were first reduced to just those with full structural coordinates available (92) and then the 36 structures which included metallic elements were removed. Additionally, where multiple versions of the same structure were available, just the best one was kept, i.e., the one with hydrogen atoms present, the one where data was collected at a lower temperature and/or the one with the lowest R factor. The remaining 49 structures (Table S1.2) were analysed visually using Mercury with hydrogen bonds being considered present only if the N-H O hydrogen bond angle was 125 but with the default setting for intermolecular interaction distances. Table S1.1 Results from the search of the CSD for all compounds containing the 5-substituted uracil motif, including polymorphs, solvates and co-crystals Refcode R 1 S. G. T (K) a(å) b(å) c(å) α( ) β( ) γ( ) Volume Dcalc Compound Name Fit Criteria ACUFIO 5.61 P2 1/n 150 3.555 18.134 10.635 90 91.39 90 685.398 1.9 catena-((μ3-uracil-5-carboxylato-o,o,o,o')-( ACUFOU 4.24 Cc 120 6.816 15.4 12.088 90 101.701 90 1242.467 1.873 μ2-aqua)-sodium) Metal catena-((μ3-uracil-5-carboxylato- O,O',O'',O''')-(μ3-uracil-5-carboxylic acid- O,O',O'')-potassium) Metal catena-((μ6-hydrogen bis(uracil-5- carboxylato))-rubidium dihydrate) Metal ACUFUA 3.19 P-1 150 4.884 8.412 10.024 112.263 101.56 93.345 369.28 1.946 catena-((μ5-uracil-5-carboxylato- ACUGAH 2.14 P2 1/c 120 7.8301 4.9937 18.9664 90 98.649 90 733.175 2.343 O,O,O,O',O',O',O'')-(μ3-aqua)-rubidium) Metal catena-((μ6-hydrogen bis(uracil-5- ACUGEL 2.35 P-1 150 5.062 8.085 9.1 81.43 83.75 87.99 366.015 2.178 carboxylato))-diaqua-cesium) Metal ADOSBU 8.3 P2 1 295 7.05 16.86 7.347 90 102.98 90 850.973 1.788 Adenosine-5-bromouracil APSURD 4.1 P2 1 295 14.032 6.3076 6.455 90 92.96 90 570.558 1.526 alpha-pseudouridine monohydrate 2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5- AYEBIP 4.5 P21/c 298 7.876 20.352 8.664 90 101.87 90 1359.077 1.702 carboxylic acidmonohydrate 1-(2,4-Dioxo-1,2,3,4-tetrahydropyrimidin-5- yl)-1,2,3,4-tetradeoxy-1,4-imino-beta-dpentitol hydrochloridemonohydrate BEBWIO 6.72 C2/c 295 13.741 7.2 24.483 90 109.322 90 2285.796 1.544 BIKHIN 0 P-1 150 5.4014 23.6232 6.7101 89.931 90.164 90.139 856.191 1.785 5-Fluorouracil 2,2,2-trifluoroethanol No Co-ordinates BIKHIN01 2.8 P2 1 150 5.3976 6.7062 12.1098 90 102.807 90 427.438 1.788 5-Fluorouracil 2,2,2-trifluoroethanol solvate BOMMOF 5.8 P-1 295 9.994 10.298 13.435 100.8 103.46 102.4 1271.688 1.271 5-Uracilylmethyl-triphenylphosphonium chloride ethanolsolvate monohydrate 1

BRURAC01 0 P* 295 7.23 6.85 5.63 90 96 90 277.301 2.287 5-Bromouracil No Co-ordinates BRURAC10 2.7 P21/c 295 8.598 6.886 11.417 90 123.93 90 560.852 2.262 5-Bromouracil CLURAC10 5.8 P21/c 295 8.45 6.842 11.072 90 123.53 90 533.607 1.824 5-Chlorouracil CYSTYM 4.3 P212121 295 9.499 24.072 5.012 90 90 90 1146.044 1.633 alpha-s-cysteinylthymine hydrochloride CYSURC10 10.1 P21 295 14.59 6.82 5.05 90 95.1 90 500.505 1.654 5-S-Cysteinyluracil monohydrate CYTFUR 16.2 P-1 295 4.29 9.59 15.14 111.8 98 101.3 551.542 1.561 CYTFUR01 4.67 P-1 298 4.2629 9.5372 13.9639 102.562 91.055 101.331 542.217 1.588 DAVGAI 5.42 P-1 295 4.98 8.164 9.583 74.25 85.12 88.89 373.623 1.807 Cytosine-5-fluorouracil complex monohydrate Higher R No H 4-amino-2-oxopyrimidine 2,4-dioxo-5- fluoropyrimidinemonohydrate Diaqua-bis(iso-orotato)-magnesium(ii) dihydrate Metal (η5-cyclopentadienyl)-(1-methoxy-2-(5- uracil)ethylidene)-bis(triphenylphosphine)- rutheniumhexafluorophosphate toluene solvate Metal EZUNES 3.94 P-1 173 11.6179 14.376 16.327 94.691 91.172 112.93 2498.96 1.457 FORHAV 3.6 P21/c 295 12.005 9.804 12.628 90 106.02 90 1428.559 1.377 5-(Diphenylphosphino)uracil Higher R Higher T No H FURACL 9.2 P-1 295 9.22 12.66 12.67 89.7 43.9 98.6 1000.085 1.728 5-Fluorouracil FURACL01 4.91 P-1 150 8.6329 9.156 12.5796 99.119 100.021 90.017 966.385 1.788 5-Fluorouracil FURACL02 7.52 P2 1/c 293 5.154 15.001 6.654 90 110.336 90 482.389 1.791 5-Fluorouracil Higher R Higher T FURACL03 5.44 P2 1/c 150 5.0433 14.935 6.6049 90 108.884 90 470.715 1.836 5-Fluorouracil FURACL04 0 P-1 298 8.7588 9.1909 12.6438 81.452 80.697 89.305 993.223 1.74 5-Fluorouracil No Co-ordinates FURACL05 0 P-1 150 8.615 9.183 12.584 98.783 99.89 90.427 968.665 1.784 5-Fluorouracil No Co-ordinates FURACL06 0 P-1 298 8.727 9.209 12.631 80.946 78.9 89.597 983.43 1.757 5-Fluorouracil No Co-ordinates FURACL07 0 P-1 150 8.6394 9.166 12.5994 99.134 99.851 89.965 970.194 1.781 5-Fluorouracil No Co-ordinates FURACL08 0 P-1 150 8.6404 9.1669 12.6104 80.909 79.929 89.97 970.695 1.78 5-Fluorouracil No Co-ordinates FURACL09 0 P-1 150 8.6375 9.1639 12.5921 80.833 79.981 90.087 968.531 1.784 5-Fluorouracil No Co-ordinates FURACL10 0 P-1 298 8.7651 9.172 12.5826 81.021 80.483 88.966 985.38 1.754 5-Fluorouracil No Co-ordinates FURACL11 0 P-1 298 8.7683 9.18 12.6971 81.394 80.783 89.059 997.443 1.732 5-Fluorouracil No Co-ordinates FURACL12 0 P-1 150 8.6328 9.1668 12.5987 80.96 80.041 90.09 969.356 1.783 5-Fluorouracil No Co-ordinates FURACL13 0 P-1 150 8.653 9.157 12.632 80.56 79.813 89.973 971.364 1.779 5-Fluorouracil No Co-ordinates FUREHX 5.5 P21/c 295 4.656 15.276 17.807 90 90.8 90 1266.4 1.543 5-Fluorouracil-9-ethylhypoxanthine FURMCY 9.4 Pbca 295 18.35 11.4 10.26 90 90 90 2146.289 1.58 5-Fluorouracil-1-methylcytosine complex GAGTAK 3.5 P212121 180 10.6496 12.168 33.733 90 90 90 4371.268 1.284 5-(Ethisteron-21-yl)uracil GEHCIF 3.4 P21/n 295 8.755 16.549 16.319 90 91.97 90 2363.005 1.42 GONHOG 4 P2 1 295 5.387 12.495 8.638 90 103.2 90 566.067 1.641 Dicarbonyl-nitrosyl-(5- diphenylphosphinouracil-p)-cobalt methanol solvate Metal 1,4-Dideoxy-1,4-imino-1-beta-(5-uracilyl)-Llyxitol hydrochloride 2

HONRAD 5.1 P21 295 5.508 12.113 8.551 90 104.85 90 551.454 1.588 1,2,4-Trideoxy-1-(2,4-dioxo-1,2,3,4- tetrahydropyrimidin-5-yl)-1,4-imino-alpha-lthreo-pentitol hydrochloride 1,2,4-Trideoxy-1-(2,4-dioxo-1,2,3,4- tetrahydropyrimidin-5-yl)-1,4-imino-l-threopentitol hydrochloride HONRAE 5 P212121 295 6.596 31.0674 5.425 90 90 90 1111.694 1.575 IURACL10 4.4 P2 1 295 14.21 4.458 4.899 90 92.31 90 310.091 2.549 5-Iodouracil (1,2-bis(Amidino-O-methylurea)ethane)- copper(ii) thymine bis(tetrafluoroborate) monohydrate Metal IVOROA 5.63 P-1 150 10.7999 11.3654 11.8496 116.093 92.31 106.55 1228.744 1.729 JEFWAT 3.69 C2/c 150 19.3785 5.9918 20.0293 90 117.813 90 2056.974 1.68 5-Fluoropyrimidine-2,4(1H,3H)-dione JEFWAT01 5.64 C2/c 298 19.856 5.946 20.073 90 117.66 90 2099.058 1.646 5-Fluoropyrimidine-2,4(1H,3H)-dione Higher R Higher T JEFWAT02 4.15 C2/c 150 19.235 5.9683 20.042 90 118.216 90 2027.423 1.705 5-Fluoropyrimidine-2,4(1H,3H)-dione Higher R JESMAW 6.88 P2 1/n 298 8.3535 6.4277 15.703 90 101.81 90 825.305 1.619 5-Nitrouracil hemikis(dioxane) JESMEA 6.36 P-1 298 4.3579 9.8014 12.731 94.712 99.452 97.603 528.678 1.528 5-Nitrouracil piperazine 5-Nitrouracil hemikis(n,n'- dimethylpiperazine) JESMIE 14.09 P-1 298 7.1052 7.601 10.15 93.023 106.631 117.689 453.807 1.567 JESMOK 4.74 P2 1/c 298 7.5173 12.7817 10.8938 90 97.78 90 1037.084 1.513 5-Nitrouracil pyridine JESMUQ 4.39 P2 1/c 298 14.1865 11.584 12.7907 90 94.775 90 2094.682 1.568 5-Nitrouracil bis(formamide) JESNAX 7.54 P2 1/c 293 11.8264 11.8738 12.6511 90 98.696 90 1756.1 1.605 5-Nitrouracil ethanol hemihydrate JESNEB 12.35 P2 1/c 298 8.2825 4.9546 25.608 90 98.293 90 1039.874 1.611 5-Nitrouracil 3-aminopyridine 5-Nitrouracil 1,4-diazabicyclo(2.2.2)octane JESNIF 5.84 P2 1/c 293 9.2323 9.6598 32.2899 90 90.801 90 2879.402 1.45 hydrate KEWJUS 6.17 P2 1 293 10.3388 5.1216 15.23 90 94.85 90 803.559 1.489 Malayamycin A monohydrate LAFTOC 3.39 P2 1/m 293 5.3645 20.558 8.2 90 93.954 90 902.171 2.191 LAFTUI 3.39 P2 1/m 293 5.384 20.684 8.23 90 93.454 90 914.85 2.212 LAFVAQ 4.83 P-1 293 10.239 12.902 13.342 61.364 89.874 71.341 1441.221 1.778 LAFVEU 4.95 C2/c 293 17.111 14.495 13.137 90 99.57 90 3212.946 1.773 Tetra-aqua-bis(1,2,3,4-tetrahydro-2,4-dioxo- 5-pyrimidinecarboxylato)-terbium(iii) trihydrate Metal Tetra-aqua-bis(1,2,3,4-tetrahydro-2,4-dioxo- 5-pyrimidinecarboxylato)-ytterbium(iii) trihydrate Metal (mu!2$-1,2,3,4-tetrahydro-2,4-dioxo-5- pyrimidinecarboxylato)-diaqua- tetrakis(1,2,3,4-tetrahydro-2,4-dioxo-5- pyrimidinecarboxylato)-bis(1,10- phenanthroline)-di-praseodymium(iii) pentahydrate Metal bis((1,2,3,4-tetrahydro-2,4-dioxo-5- pyrimidinecarboxylato)-(1,10- phenanthroline))-europium(iii) dihydrate Metal 3

LAFVIY 4.31 C2/c 293 17.156 14.486 13.218 90 100.216 90 3232.882 1.776 LAFVOE 2.54 C2/c 293 17.142 14.341 13.267 90 101.633 90 3194.479 1.827 LICCEG 2.97 P-1 296 8.8127 11.5868 13.5365 81.433 77.957 73.665 1291.221 1.841 LUXHIV 7.27 P2 1/n 293 7.275 25.739 16.352 90 95.5 90 3047.836 1.858 bis((1,2,3,4-tetrahydro-2,4-dioxo-5- pyrimidinecarboxylato)-(1,10- phenanthroline))-terbium(iii) dihydrate Metal bis((1,2,3,4-tetrahydro-2,4-dioxo-5- pyrimidinecarboxylato)-(1,10- phenanthroline))-ytterbium(iii) dihydrate Metal trans-diaqua-(5,5'-((e,e)-pyridine-2,6-diyl- bis(methylidynenitrilo))-bis(pyrimidine- 2,4(1H,3H)-dione))-zinc(ii) nitrate hexafluorophosphatetrihydrate Metal catena-((μ2-perchlorato-o,o')-(6-(4',6'- diamino-1',3',5'-triazinyl)-1,4,6,8,11-pentaazacyclotetradecane)-copper(ii) thymine diperchlorate trihydrate) Metal fac,cis-chloro-(n,n- bis(diphenylphosphinoethyl)propylamino)-(1- (5-aminouracil-N,O)-2-phenylethylidene)- ruthenium(ii) chloride methanolsolvate monohydrate Metal MIRPAE 4.55 P2 1/n 293 15.682 14.273 19.748 90 102.79 90 4310.505 1.441 NIMFOE 3.63 P2 1/n 295 5.873 9.693 10.4561 90 104.07 90 577.377 1.807 5-Nitrouracil NIMFOE01 7.81 Pbca 130 8.308 10.426 13.363 90 90 90 1157.492 1.803 5-Nitrouracil NIMFOE02 7.59 P2 12121 130 5.4342 9.8406 10.3659 90 90 90 554.325 1.882 5-Nitrouracil NIMGAR 2.97 P2 1/n 295 8.858 6.9619 15.822 90 95.823 90 970.685 1.61 5-Nitrouracil dimethyl sulfoxide solvate NIMGAR01 3.3 P2 1/n 298 8.8723 6.97 15.8489 90 95.876 90 974.945 1.602 5-Nitrouracil dimethylsulfoxide Higher R NURAMH 6 P2 1/c 295 5.137 21.956 9.587 90 143.5 90 643.181 1.808 5-Nitrouracil monohydrate Diaqua-bis(2,4-dioxopyrimidin-5- carboxylato)-copper(ii) PABREQ 7.36 P2 1/n 293 5.0497 10.0186 13.715 90 96.237 90 689.748 1.973 PAHHOW 5.21 P-1 150 7.0847 8.4733 10.2291 98.128 96.913 99.785 592.451 1.705 5-Fluorouracil 1,4-dioxane PAHHUC 4.85 P2 1/n 150 14.7361 5.8693 16.397 90 100.524 90 1394.33 1.588 5-Fluorouracil dimethylformamide PAHJAK 3.63 P2 1/c 150 9.8831 10.8128 8.6842 90 107.397 90 885.576 1.562 5-Fluorouracil dimethylsulfoxide PAHJAK01 0 P2 1/c 298 8.8509 10.8777 10.0346 90 108.096 90 918.319 1.506 5-Fluorouracil dimethylsulfoxide No Co-ordinates QARWAI 4.09 P-1 150 4.6195 7.0493 7.3452 88.169 81.504 86.245 235.998 1.803 5-Hydroxyuracil QARWEM 0 Pna2 1 295 44.7907 6.8253 8.8082 90 90 90 2692.755 1.649 5-Hydroxyuracil dimethylsulfoxide solvate No Co-ordinates 5-beta-D-Ribofuranosyl-2,4(1H,3H)- ROKYUL 9.18 P1 295 5.1318 6.9156 14.9166 83.3087 88.388 71.835 499.554 1.623 pyrimidinedione 5-(1-(3-Methoxycarbonyl-Oethylpseudoureido))uracil SABNOY 4.1 C2/c 295 16.964 10.375 13.533 90 100.2 90 2344.185 1.452 5-(1-(3-Methoxycarbonyl-Sethylpseudothioureido))uracil SABNUE 3.4 P21/n 295 10.685 11.058 11.557 90 113.12 90 1255.842 1.44 4

Potassium (N,N'-bis(acetato)-N,N'-bis(N''- uracil-5-ylacetamido)-1,2-ethylenediamine)- SOQZUT 5.8 P21/n 295 6.5402 25.967 16.6431 90 91.718 90 2825.217 1.694 dioxo-vanadiumpentahydrate Metal (N,N'-bis(Acetato)-N,N'-bis(N''-uracil-5- ylacetamido)-1,2- SORBOQ 5.7 C2/c 295 11.475 9.7093 22.62 90 94.12 90 2513.677 1.754 ethylenediamine)-aqua-zinc tetrahydrate Metal Diaqua bis(1,2,3,4-tetrahydro-2,4-dioxo-5- TAGVOM 3.31 P2 1/n 295 5.0615 10.118 13.812 90 95.67 90 703.883 1.893 pyrimidinecarboxylato)-manganese(ii) Metal THYBNZ10 8.4 Pcmn 295 12.427 12.639 6.859 90 90 90 1077.308 1.444 Thymine-p-benzoquinone complex THYMEL 0 P21/c 295 7.167 16.123 13.179 90 104.2 90 1476.349 0 Thymine N,N-diethylmelamine monohydrate No Co-ordinates THYMIN 14.9 P2 1/c 295 12.87 6.83 6.7 90 105 90 568.876 1.473 Thymine Higher R No H THYMIN01 4.58 P2 1/c 295 12.889 6.852 6.784 90 104.92 90 578.933 1.447 Thymine THYMMH 7.8 P2 1/c 295 6.077 27.862 3.816 90 94.32 90 644.279 1.486 Thymine monohydrate TUGMEN 5.33 P2 1 233 5.989 6.819 12.419 90 90 90 507.179 1.599 5-(beta-D-Arabinofuranosyl)uracil No Co-ordinates UGUMUE 4.94 R-3 213 25.5695 25.5695 5.1934 90 90 120 2940.539 1.831 5-(Trifluoromethyl)uracil URACIL 4.5 P21/a 295 11.938 12.376 3.6552 90 120.9 90 463.386 1.607 Uracil URACIL01 3.5 P2 1/a 295 11.938 12.376 3.6552 90 120.9 90 463.386 1.607 Uracil No Co-ordinates URILHG 9.3 P-1 295 6.898 3.951 11.835 88.57 101.44 87.03 315.514 2.609 bis(uracil) mercury(ii) chloride complex Metal catena-((μ2-aqua)-(μ2-5-carboxyuracil)- lithium) Metal VEYVUQ 3.09 P2 1/n 295 3.521 18.146 10.335 90 90.82 90 660.257 1.811 catena-((μ2-5-uracilmethyl hydrogen phosphonato)-bis(μ2-aqua)-diaqua-sodium WASSOZ 4.74 P-1 293 6.385 9.404 10.841 83.01 78.46 71.74 604.449 1.748 monohydrate) Metal catena-(bis(μ2-5-uracilmethyl hydrogen phosphato)-tris(μ2-aqua)-diaqua-dipotassium) WASSUF 4.28 C2/c 293 16.906 6.626 20.654 90 104.89 90 2235.954 1.718 Metal WESRAN 6 P2 1/c 295 5.067 15.072 11.239 90 125.8 90 696.153 1.963 bis(6-carboxyuracil)-diaqua-zinc(ii) Metal WEWTAU 3.1 P-1 287 9.804 12.411 13.73 90.4 100.11 90.65 1644.517 1.598 WUYGIG 2.66 P2 1/c 295 9.077 9.444 15.499 90 101.76 90 1300.736 1.939 WUYGOM 5.77 P2 1/c 295 9.035 9.888 15.83 90 101.23 90 1387.144 1.885 WUYGUS 7.9 P2 1/c 295 15.696 13.236 7.515 90 94.49 90 1556.467 1.924 XOJXID 5.2 P-1 295 10.866 9.42 8.337 83.91 83.8 110.46 785.312 1.923 Chloro-bis(1,10-phenanthroline)-copper(ii) bis(5-fluorouracil) chloride dihydrate Metal Dichloro-(5-formyluracil N- methylthiosemicarbazone-n,o,s)- copper(ii)monohydrate Metal Dichloro-(5-formyluracil N,N- dimethylthiosemicarbazone-n,o,s)- copper(ii)monohydrate Metal Diaqua-(5-formyluracil N- methylthiosemicarbazone-n,o,s)-(nitrato- O)-copper(ii) nitrate Metal Diaqua-(5-formyluracil thiosemicarbazone- N,O,S)-copperdinitrate monohydrate Metal 5

XOJXOJ 6.8 P21/c 295 16.345 12.967 6.756 90 92.4 90 1430.649 1.843 Diaqua-chloro-(5-formyluracil thiosemicarbazone-n,o,s)-nickel chloride monohydrate Metal bis(bis(5-formyluracil thiosemicarbazonato- N,O,S)-cobalt(iii)) sulphate pentahydrate Metal XOJXUP 7.2 C2/c 295 7.372 26.709 21.958 90 90.49 90 4323.345 1.771 YAZRAS 3.35 P-1 295 7.76 8.121 10.045 73.47 83.99 64.7 548.55 1.778 bis(dithiobiureto)-nickel(ii) di-uracil dihydrate Metal bis(3,7-dihydro-1,3-dimethyl-1h-purine-2,6- dione) 5-fluoro-2,4(1H,3H)-pyrimidinedione monohydrate ZAYLOA 5.9 P21/c 295 7.64 8.804 32.126 90 98.28 90 2138.352 1.579 ZUNYIQ 7.8 P-1 295 5.036 9.626 8.128 74.65 88.96 84.65 378.297 1.923 Diaqua-bis(iso-orotato)-iron dihydrate Metal 6

Table S1.2 Motif analysis of the 49 compounds in the CSD which fitted the search criteria Refcode S. G. Z Z' Uracil Co-crystallizer Motif Further Notes GAGTAK P212121 8 2 5-Ethisteron-21-yl Dimers N3(H) O2 dimers; N1(H) interacts with R ADOSBU P21 2 1 Br Adenosine No interactions with itself All interactions to adenosine BRURAC10 P21/c 4 1 Br Symmetric ribbon (disorder not modelled) UGUMUE R-3 18 1 CF3 3-D N2(H) O2 dimers linked by N1(H) O1; have CF3 rich regions BOMMOF P-1 2 1 CH2PPh3 EtOH Dimers N3(H) O1 dimers; Discrete CLURAC10 P21/c 4 1 Cl Symmetric ribbon (disorder not modelled) AYEBIP P21/c 8 2 COOH H2O Dimers N3(H) O2 dimers; linked by N1(H) O(COOH) into herringbone sheet ZAYLOA P21/c 4 1 F Theophylline, H2O No interactions with itself linked into chains by H2O (N1/O2); N3(H) O1 links to theophylline BIKHIN01 P21 2 1 F TFE Symmetric ribbon Parallel polar (TFE interdigitates) JEFWAT C2/c 16 2 F Me 3-D N2(H) O2 dimers linked by N1(H) O1 single PAHJAK P21/c 4 1 F DMSO No interactions with itself All interactions to DMSO; chains with DMSO PAHHUC P21/n 4 1 F DMF 4,4-grid N3(H) O2 dimers (M1); linked by M2 into 4,4-grids (dimers = nodes) PAHHOW P-1 1 0.5 F Dioxane Chains N3(H) O2 dimers and N3(H) O1 dimers linked into chains by N1(H) O1 singles CYTFUR01 P-1 2 1 F Cytosine, H2O Dimers Asymmetric ribbon N3(H) O2 dimers; N1(H) O1 dimers with cytosine link 5FU dimers into FUREHX P21/c 4 1 F 9-Ethylpoxanthine Dimers N3(H) O2 dimers; linked by O1 X into 4,4-grid (dimers = nodes) N3(H) O2 dimers; N1(H) O1 interactions with Mcy into mini (4) asymmetric ribbon FURMCY Pbca 8 1 F 1-Methylcytosine Dimers FURACL01 P-1 8 4 F 4.8 2 net N2(H) O2 dimers; N1(H) O1 single; F regions FURACL03 P21/c 4 1 F Asymmetric ribbon Sheets URACIL P21/a 4 1 H 6,3 net brickwall N3(H) O2 dimers; N1(H) O2 single; Also C5(H) O1 to make dimers IURACL10 P21 2 1 I 4,4-grid N1(H) O1 single; N2(H) O1 single; HONRAE P212121 4 1 L-Penitol HCl Symmetric ribbon Anti-parallel polar GONHOG P21 2 1 Lyxitol HCl Chains N1(H) O2 interactions KEWJUS P21 2 1 Malamycin H2O 4,4-grid N1(H) O1 + N3(H) O2 single interactions THYMMH P21/c 4 1 Me H2O Symmetric ribbon Anti-parallel non-polar THYBNZ10 Pcmn 4 0.5 Me Benzoquinone Symmetric ribbon Parallel polar THYMIN01 P21/c 4 1 Me Symmetric ribbon Parallel polar SABNOY C2/c 8 1 NHC(OEt)NCOOMe Symmetric ribbon Parallel non-polar SABNUE P21/n 4 1 NHC(SEt)NCOOMe 6,3 net brickwall N3(H) O1 dimers; N1(H) O2 singles JESMOK P21/c 4 1 NO2 Pyridine Chains N1(H) O2 + O(NO2) interactions JESMEA P-1 2 1 NO2 Piperazine Dimers N3(H) O2 dimers; N1(H) + ppz into chains NURAMH P21/c 4 1 NO2 H2O Dimers N3(H) O2 dimers; H2O O2 link dimers into chains (H2O NO2 - sheets) JESMUQ P21/c 8 2 NO2 Formamide No interactions with itself All interactions to formamide 7

JESNAX P21/c 8 2 NO2 EtOH, H2O Dimers N3(H) O2 dimers, discrete (mol1); also chains with EtOH (mol2) NIMGAR P21/n 4 1 NO2 DMSO No interactions with itself All interactions to DMSO; chains with DMSO (cf F case) JESMAW P21/n 4 1 NO2 Dioxane 6,3 net herringbone N1(H) O1 dimers; N3(H) O2 singles JESMIE P-1 2 1 NO2 Dimethylpiperazine Dimers N3(H) O1 dimers; Other bits link dimers JESNIF P21/c 8 2 NO2 DABCO, H2O Dimers N3(H) O2 dimers; Other bits link dimers JESNEB P21/c 4 1 NO2 3-Aminopyridine Dimers N3(H) O2 dimers; Other bits link dimers NIMFOE P21/n 4 1 NO2 Asymmetric ribbon Packs into zigzags NIMFOE01 Pbca 8 1 NO 2 Asymmetric ribbon Packs into zigzags NIMFOE02 P212121 4 1 NO 2 4,4-grid N1(H) O1 + N2(H) O2 (all single) QARWAI P-1 2 1 OH Symmetric ribbon Parallel non-polar FORHAV P21/c 4 1 PPh2 6,3 net brickwall N3(H) O1 dimers; N1(H) O2 singles HONRAD P21 2 1 a-penitol HCl Chains N1(H) O2 interactions N1(H) O1 dimers; linked by tails into chain. Also N3-Cl-tail interactions to 2-D BEBWIO C2/c 8 1 D-Penitol HCl, H2O Dimers APSURD P21 2 1 Psuedouridine H2O No interactions with itself All uracil to tail or H2O interactions ROKYUL P1 2 2 Psuedouridine Symmetric ribbon Parallel polar CYSURC10 P21 2 1 CH2SCH2C(COO)NH3 H2O Symmetric ribbon Parallel polar CYSTYM P212121 4 1 SCH 2C(COOH)NH3 HCl Chains N1(H) O1 interactions Table S1.3 Torsion angles between the NO2 and uracil groups in 5-nitrouracil crystal structures Refcode S. G. Z Z Co-crystallizer Angle O-N-C5-C4 ( ) JESMOK P21/c 4 1 Pyridine -3.42 JESMEA P-1 2 1 Piperazine -7.19 NURAMH P21/c 4 1 H2O -4.17 JESMUQ P21/c 8 2 Formamide -2.17; 9.02 JESNAX P21/c 8 2 EtOH, H2O 12.32; 3.99 NIMGAR P21/n 4 1 DMSO 15.61 JESMAW P21/n 4 1 Dioxane -0.96 JESMIE P-1 2 1 Dimethylpiperazine 19.16 JESNIF P21/c 8 2 DABCO, H2O -2.28; -3.34 JESNEB P21/c 4 1 3-Aminopyridine -3.44 NIMFOE P21/n 4 1-5.88 NIMFOE01 Pbca 8 1 3.50 NIMFOE02 P212121 4 1 3.54 8

2. Results of the searches for possible crystal structures All tables give just the unique, mechanically stable structures found within 5 kj mol -1 of the global minimum in lattice energy, except 5-fluorouracil where 6 kj mol -1 are given and 5-nitrouracil where the lowest 10 kj mol -1 are listed. The unit cell parameters of the experimental crystal structure(s) are given in the first shaded row(s), indicated by the CSD refcode if available or compound name for new structures, in the same unit cell setting as the corresponding structure found in the search (either the experimental structure or the search structure may have been transformed using PLATON such that the two structures are in the same setting). The structure(s) found in the search which correspond to the known form(s) are highlighted in bold text. The hypothetical crystal structures are stored on the STFC e-science Centre dataportal and are available in.res format from the authors on request. Searches were performed on both conformational possibilities of 5-vinyluracil since the conformational energy difference is only 2.21 kj mol -1. (a) (b) Figure S2.1 The two conformations of 5-vinyluracil considered (a) with the vinyl group on the same side as the carbonyl and (b) with the vinyl group on the opposite side to the carbonyl. The torsion angles ( ) are given in green (C - dark grey; H - light grey; N - blue; O - red). Two searches were also performed on nitrouracil one with the gas phase ab initio optimized conformation with a torsion angle for C4 C5 N1 O3 of 27.75 and one with the NO2 group constrained to be in the same plane as the uracil. 9

(a) (b) Figure S2.2 The two conformations of 5-nitrouracil considered (a) the gas phase ab initio optimized conformation and (b) with the NO2 group constrained to be in the same plane as the uracil. The torsion angles ( ) are given in green (C - dark grey; H - light grey; N - blue; O - red). Table S2.1 The low energy structures found for uracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L.E. (kj mol -1 ) Motif Analysis URACIL P21/c 4 3.6552 12.3760 10.3110 90 96.570 90 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat da12 Cc 2 6.6066 10.9058 7.0789 90 111.009 90 1.5636-101.54 Sheets Symmetric Ribbon Polar Parallel Flat ai46 P21/c 4 9.7468 7.0032 7.1272 90 80.042 90 1.5537-101.52 Sheets Symmetric Ribbon Polar Parallel Flat cd105 P21 8 12.4027 10.9877 7.0209 90.184 90 90 1.5563-101.49 Sheets Symmetric Ribbon Polar Parallel Flat am100 P21/c 4 3.7186 10.5728 12.2815 90 92.556 90 1.5434-101.38 Sheets Asymmetric Ribbon Flat ca96 P-1 2 9.3421 6.3627 9.3897 108.157 140.285 48.400 1.5355-101.17 Sheets Symmetric Ribbon Non-Polar Parallel Flat am36 P21/n 4 3.6394 10.6236 12.5473 90 97.337 90 1.5473-100.99 Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates ca59 P-1 2 7.0149 6.7123 7.7671 111.304 126.735 99.310 1.5823-100.88 Sheets Symmetric Ribbon Non-Polar Parallel Flat ab72 P-1 2 5.3220 4.6871 10.2257 92.542 110.724 91.955 1.5641-100.87 Sheets Symmetric Ribbon Non-Polar Parallel Flat am10 P21/c 4 6.8884 10.9884 6.8452 90 65.272 90 1.5820-100.80 Sheets Symmetric Ribbon Non-Polar Parallel Flat aj39 P2/c 4 9.8920 6.9560 7.0756 90 79.535 90 1.5550-100.76 Sheets Symmetric Ribbon Non-Polar Parallel Flat cb99 Pbca 8 10.6126 14.6721 6.2772 90 90 90 1.5234-100.73 Sheets Asymmetric Ribbon Flat am2 P21/c 4 5.9747 10.5700 7.6554 90 94.067 90 1.5438-100.72 Sheets Asymmetric Ribbon Flat dc6 P-1 4 13.0084 3.7413 20.0335 100.478 84.442 85.862 1.5670-100.67 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ak38 P21/c 4 7.8756 7.0457 8.7365 90 97.609 90 1.5494-100.67 Sheets Symmetric Ribbon Polar Parallel Flat cb66 P21 8 12.6841 11.9732 6.8861 65.114 90 90 1.5696-100.58 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat fa23 P21 4 3.6843 21.4495 5.9944 90 90.408 90 1.5717-100.48 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ay96 P21 4 7.0043 11.0169 6.2272 90 90 89.821 1.5494-100.41 Sheets Symmetric Ribbon Polar Parallel Flat ab40 P-1 2 6.9773 3.8748 10.7975 98.018 101.108 55.917 1.5702-100.39 Sheets Symmetric Ribbon Non-Polar Parallel Stepped de95 C2/c 4 19.8019 6.9677 19.7258 90 20.812 90 1.5398-100.36 Sheets Symmetric Ribbon Polar Anti-Parallel Flat 10

am7 P21/c 4 3.7230 12.8037 10.0542 90 94.750 90 1.5588-100.32 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat dd16 P1 4 12.3665 4.0256 23.6847 113.838 115.866 67.745 1.5830-100.32 Sheets Asymmetric Ribbon Flat fa29 P21/c 4 6.2736 10.7539 8.9643 90 51.339 90 1.5765-100.32 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am81 P21/c 4 5.6765 11.5523 7.3464 90 82.860 90 1.5575-100.21 Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates fc82 P21/c 4 4.6288 5.2851 19.3506 90 93.723 90 1.5761-100.20 CrissCross Symmetric Ribbon Non-Polar cb100 Pca21 8 7.0087 6.9232 19.9723 90 90 90 1.5365-99.97 Sheets Symmetric Ribbon Polar Parallel Undulates dd49 C2/c 4 7.5099 6.9788 19.0214 90 105.793 90 1.5522-99.89 Sheets Symmetric Ribbon Polar Parallel Flat fc91 P21/c 4 5.8948 3.7187 21.8486 90 92.821 90 1.5563-99.85 CrissCross Symmetric Ribbon Non-Polar am82 P21/c 4 5.1891 12.6542 7.3286 90 94.648 90 1.5522-99.81 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat cd7 Pbcn 8 10.6742 6.8111 13.2782 90 90 90 1.5424-99.79 Sheets Asymmetric Ribbon Stepped cc34 P21 8 3.7296 12.8784 19.7555 90 90 86.098 1.5729-99.79 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates cc33 P21 8 3.7297 12.8785 19.7540 90 90 86.109 1.5729-99.77 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fa31 P21/c 4 3.7344 19.7345 6.8197 90 109.624 90 1.5727-99.76 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am65 P21/c 4 3.6072 13.4818 9.9866 90 89.964 90 1.5329-99.75 Sheets Asymmetric Ribbon Stepped av17 Pc 4 13.8947 9.9760 3.6676 90 73.704 90 1.5258-99.66 CrissCross Asymmetric Ribbon dc27 C2/c 4 12.8816 3.7273 22.1822 90 117.889 90 1.5818-99.66 CrissCross Symmetric Ribbon Non-Polar fa15 P21/c 4 3.6546 21.4864 7.0270 90 120.593 90 1.5674-99.57 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ap38 P1 4 10.7260 12.2663 3.7165 80.761 90 90 1.5426-99.43 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A au79 Pna21 4 21.7852 3.7101 5.9650 90 90 90 1.5442-99.43 CrissCross Symmetric Ribbon Polar cd1 Pbcn 8 11.1149 6.7688 12.6340 90 90 90 1.5665-99.42 Sheets Symmetric Ribbon Non-Polar Parallel Undulates ca17 P-1 2 4.8601 7.1831 7.1158 99.370 102.957 83.311 1.5639-99.38 Sheets Asymmetric Ribbon Flat cb64 P212121 8 11.6897 12.7518 6.4480 90 90 90 1.5492-99.32 Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates fc51 P21/n 4 4.2228 6.9896 16.4832 90 82.152 90 1.5448-99.29 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ab44 P-1 2 6.2182 9.4503 9.5338 141.756 108.956 49.429 1.5385-99.26 Sheets Asymmetric Ribbon Flat ad41 Pc 2 3.6929 10.9103 7.0458 90 122.071 90 1.5474-99.20 Sheets Symmetric Ribbon Non-Polar Parallel Undulates fc47 P21/n 4 4.7772 7.1791 13.8731 90 97.269 90 1.5774-99.18 Sheets 6,3-Net; Herringbone JESMAW Flat au19 Pna21 4 22.0147 5.9784 3.6869 90 90 90 1.5343-98.96 CrissCross Symmetric Ribbon Polar ak45 P21/c 4 8.9978 6.9624 7.7806 90 97.772 90 1.5416-98.93 Sheets Symmetric Ribbon Non-Polar Parallel Stepped fa50 P21/c 4 3.8890 20.5095 7.2378 90 125.775 90 1.5896-98.92 Sheets 6,3-Net; Herringbone JESMAW Undulates bf65 Pc 4 5.8344 21.9846 3.9172 69.272 90 90 1.5843-98.84 Sheets 6,3-Net; Herringbone O2 Dimer Undulates ce29 Pc 8 19.8196 3.9834 13.9929 90 90 118.874 1.5392-98.77 Sheets Symmetric Ribbon Non-Polar Parallel Stepped av8 Pna21 4 10.9708 11.0491 3.9579 90 90 90 1.5518-98.67 3-D be13 Pnn2 4 21.7996 5.9792 3.6805 90 90 90 1.5519-98.58 CrissCross Symmetric Ribbon Polar ay13 Pa 4 20.2947 3.8836 5.9211 90 90 90 1.5953-98.56 3-D 11

ak44 P21/c 4 IURACL10 9.3773 6.9819 7.7844 90 73.170 90 1.5262-98.56 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped af76 P21 2 4.0473 7.0005 8.6364 90 97.522 90 1.5345-98.55 Sheets Symmetric Ribbon Polar Parallel Stepped ak75 P21/c 4 10.1782 3.6672 12.8054 90 79.725 90 1.5830-98.45 Sheets 6,3-Net Free O2 Undulates dc53 C2/c 4 12.9416 3.6878 24.3538 90 54.952 90 1.5648-98.43 CrissCross Symmetric Ribbon Non-Polar aj30 P2/c 4 9.6683 7.1007 7.0864 90 101.700 90 1.5628-98.37 Sheets Asymmetric Ribbon Flat ai41 P21/c 4 11.0960 3.7060 12.8319 90 116.608 90 1.5780-98.35 Sheets 6,3-Net Free O2 Undulates am72 P21/c 4 3.7986 13.1562 9.5767 90 84.631 90 1.5625-98.31 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A cc2 Pbca 8 7.0304 6.5110 21.1269 90 90 90 1.5397-98.25 Sheets Symmetric Ribbon Polar Parallel Undulates am28 P21/c 4 3.6280 11.1384 12.3491 90 82.866 90 1.5036-98.15 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am75 P21/n 4 3.6655 11.0701 12.1432 90 92.515 90 1.5124-98.14 Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates am4 P21/n 4 3.6592 11.0551 12.1850 90 91.628 90 1.5110-98.12 Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates cc93 Pca21 8 3.7093 12.7795 19.9498 90 90 90 1.5745-98.12 Sheets 6,3-Net Free O2 Undulates da104 Cc 2 8.1479 11.2531 13.7549 90 157.804 90 1.5626-98.11 3-D cd86 Pbcn 8 13.3000 6.3249 11.6171 90 90 90 1.5237-97.87 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A cd81 P21 8 12.4756 12.6599 7.3629 122.162 90 90 1.5125-97.81 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A aq5 P21 4 11.7666 11.7422 3.6146 90 84.643 90 1.4973-97.78 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd87 C2/c 4 7.4871 7.0575 18.0043 90 99.956 90 1.5891-97.75 Sheets 6,3-Net; Herringbone JESMAW Flat ap78 P1 4 12.2424 11.4557 3.5711 101.546 90.004 89.936 1.5172-97.73 3-D de20 C2/c 4 19.8450 3.6548 23.0318 90 34.492 90 1.5740-97.73 Sheets 6,3-Net Free O2 Undulates ak15 P21/c 4 8.9260 7.0073 7.6515 90 80.562 90 1.5770-97.68 Sheets Asymmetric Ribbon Flat fc42 P21/n 4 3.8971 5.7762 20.8865 90 93.363 90 1.5862-97.58 Sheets 6,3-Net; Herringbone JESMAW Undulates de39 C2/c 4 22.7905 3.6634 12.8883 90 61.544 90 1.5739-97.48 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd102 P21 8 11.8315 12.6595 6.4773 90 90 89.995 1.5348-97.48 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat ar70 Pnn2 4 10.6075 13.4864 3.4901 90 90 90 1.4912-97.42 Sheets Asymmetric Ribbon Stepped ar11 Pnn2 4 12.2321 11.5373 3.5303 90 90 90 1.4943-97.41 3-D cb11 P1 8 7.1460 12.6185 12.8817 89.960 108.507 66.295 1.4928-97.31 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A af7 P21 2 3.7056 5.8483 11.3648 90 109.980 90 1.6082-97.17 Sheets 4,4-grid IURACL10 cb53 P1 8 12.7603 6.6933 12.6953 89.581 90.391 113.713 1.4999-97.13 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A fa87 P21/c 4 7.0018 18.3485 8.1112 90 28.186 90 1.5126-97.08 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc60 Pc 4 6.9972 4.1112 17.0136 90 88.324 90 1.5218-97.08 Sheets Symmetric Ribbon Non-Polar Parallel Undulates ad3 Pc 2 3.6004 10.1965 6.7577 90 107.995 90 1.5777-97.06 Sheets Symmetric Ribbon Polar Parallel Undulates av67 P1 4 12.9239 10.6542 3.5535 93.357 87.934 90.519 1.5252-96.93 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A av23 P1 4 12.9240 10.6540 3.5534 93.356 92.064 89.481 1.5253-96.93 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A aq73 P212121 4 5.8853 21.3573 3.6811 90 90 90 1.6091-96.92 Sheets 4,4-grid 12

ak16 P21/c 4 8.9955 6.9988 7.7220 90 74.543 90 1.5888-96.89 Sheets 6,3-Net; Herringbone JESMAW Flat fc90 P21/c 4 6.0570 3.7062 21.1473 90 85.837 90 1.5724-96.88 Sheets 6,3-Net; Herringbone O2 Dimer Undulates bb19 P21 4 16.5293 7.0136 4.2234 90 90 90 1.5206-96.88 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates av62 Pna21 4 11.2053 12.0662 3.5952 90 90 90 1.5316-96.87 3-D bb55 P21 4 21.0338 4.1470 5.3667 90 90 90 1.5904-96.87 3-D aj1 P-1 4 10.7024 3.5760 12.8485 82.964 90.200 78.265 1.5588-96.84 Sheets Symmetric Ribbon Non-Polar Parallel Undulates ce45 Pbcn 8 21.1107 6.9747 6.5994 90 90 90 1.5324-96.84 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates av40 Pna21 4 8.3034 11.1566 5.3104 90 90 90 1.5134-96.79 3-D bd56 Pna21 4 20.7649 6.0376 3.7459 90 90 90 1.5853-96.73 3-D fc79 P21/c 4 5.8202 3.9480 20.8088 90 78.924 90 1.5866-96.73 Sheets 6,3-Net; Herringbone JESMAW Flat de82 C2/c 4 22.9817 3.7286 12.1872 90 66.358 90 1.5565-96.70 Sheets 6,3-Net; Herringbone JESMAW Flat fc5 P21/c 4 3.6643 5.9288 22.0499 90 104.179 90 1.6030-96.69 Sheets 4,4-grid IURACL10 fc35 P21/n 4 3.6830 5.8621 21.7216 90 82.104 90 1.6027-96.69 Sheets 4,4-grid IURACL10 bh24 Pa 4 18.0831 3.8969 7.0133 90 90 90 1.5064-96.69 Sheets Symmetric Ribbon Polar Parallel Undulates 13

THYMIN01 cc90 ce5 ai19 de102 dc10 dd1 fa64 ak30 al20 ca90 ca92 cc27 ca136 Label P21/c Pbca Pbcn P21/c C2/c C2/c C2/c P21 P21/c P2/c P-1 P-1 Pbca P-1 S. G. Table S2.2 4 8 8 4 4 4 4 4 4 4 2 2 8 2 Z 12.889 7.0283 24.9658 13.0750 28.2849 21.0786 24.6770 3.8940 9.8744 12.7961 5.2170 4.7863 7.0281 3.8926 a(å) 6.852 6.6600 7.0357 7.0253 7.0347 7.0289 7.0133 25.4019 7.1304 7.0192 7.0228 5.2205 6.3299 5.9231 b(å) α( ) β( ) γ( ) 6.784 90 104.92 90 24.9140 90 90 90 6.6355 90 90 90 6.5942 90 105.017 90 26.0210 90 166.942 90 21.2204 90 22.140 90 25.3923 90 164.430 90 5.8712 90 90.068 90 8.2129 90 93.418 90 24.8144 90 164.642 90 11.9912 105.900 73.941 136.868 12.0180 105.899 95.842 90.970 26.6238 90 90 90 13.3453 70.606 84.979 89.323 c(å) The low energy structures found for thymine 1.4366 1.4374 1.4318 1.4322 1.4139 1.4203 1.4424 1.4512 1.4191 1.4598 1.4594 1.4145 1.4489-104.23-104.15-103.94-103.91-103.65-103.60-103.55-103.47-103.42-103.37-103.27-103.24-103.23 L. E. Density (g cm-3) (kj mol-1) Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Sheets Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Symmetric Ribbon Polar Polar Non-Polar Polar Non-Polar Polar Polar Non-Polar Polar Non-Polar Non-Polar Non-Polar Polar Non-Polar Motif Analysis Parallel Parallel Anti-Parallel Parallel Anti-Parallel Parallel Anti-Parallel Anti-Parallel Parallel Parallel Parallel Parallel Parallel Parallel 14 Stepped Undulates Undulates Stepped Stepped Stepped Stepped Undulates Stepped Stepped Stepped Stepped Stepped Flat (a) (b) Figure S2.3 Two alternative 6,3-nets observed for the theoretical crystal structures (a) ak75 from the uracil search with uncoordinated O2 and (b) bf65 from the uracil search (C - dark grey; H - light grey; N - blue; O - red).

dc19 C2/c 4 7.4042 7.0401 24.7233 90 63.539 90 1.4521-103.20 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped aj11 P2/c 4 11.1247 7.0286 7.7601 90 101.833 90 1.4105-103.10 Sheets Symmetric Ribbon Non-Polar Parallel Stepped dd37 C2/c 4 7.3985 7.0405 22.4464 90 99.212 90 1.4516-103.10 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ad53 Pc 2 3.8846 13.0007 7.0342 90 124.724 90 1.4345-102.87 Sheets Symmetric Ribbon Polar Parallel Flat fa7 P21/c 4 4.0752 25.4015 6.9977 90 126.567 90 1.4398-102.84 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates au9 Pna21 4 25.8063 3.8873 5.8297 90 90 90 1.4323-102.81 CrissCross Symmetric Ribbon Polar ca24 P-1 2 8.8168 6.3687 8.7930 85.766 124.283 127.926 1.4326-102.81 Sheets Symmetric Ribbon Non-Polar Parallel Flat bj91 P21 4 25.3772 3.9813 5.7690 90 90 90.063 1.4371-102.79 CrissCross Symmetric Ribbon Polar bg101 Pc 4 25.9812 7.0284 3.8946 55.123 90 90 1.4358-102.79 Sheets Symmetric Ribbon Polar Anti-Parallel Undulating ba88 P21 4 25.6989 7.0220 3.9568 125.224 90 90 1.4361-102.72 Sheets Symmetric Ribbon Polar Anti-Parallel Undulating bj34 P1121 4 22.9574 4.9784 5.0358 90 90 84.203 1.4629-102.71 CrissCross Symmetric Ribbon Polar be13 Pc 4 25.8776 5.8555 3.8627 90 90 90 1.4312-102.68 CrissCross Symmetric Ribbon Polar dd58 C2/c 4 7.0517 7.1614 22.9915 90 89.751 90 1.4429-102.61 Sheets Symmetric Ribbon Non-Polar Parallel Undulates da63 Cc 2 13.0998 12.5949 7.0789 90 150.466 90 1.4549-102.54 Sheets Symmetric Ribbon Polar Parallel Flat dd57 C2/c 4 7.0521 7.1539 24.0452 90 106.799 90 1.4426-102.49 Sheets Symmetric Ribbon Non-Polar Parallel Undulates cb117 Pca21 8 7.0588 12.9843 12.5901 90 90 90 1.4518-102.36 Sheets Symmetric Ribbon Polar Parallel Flat aq7 P212121 4 6.5243 12.5578 7.0585 90 90 90 1.4485-102.27 Sheets Symmetric Ribbon Polar Parallel Flat ce64 Pbcn 8 26.9597 7.0110 6.3654 90 90 90 1.3925-102.10 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates aj71 P-1 4 10.5630 4.0091 18.8238 120.945 91.687 61.052 1.4641-101.92 Sheets Asymmetric Ribbon Stepped db37 C2 2 7.3332 7.0785 11.2650 90 98.619 90 1.4489-101.64 Sheets Symmetric Ribbon Polar Parallel Stepped cc51 Pca21 8 5.2084 11.8955 18.3619 90 90 90 1.4726-101.63 Sheets 6,3-Net Free O2 Undulates am8 P21/c 4 7.0979 12.5859 7.7742 90 55.923 90 1.4562-101.39 Sheets Symmetric Ribbon Non-Polar Parallel Flat ai115 P21/c 4 10.4272 5.0877 11.8837 90 114.349 90 1.4584-101.34 Sheets 6,3-Net Free O2 Undulates fa1 P21/c 4 7.0076 20.3631 5.8882 90 46.067 90 1.3844-101.30 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates av11 P21 4 6.5961 12.5823 7.0686 90 90 89.903 1.4279-101.28 Sheets Symmetric Ribbon Polar Parallel Flat ak38 P21/c 4 8.2286 7.0382 12.1574 90 55.878 90 1.4371-101.07 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped ai81 P21/c 4 11.6082 3.9530 12.6721 90 101.760 90 1.4714-100.72 Sheets 6,3-Net Free O2 Undulates ab65 P-1 2 6.8529 9.5502 7.9015 139.425 67.500 121.687 1.4640-100.71 Sheets Asymmetric Ribbon Stepped dd8 C2/c 4 13.3493 3.9503 24.4530 90 66.529 90 1.4164-100.71 CrissCross Symmetric Ribbon Non-Polar fc123 P21/c 4 6.3156 7.0017 13.6865 90 76.092 90 1.4259-100.41 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped dd10 C2/c 4 13.0938 6.5528 18.8749 90 47.759 90 1.3973-100.38 Sheets Symmetric Ribbon Non-Polar Parallel Flat ak104 P21/c 4 14.3574 3.8879 12.7478 90 126.392 90 1.4624-100.12 Sheets 6,3-Net Free O2 Undulates am7 P21/c 4 6.0039 13.6477 7.3764 90 97.552 90 1.3980-100.07 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A al76 Pc 4 9.7903 3.9151 15.7896 90 73.993 90 1.4399-100.05 CrissCross Asymmetric Ribbon 15

fa103 P21/c 4 5.4061 27.5534 4.1814 90 87.521 90 1.3462-99.97 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ak41 P21/c 4 8.0679 6.9766 13.0868 90 126.665 90 1.4177-99.93 Sheets Symmetric Ribbon Polar Anti-Parallel Flat dd42 C2/c 4 6.9859 6.5441 26.6237 90 104.505 90 1.4218-99.66 Sheets Symmetric Ribbon Non-Polar Parallel Undulates am5 P21/c 4 3.9662 11.1650 13.2241 90 90.410 90 1.4305-99.66 Sheets 6,3-Net; Brickwall FORHAV Undulating No free D or A ai92 P21/c 4 9.6224 5.1811 11.7858 90 80.230 90 1.4466-99.61 Sheets 6,3-Net Free O2 Undulates db32 C2 2 6.9948 6.5175 14.8185 90 61.056 90 1.4169-99.52 Sheets Symmetric Ribbon Non-Polar Parallel Undulates db31 C2 2 6.9951 6.5131 14.8312 90 61.070 90 1.4164-99.50 Sheets Symmetric Ribbon Non-Polar Parallel Undulates dd124 C2/c 4 12.8503 5.4652 18.0561 90 72.467 90 1.3855-99.44 CrissCross Symmetric Ribbon Non-Polar Table S2.3 The low energy structures found for 5-ethyluracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analyisis 5-Ethyl P-1 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab24 P-1 2 7.6033 7.0668 9.8551 136.776 98.264 97.851 1.3878-109.14 Sheets Symmetric Ribbon Non-Polar Parallel Flat ab38 P-1 2 7.0666 9.6473 9.8547 130.327 43.224 128.658 1.3879-109.14 Sheets Symmetric Ribbon Non-Polar Parallel Flat dd88 C2/c 4 14.2901 6.7172 18.4950 90 49.083 90 1.3877-109.12 Sheets Symmetric Ribbon Non-Polar Parallel Flat ak6 P21/c 4 6.6488 7.0609 15.9134 90 114.678 90 1.3712-108.71 Sheets Symmetric Ribbon Polar Parallel Flat ca106 P-1 2 4.2400 5.7212 14.3039 98.768 100.353 92.650 1.3836-108.44 Sheets Symmetric Ribbon Non-Polar Parallel Stepped fc18 P21/c 4 6.9872 6.9301 14.1849 90 101.564 90 1.3833-108.08 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc22 P21/n 4 5.5510 4.2965 27.9431 90 87.682 90 1.3979-107.56 CrissCross Symmetric Ribbon Non-Polar fa44 P21/c 4 4.2452 28.3145 6.9196 90 125.420 90 1.3733-107.37 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc78 P21/n 4 8.0084 7.0112 12.3249 90 100.856 90 1.3696-107.27 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat am44 P21/c 4 4.7467 10.7710 13.1195 90 94.190 90 1.3915-107.13 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am85 P21/c 4 6.3532 14.6558 7.2356 90 102.908 90 1.4175-107.13 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A dd6 C2/c 4 7.3509 7.0215 28.7497 90 112.740 90 1.3603-106.94 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc76 P21/n 4 4.3126 5.5072 28.2928 90 92.085 90 1.3862-106.90 CrissCross Symmetric Ribbon Non-Polar ab107 P-1 2 7.0265 10.8428 8.9524 145.861 89.498 103.797 1.3345-106.74 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ai90 P21/c 4 13.3580 6.9583 7.5597 90 94.645 90 1.3291-106.53 Sheets Symmetric Ribbon Polar Parallel Stepped ca86 P-1 2 9.6700 5.5338 8.7188 93.055 123.817 111.265 1.3646-106.33 Sheets Asymmetric Ribbon Stepped dd101 C2/c 4 12.7139 6.0522 18.2137 90 89.517 90 1.3284-106.00 CrissCross Symmetric Ribbon Non-Polar dc64 C2/c 4 21.2193 7.0149 10.9606 90 121.055 90 1.3320-106.00 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fa71 P21/c 4 4.0860 28.2342 6.9771 90 122.689 90 1.3741-105.89 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates ca103 P-1 2 4.0873 6.1922 13.7828 88.640 86.921 82.280 1.3486-105.78 Sheets Symmetric Ribbon Non-Polar Parallel Stepped cc38 Pbca 8 6.9752 7.4587 27.0822 90 90 90 1.3213-105.62 Sheets Symmetric Ribbon Polar Parallel Undulates 16

ab72 P-1 2 9.6407 4.4210 9.8928 83.574 80.477 55.102 1.3649-105.32 Sheets Asymmetric Ribbon Stepped dd42 C2/c 4 7.3553 6.9929 27.3749 90 97.079 90 1.3323-105.32 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped da63 Cc 2 7.1067 14.5808 7.0153 90 106.766 90 1.3373-105.32 Sheets Symmetric Ribbon Polar Parallel Flat ce87 Pbcn 8 27.2160 6.9748 7.4090 90 90 90 1.3237-105.26 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates dc50 C2/c 4 10.9412 7.0318 21.2659 90 59.301 90 1.3233-105.26 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ai88 P21/c 4 9.1902 5.1003 16.1348 90 67.305 90 1.3341-105.16 CrissCross Asymmetric Ribbon ak76 P21/c 4 6.5396 6.7809 16.4986 90 66.675 90 1.3855-105.16 Sheets Zigzag Ribbon No dimers Parallel Flat ai36 P21/c 4 8.9571 7.0105 11.3381 90 88.815 90 1.3077-105.14 Sheets Symmetric Ribbon Polar Parallel Stepped fa74 P21/c 4 4.0187 27.5231 6.4127 90 101.131 90 1.3375-105.13 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca79 P-1 2 9.6790 7.7299 7.8646 61.235 67.854 111.949 1.3351-105.08 Sheets Asymmetric Ribbon Flat db36 C2 2 7.3648 7.0014 13.6844 90 96.984 90 1.3290-105.04 Sheets Symmetric Ribbon Polar Parallel Stepped fa102 P21/c 4 4.0531 27.9402 6.9108 90 63.557 90 1.3284-104.93 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca111 P-1 2 4.9545 7.6817 9.9880 66.903 80.687 82.713 1.3521-104.86 Sheets Asymmetric Ribbon Flat ak37 P21/c 4 8.9584 6.8458 11.6266 90 90.602 90 1.3055-104.86 Sheets Symmetric Ribbon Polar Parallel Stepped af19 P21 2 7.5519 7.0127 6.8473 90 108.088 90 1.3502-104.86 Sheets Symmetric Ribbon Polar Parallel Flat au61 Pna21 4 28.2400 5.6888 4.1857 90 90 90 1.3843-104.73 CrissCross Symmetric Ribbon Polar am101 P21/n 4 4.0808 10.3623 16.3821 90 95.865 90 1.3507-104.69 Sheets Asymmetric Ribbon Stepped ad109 Pc 2 4.0870 14.4304 6.9567 90 56.985 90 1.3528-104.26 Sheets Symmetric Ribbon Polar Parallel Undulates Table S2.4 The low energy structures found for 5-vinyluracil with the CH2 group over the carbonyl at C4. Label S.G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analyisis ai72 P21/c 4 6.1255 6.9632 16.1720 90 67.705 90 1.4375-109.33 Sheets Symmetric Ribbon Polar Parallel Flat ak91 P21/c 4 9.7688 7.0107 10.1476 90 111.182 90 1.4158-109.23 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ak83 P21/c 4 9.1892 7.0237 10.1694 90 99.786 90 1.4184-109.00 Sheets Symmetric Ribbon Polar Parallel Stepped ca105 P-1 2 4.9470 6.9941 9.9112 89.564 109.271 82.794 1.4303-108.75 Sheets Symmetric Ribbon Non-polar Parallel Stepped ca95 P-1 2 6.6319 3.9048 13.0561 83.494 80.595 104.827 1.4418-108.69 Sheets Symmetric Ribbon Non-polar Parallel Flat de49 C2/c 4 13.6682 14.8877 17.8680 90 159.383 90 1.4332-108.62 Sheets Symmetric Ribbon Polar Parallel Flat ca103 P-1 2 4.0356 5.4789 15.4779 107.912 99.785 92.608 1.4373-108.02 Sheets Symmetric Ribbon Non-polar Parallel Stepped fc36 P21/n 4 4.5443 7.0133 20.4006 90 86.505 90 1.4137-108.00 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de30 C2/c 4 12.8917 3.9477 26.2123 90 106.447 90 1.4342-108.00 CrissCross Symmetric Ribbon Non-polar ak2 P21/c 4 13.4347 3.7410 12.8766 90 105.822 90 1.4734-107.98 Sheets 6,3-Net Free O2 Undulates af78 P21 2 4.6270 7.0153 10.1332 90 99.410 90 1.4136-107.96 Sheets Symmetric Ribbon Polar Parallel Stepped fa9 P21/c 4 3.9058 25.8254 6.7812 90 70.197 90 1.4255-107.94 Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates 17

fa61 P21/c 4 4.5162 27.4197 6.9906 90 131.717 90 1.4198-107.92 Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates fc86 P21/c 4 4.5448 7.0127 20.6389 90 99.205 90 1.4129-107.89 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped af74 P21 2 4.6269 7.0148 10.1390 90 80.596 90 1.4129-107.85 Sheets Symmetric Ribbon Polar Parallel Stepped ay115 P1 4 14.7232 7.0987 6.9795 61.634 90.007 90.014 1.4293-107.83 Sheets Symmetric Ribbon Polar Parallel Stepped fc100 P21/n 4 4.5469 5.2598 27.2113 90 85.138 90 1.4148-107.78 CrissCross Symmetric Ribbon Non-polar fc54 P21/n 4 4.4652 7.0114 20.7333 90 93.593 90 1.4162-107.73 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ab34 P-1 2 6.9727 11.0908 8.6447 41.878 132.761 128.517 1.4419-107.71 Sheets Symmetric Ribbon Non-polar Parallel Flat cc107 Pca21 8 7.0136 10.0301 18.7299 90 90 90 1.3926-107.70 Sheets Symmetric Ribbon Polar Parallel Undulates fc99 P21/n 4 3.7627 5.8010 29.5797 90 82.614 90 1.4328-107.70 CrissCross Symmetric Ribbon Non-polar fc80 P21/n 4 5.2266 4.5701 27.1463 90 89.967 90 1.4149-107.60 CrissCross Symmetric Ribbon Non-polar fc29 P21/n 4 8.6640 6.9590 10.6805 90 98.876 90 1.4420-107.53 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped am88 P21/n 4 6.9503 6.1585 17.0389 90 117.793 90 1.4220-107.53 Sheets Symmetric Ribbon Non-polar Parallel Flat fc12 P21/n 4 5.8824 3.7538 28.9331 90 90.113 90 1.4360-107.35 CrissCross Symmetric Ribbon Non-polar cc28 Pbca 8 6.9289 6.9625 26.9079 90 90 90 1.4135-107.30 Sheets Symmetric Ribbon Polar Parallel Undulates ce81 P21 8 12.4180 14.8032 7.0041 89.265 90 90 1.4252-107.29 Sheets Symmetric Ribbon Polar Parallel Flat fa64 P21/c 4 7.0354 18.8564 7.9934 90 141.390 90 1.3864-107.23 Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates ak9 P21/c 4 13.3644 3.7315 12.9399 90 76.603 90 1.4615-107.19 Sheets 6,3-Net Free O2 Undulates aj64 P-1 4 6.9574 15.0328 6.9210 90.004 89.969 116.074 1.4110-107.13 Sheets Symmetric Ribbon Polar Parallel Flat fc9 P21/n 4 7.0134 4.4208 21.4895 90 78.863 90 1.4034-106.83 Sheets Symmetric Ribbon Non-polar Parallel Undulates bg79 Pc 4 29.4530 7.0136 3.8006 124.847 90 90 1.4239-106.78 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped da20 Cc 2 6.8774 14.7546 7.5768 90 122.159 90 1.4095-106.78 Sheets Symmetric Ribbon Polar Parallel Flat cd14 Pbcn 8 27.2826 6.9651 6.8295 90 90 90 1.4139-106.77 Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates az23 P212121 4 20.5655 4.5422 7.0196 90 90 90 1.3991-106.74 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates ca90 P-1 2 6.2110 6.9844 8.5192 90.945 95.677 118.933 1.4292-106.74 Sheets Symmetric Ribbon Non-polar Parallel Stepped dc13 C2/c 4 12.8058 3.9107 26.7908 90 75.139 90 1.4149-106.71 Sheets Symmetric Ribbon Non-polar Anti-Parallel Flat de77 C2/c 4 28.0142 6.9537 6.8135 90 101.364 90 1.4101-106.71 CrissCross Symmetric Ribbon Non-polar ak56 P21/c 4 8.4071 6.9787 11.0597 90 83.318 90 1.4236-106.69 Sheets Symmetric Ribbon Polar Parallel Stepped aq42 P212121 4 7.0197 20.5626 4.5440 90 90 90 1.3988-106.64 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates au29 Pna21 4 29.3393 3.7311 5.9024 90 90 90 1.4199-106.56 CrissCross Symmetric Ribbon Polar ai80 P21/c 4 7.3324 6.5861 12.9409 90 80.492 90 1.4885-106.45 Sheets 6,3-Net Free O2 Undulates dc91 C2/c 4 12.4755 6.1231 20.8383 90 55.447 90 1.3996-106.38 CrissCross Symmetric Ribbon Non-polar ar76 Pc 4 5.9149 29.2710 3.7284 90 90 90 1.4213-106.30 CrissCross Symmetric Ribbon Polar dd52 C2/c 4 6.7544 6.9340 27.9704 90 93.770 90 1.4037-106.16 Sheets Symmetric Ribbon Non-polar Anti-Parallel Flat ad41 Pc 2 3.8052 14.8741 7.0145 90 125.234 90 1.4146-106.10 Sheets Symmetric Ribbon Polar Parallel Flat 18

de103 C2/c 4 24.3538 4.0308 24.6135 90 148.470 90 1.4522-105.73 Sheets Symmetric Ribbon Non-polar Parallel Stepped dc22 C2/c 4 10.1273 6.9612 18.4475 90 81.401 90 1.4269-105.72 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped dc66 C2/c 4 10.1331 6.9594 18.4415 90 98.601 90 1.4270-105.61 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de52 C2/c 4 12.9200 14.8091 7.0303 90 90.698 90 1.3642-105.61 Sheets Symmetric Ribbon Polar Parallel Flat ak60 P21/c 4 10.4083 7.0025 9.4226 90 107.353 90 1.3996-105.55 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de61 C2/c 4 20.8494 7.0184 16.5272 90 32.722 90 1.4036-105.51 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped cc50 Pbca 8 7.0104 6.2955 29.5907 90 90 90 1.4050-105.51 Sheets Symmetric Ribbon Polar Parallel Undulates dd35 C2/c 4 6.9391 6.9993 27.3926 90 102.297 90 1.4116-105.48 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped au53 Pna21 4 21.0320 4.4952 7.0296 90 90 90 1.3804-105.37 Sheets Symmetric Ribbon Polar Parallel Undulates db68 C2 2 6.9662 6.9902 13.4400 90 91.633 90 1.4024-105.30 Sheets Symmetric Ribbon Polar Parallel Stepped de42 C2/c 4 22.6338 6.9630 18.9134 90 25.592 90 1.4251-105.25 Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped am25 P21/c 4 6.9516 14.9046 7.6335 90 125.270 90 1.4208-105.20 Sheets Symmetric Ribbon Non-polar Parallel Flat dd34 C2/c 4 10.1394 7.0003 18.4502 90 98.184 90 1.4156-105.12 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped az38 P212121 4 28.2273 5.0591 4.4468 90 90 90 1.4447-105.07 Sheets 4,4-Grid IURACL10 fa102 P21/c 4 3.6799 27.0174 6.7360 90 71.403 90 1.4454-105.05 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates dd90 C2/c 4 13.0409 5.0286 21.1877 90 77.119 90 1.3547-105.03 CrissCross Symmetric Ribbon Non-polar db31 C2 2 9.4843 6.9914 9.9109 90 81.061 90 1.4132-104.91 Sheets Symmetric Ribbon Polar Parallel Stepped ce24 P21 8 26.3058 6.9577 7.7170 69.578 90 90 1.3862-104.77 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates af100 P21 2 4.8468 4.6585 15.2692 90 67.907 90 1.4360-104.71 Sheets 4,4-Grid IURACL10 inverted cd74 P21 8 26.0139 6.9627 7.3696 95.239 90 90 1.3804-104.65 Sheets Symmetric Ribbon Polar Parallel Undulates ak90 P21/c 4 9.3717 7.0252 10.3292 90 101.930 90 1.3788-104.63 Sheets Symmetric Ribbon Non-polar Parallel Stepped af111 P21 2 3.8232 5.6320 14.7857 90 79.915 90 1.4635-104.62 Sheets 4,4-Grid IURACL10 inverted cc95 Pca21 8 7.0134 10.1700 18.8515 90 90 90 1.3646-104.48 Sheets Symmetric Ribbon Non-polar Parallel Undulates fc50 P21/c 4 5.1546 4.3379 28.6164 90 93.136 90 1.4360-104.47 Sheets 4,4-Grid IURACL10 am143 P21/c 4 3.8042 5.6558 29.3122 90 94.257 90 1.4587-104.46 Sheets 4,4-Grid IURACL10 ab65 P-1 2 6.1975 6.9896 10.2130 89.733 88.171 48.698 1.3812-104.43 Sheets Symmetric Ribbon Non-polar Parallel Stepped Table S2.5 The low energy structures found for 5-vinyluracil with the CH2 group over the hydrogen at C6 Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analyisis ab20 P-1 2 6.9833 3.7609 14.2817 96.379 86.945 58.111 1.4622-109.11 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab61 P-1 2 9.4794 4.8150 7.2609 105.748 97.441 78.729 1.4712-108.84 Sheets Asymmetric Ribbon Flat fc16 P21/n 4 5.9120 3.7447 28.5370 90 95.651 90 1.4593-108.75 CrissCross Symmetric Ribbon Non-Polar cd73 Pbcn 8 27.3078 7.0085 6.6393 90 90 90 1.4440-108.71 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates 19

fa19 P21 4 3.7256 28.2724 5.9727 90 89.406 90 1.4584-108.60 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped bj52 Pn 4 28.6027 5.9380 3.7327 90 97.499 90 1.4596-108.51 CrissCross Symmetric Ribbon Polar cc125 Pbca 8 7.0198 6.7584 26.8716 90 90 90 1.4393-108.40 Sheets Symmetric Ribbon Polar Parallel Undulates am103 P21/c 4 7.0031 13.5470 12.8108 90 30.887 90 1.4705-108.29 Sheets Symmetric Ribbon Non-Polar Parallel Stepped fc18 P21/n 4 3.7323 5.8810 29.2935 90 99.967 90 1.4487-108.19 CrissCross Symmetric Ribbon Non-Polar fa21 P21 4 3.7302 28.7804 5.9081 90 90.186 90 1.4465-108.06 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates da20 Cc 2 7.6084 13.8048 7.3608 90 123.969 90 1.4309-107.90 Sheets Symmetric Ribbon Polar Parallel Undulates dd11 C2/c 4 14.0523 6.6502 13.6810 90 96.124 90 1.4434-107.71 Sheets Symmetric Ribbon Non-Polar Parallel Undulates be51 Pc 4 28.8474 3.7187 5.9197 90 90 90 1.4447-107.61 CrissCross Symmetric Ribbon Polar ca95 P-1 2 7.0112 7.9904 6.6813 61.729 101.772 89.034 1.4339-107.50 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ad69 Pc 2 3.7343 14.4224 6.9880 90 57.551 90 1.4444-107.48 Sheets Symmetric Ribbon Polar Parallel Flat ai112 P21/c 4 13.9525 7.0053 6.7356 90 102.661 90 1.4283-107.21 Sheets Symmetric Ribbon Polar Parallel Stepped am124 P21 4 7.0334 6.6301 13.7708 90 83.928 90 1.4367-106.98 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ca39 P-1 2 7.0590 5.8957 10.8651 98.953 76.311 133.279 1.4343-106.68 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ca27 P-1 2 8.5545 7.0748 7.7425 116.764 112.991 105.837 1.4216-106.49 Sheets Symmetric Ribbon Non-Polar Parallel Flat ca106 P-1 2 7.0454 5.6670 8.9826 84.684 99.251 113.908 1.4182-106.45 Sheets Symmetric Ribbon Non-Polar Parallel Flat ai97 P21/c 4 10.8898 7.0579 8.3947 90 94.101 90 1.4256-106.41 Sheets Symmetric Ribbon Polar Parallel Stepped ak87 P21/c 4 9.3679 6.9209 22.6470 90 153.829 90 1.4167-106.29 Sheets Symmetric Ribbon Polar Parallel Flat dd18 C2/c 4 8.0514 7.0142 22.5927 90 89.028 90 1.4383-105.99 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc92 P21/c 4 6.4763 7.0384 14.2468 90 99.726 90 1.4333-105.99 Sheets Symmetric Ribbon Polar Anti-Parallel Flat cc33 Pbca 8 7.0305 6.4003 28.5729 90 90 90 1.4272-105.55 Sheets Symmetric Ribbon Polar Parallel Undulates cc127 Pbca 8 7.0302 6.4003 28.5740 90 90 90 1.4272-105.52 Sheets Symmetric Ribbon Polar Parallel Undulates cc64 Pbca 8 7.0303 6.4003 28.5750 90 90 90 1.4271-105.50 Sheets Symmetric Ribbon Polar Parallel Undulates am74 P21/n 4 3.7622 9.7524 17.5792 90 83.053 90 1.4329-105.34 CrissCross Asymmetric Ribbon al20 P2/c 4 14.3600 6.9137 6.4735 90 86.590 90 1.4300-105.30 Sheets Symmetric Ribbon Non-Polar Parallel Stepped av25 P21 4 6.7585 14.1266 6.9922 90 90 104.040 1.4166-105.11 Sheets Symmetric Ribbon Polar Parallel Stepped ai33 P21/c 4 11.6610 4.3818 17.5388 90 135.470 90 1.4598-104.99 Sheets 6,3-Net; Herringbone JESMAW Undulates de45 C2/c 4 21.7348 6.8846 10.4204 90 56.288 90 1.4147-104.85 Sheets Symmetric Ribbon Polar Anti-Parallel Flat dd22 P-1 4 18.2165 4.8431 26.8415 71.554 138.880 87.071 1.4021-104.83 Sheets Asymmetric Ribbon Stepped dc80 P-1 4 18.2166 4.8426 17.7644 122.030 96.475 92.929 1.4022-104.81 Sheets Asymmetric Ribbon Stepped dc77 C2/c 4 12.7613 5.6390 23.3910 90 127.846 90 1.3804-104.68 CrissCross Symmetric Ribbon Non-Polar am111 P21/c 4 4.0141 9.5469 17.2963 90 93.419 90 1.3866-104.67 CrissCross Asymmetric Ribbon dc75 Cc 4 12.8031 3.8039 26.9552 90 89.542 90 1.3978-104.50 CrissCross Symmetric Ribbon Non-Polar ce49 Pca21 8 27.7788 7.0257 6.6275 90 90 90 1.4186-104.44 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates 20

ak56 P21/c 4 11.3094 6.9450 8.1876 90 90.772 90 1.4268-104.38 Sheets Symmetric Ribbon Non-Polar Parallel Flat Table S2.6 The low energy structures found for 5-cyanouracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analyisis 5-Cyano P21/c 4 9.0098 6.6035 9.1805 90 98.124 90 Sheets Ladder Flat Anti-Parallel au93 Anti-Parallel Pc 4 13.514 9.1035 5.8526 127.74 90 90 1.5993-116.85 Dimers N3 O1 dimers NH N(C) 6,3-Net am109 P21/n 4 5.6726 7.8269 12.318 90 87.821 90 1.6663-115.9 Dimers N3 O2 dimers NH N(C) 3-D cb140 Pbca 8 13.394 13.953 6.1863 90 90 90 1.5752-115.14 Chains 4,4-Grid NH N(C) ak31 P21/c 4 9.3195 6.7354 12.049 90 129.99 90 1.5714-115.09 Sheets Ladder Flat am34 P21/n 4 5.679 11.196 9.3117 90 103.52 90 1.5818-114.9 Dimers N3 O1 dimers NH N(C) 6,3-Net aj67 P-1 4 10.544 6.689 14.008 90 41.927 71.506 1.5673-114.78 Chains 4,4-Grid NH N(C) am64 P21/n 4 5.8656 13.226 9.0637 90 53.093 90 1.6196-114.75 Dimers N1 O1 dimers NH N(C) 6,3-Net am44 P21/n 4 5.9347 9.3527 13.013 90 125.87 90 1.5559-114.48 Sheets Asymmetric Ribbon Undulates as26 Pna21 4 14.122 6.6821 6.2061 90 90 90 1.5549-114.48 Chains 4,4-Grid NH N(C) aj18 Pc 4 7.9796 6.145 13.596 90 57.79 90 1.6144-114.48 Dimers N1 O1 dimers NH N(C) 6,3-Net cb66 P21 8 13.466 11.365 13.366 90 90 33.53 1.6119-114.23 Dimers N1 O1 dimers NH N(C) 6,3-Net ay74 Pc 4 12.629 3.7562 11.991 90 90 90 1.6009-114.18 None NH N(C) only 3-D av73 Pna21 4 11.677 12.546 3.809 90 90 90 1.6318-113.94 Chains 3-D NH N(C) cd125 Pna21 8 12.497 6.6911 14.009 90 90 90 1.5547-113.75 Chains 4,4-Grid NH N(C) am55 P21/c 4 3.7367 12.541 12.061 90 88.954 90 1.6114-113.74 Dimers N1 O1 dimers NH N(C) 6,3-Net cd69 Pc 8 14.179 6.6887 14.11 90 90 118.15 1.5435-113.59 Chains 4,4-Grid NH N(C) ag26 Pc 2 6.1697 6.753 7.1381 90 89.287 90 1.5311-113.57 Chains 4,4-Grid NH N(C) av52 Pna21 4 7.6742 13.057 5.5611 90 90 90 1.6342-113.5 Chains 3-D NH N(C) am22 P21/n 4 3.8344 11.725 12.449 90 90.667 90 1.6272-113.4 Dimers N3 O1 dimers NH N(C) 6,3-Net as44 Pna21 4 11.873 12.611 3.8516 90 90 90 1.5791-113.22 Chains 3-D NH N(C) bd2 P1 4 11.801 13.44 3.8705 108.93 96.457 77.983 1.6053-112.99 Dimers N1 O1 dimers NH N(C) 6,3-Net am68 P21/c 4 6.8211 14.19 9.2455 90 137.55 90 1.5076-112.87 Chains 4,4-Grid NH N(C) cc82 P21/b 8 6.7465 14.175 23.178 147.17 90 90 1.5155-112.79 Chains 4,4-Grid NH N(C) ab24 P-1 2 7.3847 6.1933 7.6866 92.205 104.36 122.05 1.6123-112.61 Sheets Ladder Stepped Parallel da1 Cc 2 8.062 6.6968 14.112 90 128.62 90 1.5297-112.6 Chains 4,4-Grid NH N(C) ax3 Pn 4 5.2104 12.616 8.511 94.539 90 90 1.6327-112.5 Chains 4,4-Grid NH N(C) ai96 P21/c 4 9.2698 6.6822 14.055 90 42.826 90 1.5387-112.49 Chains 4,4-Grid NH N(C) ay45 Pca21 4 11.87 6.0797 7.6838 90 90 90 1.6422-112.44 None NH N(C) only 3-D 21

am27 P21/c 4 5.547 13.177 7.6882 90 90.3 90 1.6205-112.39 Dimers N1 O1 dimers NH N(C) 6,3-Net ca78 P-1 2 5.8107 8.6745 11.499 37.371 121.03 126.64 1.6187-112.34 Sheets Symmetric Ribbon Non-Polar Parallel Stepped al97 P2/c 4 7.7851 6.713 14.085 90 125.64 90 1.5222-112.22 Chains 4,4-Grid NH N(C) am66 P21/c 4 3.7152 13.452 11.482 90 90.844 90 1.5871-112.16 Dimers N3 O1 dimers NH N(C) 6,3-Net am43 P21/c 4 6.7756 14.267 6.687 90 111.09 90 1.5099-112.07 Chains 4,4-Grid NH N(C) am57 P21/n 4 3.7134 12.24 12.982 90 76.651 90 1.5861-112.02 Dimers N3 O1 dimers NH N(C) 6,3-Net ao10 P-1 4 6.6957 7.3551 14.952 118.67 109.06 63.411 1.5925-111.97 Sheets Ladder Stepped Parallel am54 P21/n 4 3.6429 13.117 12.064 90 75.162 90 1.6342-111.91 Dimers N1 O1 dimers NH N(C) 6,3-Net (a) (b) Figure S2.4 The ladders can adopt either (a) a parallel arrangement as seen for ab24 or (b) an anti-parallel arrangement as observed in the experimentally observed structure (C - dark grey; H - light grey; N - blue; O - red). 22

Figure S2.6 red). The 4,4-grid formed by N-H N C interactions and N1-H O2 hydrogen bonds (cb140) (C - dark grey; H - light grey; N - blue; O - 23 (a) (b) Figure S2.5 The 6,3-nets formed by N-H N C interactions and (a) N3 O1 dimers (au93) and (b) N1 O1 dimers (cb66) (C - dark grey; H - light grey; N - blue; O - red).

Table S2.7 The low energy structures found for 5-hydroxyuracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis QARWAI P-1 2 4.6195 7.0493 7.3452 88.169 81.504 86.245 Sheets Symmetric Ribbon Non-Polar Parallel Flat am88 P21/n 4 3.5632 10.5313 13.8034 90 112.353 90 1.7760-114.79 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers av76 P1 4 9.9605 14.4060 3.4875 104.010 79.695 92.482 1.7809-113.06 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers av38 Pna21 4 13.7907 10.2217 3.3823 90 90 90 1.7844-112.59 Dimers N3 O1 dimers NH OH 3-D cd47 P21/n 8 15.1233 6.4028 10.7721 90 90 109.277 1.7282-112.37 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers ca15 P-1 2 6.2012 7.2544 6.4631 68.404 117.616 99.242 1.7760-112.09 Sheets Symmetric Ribbon Non-Polar Parallel Flat am39 P21/c 4 5.7261 10.8625 8.0981 90 81.059 90 1.7098-111.77 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers cb57 P21 8 6.1483 10.7922 15.2426 90 90 90 1.6823-111.38 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers cd51 Pbcn 8 15.1044 10.8486 6.2003 90 90 90 1.6747-110.85 Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers Figure S2.7 The 4,4-grid formed by dimers of 5-hydroxyuracil (am88) (C - dark grey; H - light grey; N - blue; O - red). Table S2.8 The low energy structures found for 5-aminouracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis am91 P21/n 4 4.3222 8.9167 13.3593 90 98.739 90 1.6589-128.16 Dimers N3 O2 dimers N1 NH2 3-D NH2 O1 am131 P21/n 4 5.2466 8.8402 11.0411 90 77.093 90 1.6913-125.63 Dimers N1 O1 dimers N3 NH2 3-D NH2 O2 dimers am57 P21/c 4 3.7977 12.4474 11.8951 90 116.434 90 1.6767-125.51 Dimers N3 O1 dimers N1 NH2 3-D NH2 O2 dimers fc35 P21/n 4 5.7970 3.8284 23.8364 90 74.765 90 1.6540-125.14 CrissCross Symmetric Ribbon Non-Polar bd74 Pna21 4 23.2749 5.8196 3.8165 90 90 90 1.6331-123.87 CrissCross Symmetric Ribbon Polar 24

Table S2.9 The low energy structures found for 5-nitrouracil, using the gas phase ab initio optimized conformation Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis NIMFOE P21/n 4 5.873 9.693 10.4561 90 104.07 90 Sheets Asymmetric Ribbon? NIMFOE 01 Pbca 8 8.308 10.426 13.363 90 90 90 Sheets Asymmetric Ribbon Stepped NIMFOE 02 P212121 4 5.4342 9.8406 10.3659 90 90 90 Sheets 4,4-Grid No dimers NIMFOE02 am112 P21/n 4 5.0039 10.9036 10.5772 90 76.227 90 1.8615-118.54 Dimers N1 O1 dimers NH ON 6,3-Net fa74 P21/c 4 4.9944 19.4935 6.4364 90 109.193 90 1.7630-117.34 Sheets Ladder Undulates Anti-Parallel ab33 P-1 2 6.4856 4.9982 11.4104 112.971 60.180 109.790 1.7953-116.83 Sheets Ladder Flat Parallel de9 C2/c 4 12.3772 4.9215 19.5896 90 83.332 90 1.7607-116.28 CrissCross Ladder am124 P21/n 4 4.8874 10.9074 11.0213 90 103.941 90 1.8298-114.86 Dimers N3 O1 dimers NH ON 6,3-Net aq62 P212121 4 6.3642 8.9562 10.5543 90 90 90 1.7344-114.82 Sheets 4,4-Grid No dimers NIMFOE02 am101 P21/c 4 7.6992 6.7482 11.3318 90 93.195 90 1.7750-114.58 Sheets Asymmetric Ribbon Stepped db56 C2 2 12.4392 4.7750 11.4140 90 118.740 90 1.7552-113.96 Sheets 4,4-Grid No dimers NH ON No free D or A ca100 P-1 2 6.4544 4.9394 15.7500 105.788 140.215 70.651 1.7215-113.90 Sheets Ladder Stepped Parallel dd65 C2/c 4 12.4331 4.8504 19.6041 90 80.927 90 1.7875-113.89 Sheets 4,4-Grid No dimers NH ON No free D or A aw43 P1 4 7.9469 12.5201 5.7150 90 90 90 1.8349-113.80 3-D ai56 P21/c 4 9.9228 5.4124 11.3762 90 70.199 90 1.8150-113.74 Sheets 6,3-Net; Herringbone JESMAW Undulates al56 Pc 4 10.2791 6.6983 10.3544 90 125.588 90 1.7996-113.74 Sheets Ladder Flat Anti-Parallel ab95 P-1 2 8.3828 6.3807 6.9190 121.315 114.270 76.984 1.8102-113.24 Sheets Asymmetric Ribbon Flat ak15 P21/c 4 6.6466 12.1573 7.3352 90 104.725 90 1.8201-112.95 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ca45 P-1 2 6.2375 6.3332 8.5342 94.100 104.657 113.046 1.7711-112.81 Sheets Asymmetric Ribbon Flat fa97 P21/c 4 6.6756 16.7854 6.4701 90 59.447 90 1.6712-112.69 Sheets Ladder Undulates Anti-Parallel de27 C2/c 4 28.1883 4.9230 12.9731 90 43.912 90 1.6713-112.11 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab16 P-1 2 7.0233 6.7165 8.9669 91.350 132.410 82.941 1.6888-111.58 Sheets Symmetric Ribbon Non-Polar Parallel Flat fa96 P21/c 4 6.5551 15.1523 6.8224 90 118.515 90 1.7523-111.27 Sheets Ladder Undulates Anti-Parallel ai47 P21/c 4 14.2689 6.6617 8.4559 90 47.649 90 1.7565-111.00 Sheets Ladder Flat Parallel dc79 C2/c 4 12.0250 5.4953 18.5391 90 96.560 90 1.7146-110.98 CrissCross Ladder aq22 P212121 4 14.0768 6.2626 6.8040 90 90 90 1.7395-110.97 Chains 4,4-Grid NH ON dd42 C2/c 4 7.1306 10.7334 16.4895 90 106.174 90 1.7216-110.94 Sheets Asymmetric Ribbon Flat ak52 P21/c 4 11.8299 6.5896 8.4498 90 61.959 90 1.7947-110.86 Sheets Ladder Flat Anti-Parallel au44 Pna21 4 14.0682 6.8009 6.2877 90 90 90 1.7344-110.85 Chains 4,4-Grid NH ON 25

ak42 P21/c 4 Undulates Anti-Parallel 7.8830 6.7505 11.1072 90 92.122 90 1.7665-110.79 Sheets Zigzag Ribbon No dimers Parallel Flat am19 P21/n 4 5.2680 10.1670 10.8102 90 94.081 90 1.8067-110.62 Dimers N3 O2 dimers NH ON 3-D am80 P21/n 4 6.1137 8.4076 11.4171 90 95.895 90 1.7874-110.58 Dimers N3 O1 dimers NH ON 6,3-Net * DHA = 119 ai94 P21/c 4 7.3358 6.5391 12.6773 90 94.874 90 1.7220-110.51 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc21 P21/c 4 4.9660 4.8384 26.0654 90 110.852 90 1.7827-110.40 CrissCross Ladder cc76 Pca21 8 6.6956 9.7655 18.6095 90 90 90 1.7150-110.39 Sheets Ladder Undulates Parallel fa15 P21/c 4 6.7940 14.5622 7.9122 90 128.339 90 1.6993-110.36 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates cd1 Pbcn 8 8.0808 13.1430 11.1029 90 90 90 1.7696-110.29 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab39 P-1 2 6.7469 3.8548 18.0101 114.127 44.790 110.447 1.7396-110.26 Sheets Ladder Flat Parallel av25 Pna21 4 10.7566 10.1433 5.5253 90 90 90 1.7308-110.25 Sheets 4,4-Grid No dimers NIMFOE02 cb107 Pbca 8 6.5375 10.7051 17.6862 90 90 90 1.6859-110.24 Sheets Asymmetric Ribbon Stepped ab40 P-1 2 6.8557 4.7194 16.7032 53.129 44.642 62.322 1.7211-110.12 Sheets Ladder Flat Parallel cc100 Pca21 8 6.7067 11.9391 15.7464 90 90 90 1.6550-110.05 Sheets Ladder de104 C2/c 4 11.5574 6.5472 19.7628 90 122.891 90 1.6618-110.00 CrissCross Ladder cd39 Pbcn 8 17.9490 6.4693 10.6725 90 90 90 1.6839-109.93 Sheets Asymmetric Ribbon Flat am55 P21/c 4 7.7279 11.3269 6.9360 90 74.489 90 1.7835-109.91 Sheets Asymmetric Ribbon Stepped cb90 Pbca 8 14.5868 8.3407 10.7014 90 90 90 1.6028-109.61 Sheets Asymmetric Ribbon Undulates am22 P21/n 4 6.5420 10.4231 8.6869 90 91.420 90 1.7620-109.57 Sheets Ladder Undulates Parallel de54 C2/c 4 36.4460 3.6296 28.7182 90 161.664 90 1.7461-109.47 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de43 C2/c 4 11.4419 6.7743 16.8656 90 69.257 90 1.7069-109.45 CrissCross Ladder am27 P21/c 4 5.0714 9.3646 12.5301 90 94.716 90 1.7593-109.28 CrissCross Asymmetric Ribbon ba38 P21 4 16.1160 6.7829 5.4708 90 90 90 1.7447-109.27 Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates fa58 P21 4 6.7342 25.0468 3.6517 90 72.899 90 1.7723-109.26 Sheets 4,4-Grid No dimers NH ON No free D or A dc89 C2/c 4 11.8567 6.6768 19.2302 90 52.529 90 1.7271-109.21 Sheets Zigzag Ribbon No dimers Anti-Parallel Stepped de97 C2/c 4 11.5300 6.9999 16.4615 90 109.258 90 1.6638-109.20 CrissCross Ladder af66 P21 2 5.0289 4.9311 11.6537 90 84.322 90 1.8141-109.13 Sheets 6,3-Net IURACL10 af40 P21 2 4.9166 4.8307 12.9860 90 110.107 90 1.8012-109.08 Sheets 6,3-Net IURACL10 cc70 Pbca 8 5.6941 11.4443 19.1340 90 90 90 1.6736-109.03 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ai53 P21/c 4 8.5180 6.3504 11.6884 90 78.934 90 1.6815-109.03 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am67 P21/c 4 6.8458 12.4147 7.3078 90 68.755 90 1.8024-109.00 Chains 4,4-Grid NH ON am65 P21/n 4 5.2238 10.9270 11.2690 90 75.806 90 1.6731-108.99 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd43 Pna21 8 25.5229 3.6220 12.9027 90 90 90 1.7495-108.98 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd8 P21 8 13.6247 13.4977 6.6617 90 90 91.756 1.7041-108.95 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab120 P-1 2 9.0724 7.0079 6.5524 83.440 90.699 132.337 1.7119-108.89 Sheets Symmetric Ribbon Non-Polar Parallel Flat 26

ak62 P21/c 4 10.3907 5.5268 11.3052 90 107.826 90 1.6882-108.79 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc59 P21/n 4 7.0142 6.6952 12.9133 90 103.446 90 1.7690-108.79 Sheets Ladder Flat Anti-Parallel am105 P21/c 4 6.2548 10.5274 10.3047 90 66.452 90 1.6774-108.73 Sheets Asymmetric Ribbon Flat de98 C2/c 4 32.0853 6.4905 26.6475 90 167.410 90 1.7252-108.68 Dimers N3 O1 dimers NH ON 6,3-Net ai46 P21/c 4 11.2744 6.7847 7.7511 90 87.481 90 1.7615-108.68 Sheets Zigzag Ribbon No dimers Parallel Stepped ai30 P21/c 4 12.5058 6.7547 7.2641 90 103.083 90 1.7457-108.65 Sheets Zigzag Ribbon No dimers Anti-Parallel Stepped da51 Cc 2 12.0910 6.7634 13.3855 90 147.294 90 1.7641-108.63 Chains 4,4-Grid NH ON * DHA = 128 cb79 Pbca 8 12.5770 13.9197 6.8195 90 90 90 1.7479-108.58 Dimers N3 O1 dimers NH ON 6,3-Net Figure S2.8 The 6,3-net formed by dimers of 5-nitrouracil (am112) (C - dark grey; H - light grey; N - blue; O - red). Table S2.10 The low energy structures found for 5-nitrouracil, using the constrained planar conformation for NO2 Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis NIMFOE P21/n 4 5.873 9.693 10.4561 90 104.07 90 Sheets Asymmetric Ribbon? NIMFOE 01 Pbca 8 8.308 10.426 13.363 90 90 90 Sheets Asymmetric Ribbon Stepped NIMFOE 02 P212121 4 5.4342 9.8406 10.3659 90 90 90 Sheets 4,4-Grid No dimers NIMFOE02 aq24 P212121 4 10.725 9.7888 5.61 90 90 90 1.7715-118.23 Sheets 4,4-Grid No dimers NIMFOE02 cb93 P21/c 8 9.4677 11.996 10.206 90 82.825 90 1.8144-115.55 Sheets 6,3-Net No dimers NH ON No free D or A ca85 P-1 2 6.8016 5.1659 11.425 81.785 117.63 123.13 1.7714-114.65 Sheets Ladder Flat Parallel fc77 P21/n 4 10.876 6.7721 9.7061 90 55.302 90 1.7752-113.22 Sheets Ladder Flat Anti-Parallel 27

bb70 P21 4 14.414 6.747 6.089 90 90 90 1.762-113.02 Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates dc62 C2/c 4 8.2093 6.7989 21.368 90 96.946 90 1.7626-113.01 Sheets Ladder Flat Anti-Parallel fa64 P21 4 5.0498 20.671 6.031 90 74.948 90 1.7163-112.92 Sheets Ladder Undulates Anti-Parallel az91 P212121 4 14.402 6.7469 6.0979 90 90 90 1.7609-112.9 Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates fa10 P21 4 5.0622 20.709 6.0028 90 104.86 90 1.7154-112.82 Sheets Ladder Undulates Anti-Parallel am51 P21/n 4 5.4176 10.325 10.646 90 75.311 90 1.8113-112.47 Dimers N3 O1 dimers NH ON 6,3-Net dc1 C2/c 4 12.525 4.95 21.027 90 64.542 90 1.7728-112.37 Sheets 4,4-Grid No dimers NH ON No free D or A am14 P21/c 4 5.3658 11.069 10.241 90 100.45 90 1.7443-112.24 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ai54 P21/c 4 6.1626 6.8156 14.179 90 89.918 90 1.752-111.9 Chains 4,4-Grid NH ON dd59 C2/c 4 12.539 4.9565 21.708 90 65.121 90 1.705-111.64 CrissCross Ladder ai90 P21/c 4 12.14 5.2903 11.782 90 127.69 90 1.7425-111.59 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd26 C2/c 4 12.541 4.955 29.286 90 42.296 90 1.7039-111.54 CrissCross Ladder ak97 P21/c 4 8.3191 6.7706 10.412 90 84.614 90 1.7871-111.5 Sheets Zigzag Ribbon No dimers Parallel Flat ai56 P21/c 4 11.653 6.7804 7.3707 90 87.942 90 1.7927-111.47 Sheets Zigzag Ribbon No dimers Parallel Flat ak29 P21/c 4 9.0659 6.7653 9.6395 90 96.733 90 1.777-111.4 Sheets Zigzag Ribbon No dimers Parallel Flat cc61 Pc 8 6.7749 9.2572 22.281 57.934 90 90 1.7622-111.36 Sheets Zigzag Ribbon Ladder Alternates cd7 P-1 8 13.32 6.796 14.261 90 113.61 90 1.7641-111.29 Chains 4,4-Grid NH ON al57 P2 4 11.213 4.8193 12.552 90 63.47 90 1.7192-111.11 Sheets 4,4-Grid No dimers NH ON No free D or A ak94 P21/c 4 10.641 5.5634 11.379 90 118.94 90 1.77-111.02 Sheets 4,4-Grid No dimers NIMFOE02 bh90 Pa 4 16.593 5.4105 6.8086 90 90 90 1.7069-110.94 Sheets Zigzag Ribbon No dimers Parallel Undulates cd54 P21 8 19.632 6.781 11.461 53.725 90 90 1.6966-110.83 Sheets Ladder Undulates Anti-Parallel bj78 Pn 4 18.051 6.7773 5.2213 90 112.93 90 1.7736-110.77 Sheets Zigzag Ribbon No dimers Anti-Parallel Flat af18 P21 2 5.4546 6.7902 7.9048 90 86.247 90 1.7857-110.61 Sheets Zigzag Ribbon No dimers Parallel Flat af35 P21 2 5.4324 6.7895 9.9248 90 126.98 90 1.7841-110.56 Sheets Zigzag Ribbon No dimers Parallel Flat ab41 P-1 2 4.8801 6.5666 19.08 32.033 69.683 70.683 1.72-110.5 Sheets Ladder Stepped Parallel dd30 C2/c 4 12.215 5.8027 17.498 90 91.145 90 1.6829-110.39 CrissCross Ladder dd25 C2/c 4 12.213 5.8121 17.489 90 91.274 90 1.6813-110.37 CrissCross Ladder cd82 Pbcn 8 8.6628 13.25 10.563 90 90 90 1.7212-110.03 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de15 C2/c 4 23.948 4.9574 19.015 90 33.474 90 1.676-110.02 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de86 P-1 4 19.089 6.8126 12.441 96.233 47.907 94.315 1.7485-109.74 Chains 4,4-Grid NH ON ai93 P21/c 4 11.669 6.5606 9.889 90 52.028 90 1.7483-109.57 Sheets 6,3-Net; Herringbone JESMAW Undulates ai57 P21/c 4 11.369 6.7856 8.914 90 120.1 90 1.7537-109.34 Sheets Zigzag Ribbon No dimers Anti-Parallel Flat af68 P21 2 6.6299 6.2114 7.0365 90 92.712 90 1.8024-109.29 Sheets 4,4-Grid No dimers Free O1 O2 bifurcated am25 P21/c 4 4.1816 12.927 11.087 90 92.455 90 1.7427-109.27 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A 28

da35 Cc 2 8.2332 6.7896 12.726 90 123.08 90 1.7505-109.24 Chains 4,4-Grid NH ON am46 P21/c 4 4.1764 12.931 11.104 90 92.533 90 1.7417-109.14 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am88 P21/c 4 5.3108 12.289 9.0938 90 97.443 90 1.7729-109.07 Chains 4,4-Grid NH ON ad56 P1 2 5.1394 14.048 6.7809 90.029 130.79 63.133 1.7534-108.88 Sheets Zigzag Ribbon No dimers Parallel Flat ca108 P-1 2 9.9906 7.0988 9.4637 139.02 126.28 45.328 1.6811-108.83 Sheets Symmetric Ribbon Non-Polar Parallel Flat de27 C2/c 4 29.008 3.7377 12.834 90 121.34 90 1.7558-108.82 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A (a) (b) Figure S2.9 The ribbons with no uracil-uracil dimer interactions can adopt either (a) a parallel arrangement as seen for ak97 (planar conformation) or (b) an anti-parallel arrangement as observed for bj78 (planar conformation) (C - dark grey; H - light grey; N - blue; O - red). Table S2.11 The low energy structures found for 5-fluorouracil Label S. G. Z a(å) b(å) c(å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis FURACL 01 P-1 8 8.6329 9.1560 12.5796 99.119 100.021 90.017 Sheets 4.8 2 Net FURACL 03 P21/c 4 5.0433 14.935 6.6049 90 108.884 90 Sheets Asymmetric Ribbon Undulates am75 P21/c Asymmetric Ribbon Undulates 4 5.3483 15.2630 6.5084 90 110.269 90 1.7336-102.49 Sheets am56 P21/n 4 6.0360 10.3935 9.1923 90 120.824 90 1.7447-102.40 Sheets Asymmetric Ribbon Stepped ca13 P-1 2 7.0329 6.7740 7.7005 110.151 127.289 96.846 1.7548-100.52 Sheets Symmetric Ribbon Non-Polar Parallel Flat am108 P21/n 4 6.2248 7.5378 12.8866 90 123.658 90 1.7167-100.34 Sheets Asymmetric Ribbon Undulates am93 P21/n 4 5.2646 9.1015 10.9730 90 105.564 90 1.7058-100.23 Sheets Asymmetric Ribbon Undulates 29

ca33 P-1 2 7.0204 5.4119 6.9556 100.861 98.174 79.619 1.7029-100.19 Sheets Symmetric Ribbon Non-Polar Parallel Flat ak24 P21/c 4 7.2451 7.0076 11.8396 90 122.614 90 1.7064-99.64 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat ak90 P21/c 4 7.3440 7.0295 9.9111 90 95.421 90 1.6962-99.26 Sheets Symmetric Ribbon Polar Parallel Flat am51 P21/n 4 4.9672 9.4660 11.0329 90 106.365 90 1.7359-99.11 CrissCross Asymmetric Ribbon aq61 P212121 4 6.9902 10.4365 6.9932 90 90 90 1.6935-98.99 Sheets Symmetric Ribbon Polar Anti-Parallel Undulates fa47 P21/c 4 7.6905 9.5535 10.2760 90 42.981 90 1.6786-98.96 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am36 P21/n 4 3.7370 11.2962 12.0717 90 102.420 90 1.7361-98.78 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dc71 C2/c 4 13.0795 5.1531 16.0088 90 107.638 90 1.6805-98.75 CrissCross Symmetric Ribbon Non-Polar aq90 P212121 4 11.5910 6.2724 7.0633 90 90 90 1.6825-98.60 Sheets Symmetric Ribbon Polar Parallel Flat fa20 P21/c 4 3.8158 20.6027 6.6778 90 106.773 90 1.7189-98.53 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc19 P21/c 4 5.5899 7.0256 13.3994 90 102.879 90 1.6843-98.49 Sheets Symmetric Ribbon Polar Anti-Parallel Flat am64 P21/c 4 4.4279 13.1036 8.4620 90 91.703 90 1.7605-98.35 Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A ab94 P-1 2 6.5991 3.9445 10.8665 112.507 87.099 105.825 1.7215-98.30 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab98 P-1 2 3.8535 6.6416 11.1322 68.617 92.179 73.795 1.7168-97.98 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab13 P-1 2 6.9188 5.4358 9.4747 100.133 79.639 134.075 1.7199-97.89 Sheets Symmetric Ribbon Non-Polar Parallel Flat ak39 P21/c 4 8.6869 6.9861 8.3732 90 93.165 90 1.7029-97.83 Sheets Symmetric Ribbon Polar Parallel Stepped am87 P21/n 4 3.7308 9.9739 13.9328 90 97.094 90 1.6794-97.76 CrissCross Asymmetric Ribbon de33 C2/c 4 12.7373 3.8415 20.6778 90 84.922 90 1.7146-97.76 CrissCross Symmetric Ribbon Non-Polar ai86 P21/c 4 9.6963 4.1286 12.5502 90 86.785 90 1.7224-97.74 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd73 C2/c 4 7.9534 6.8896 18.3215 90 94.104 90 1.7256-97.42 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat de93 C2/c 4 19.6358 6.9653 18.6958 90 23.428 90 1.6997-97.35 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat av64 Pna21 4 10.3806 7.1148 7.0005 90 90 90 1.6711-97.35 Sheets Symmetric Ribbon Polar Parallel Undulates fc65 P21/c 4 3.8435 5.5204 23.2735 90 88.228 90 1.7505-97.21 CrissCross Symmetric Ribbon Non-Polar fc25 P21/c 4 4.6088 5.2840 20.4191 90 88.077 90 1.7385-97.11 CrissCross Symmetric Ribbon Non-Polar dd26 C2/c 4 12.7899 3.8648 22.6326 90 115.109 90 1.7058-97.11 CrissCross Symmetric Ribbon Non-Polar de24 C2/c 4 18.7796 6.9671 17.3498 90 153.506 90 1.7064-97.06 Sheets Symmetric Ribbon Polar Anti-Parallel Stepped am115 P21/c 4 5.3004 11.9835 7.9757 90 89.464 90 1.7056-96.81 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc34 P21/n 4 5.1603 4.5159 23.4387 90 115.171 90 1.7478-96.79 CrissCross Symmetric Ribbon Non-Polar fc86 P21/c 4 4.3433 6.9612 16.7771 90 93.540 90 1.7065-96.79 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped fc59 P21/n 4 4.9834 4.5783 22.0314 90 86.084 90 1.7229-96.70 Sheets 6,3-Net IURACL10 fa5 P21/c 4 3.8620 22.9636 5.6422 90 88.571 90 1.7273-96.70 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ak3 P21/c 4 11.3745 3.8541 12.7091 90 116.051 90 1.7261-96.66 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fa30 P21/c 4 4.9550 19.2987 6.9146 90 49.590 90 1.7161-96.56 Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca23 P-1 2 6.7037 3.7814 12.4202 71.793 72.786 57.075 1.7427-96.52 Sheets Symmetric Ribbon Non-Polar Parallel Stepped 30

Table S2.12 The low energy structures found for 5-chlorouracil Label S. G. Z a(å) b(å) (Å) α( ) β( ) γ( ) Density (g cm -3 ) L. E. (kj mol -1 ) Motif Analysis 5-Chloro P21/c 4 8.4393 6.8412 10.9631 90 124.067 90 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped ak41 P21/c 4 7.1028 12.2181 7.3658 90 122.748 90 1.8104-111.91 Sheets Symmetric Ribbon Non-polar Parallel Flat da3 Cc 2 6.9097 12.2317 12.4264 90 149.169 90 1.8082-111.61 Sheets Symmetric Ribbon Polar Parallel Flat fc26 P21/n 4 5.6890 7.0006 14.2406 90 105.058 90 1.7771-110.58 Sheets Symmetric Ribbon Polar Anti-parallel Stepped ak108 P21/c 4 8.3787 7.0133 11.2719 90 124.274 90 1.7782-110.55 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped ca66 P-1 2 6.9947 5.7738 6.8918 99.826 87.202 90.469 1.7766-110.44 Sheets Symmetric Ribbon Non-polar Parallel Stepped ak55 P21/c 4 7.0854 7.0196 11.0624 90 96.763 90 1.7813-110.27 Sheets Symmetric Ribbon Polar Parallel Stepped ab158 P-1 2 7.0130 6.5645 8.0689 101.071 127.541 98.097 1.7843-110.07 Sheets Symmetric Ribbon Non-polar Parallel Flat ca99 P-1 2 7.0903 7.0303 6.8542 66.764 59.487 79.859 1.8001-109.94 Sheets Symmetric Ribbon Non-polar Parallel Flat ca164 P-1 2 6.7231 6.9732 7.5431 57.718 100.297 115.217 1.8029-109.93 Sheets Symmetric Ribbon Non-polar Parallel Flat ca117 P-1 2 6.9783 9.3991 7.4951 137.342 119.215 54.844 1.7991-109.93 Sheets Symmetric Ribbon Non-polar Parallel Flat aq82 P212121 4 12.3164 6.3972 7.0510 90 90 90 1.7519-108.92 Sheets Symmetric Ribbon Polar Parallel Flat ai55 P21/c 4 7.7255 6.9550 10.0965 90 92.816 90 1.7962-108.86 Sheets Symmetric Ribbon Polar Parallel Stepped ca114 P-1 2 6.9385 6.0843 7.6571 91.896 91.740 122.869 1.7964-108.51 Sheets Symmetric Ribbon Non-polar Parallel Stepped fc103 P21/n 4 8.9527 7.0109 9.4619 90 66.435 90 1.7879-108.49 Sheets Symmetric Ribbon Polar Anti-parallel Stepped af9 P21 2 5.5897 6.9818 7.1250 90 97.279 90 1.7643-108.40 Sheets Symmetric Ribbon Polar Parallel Stepped fa154 P21/c 4 5.7201 12.6723 7.2559 90 92.963 90 1.8530-108.39 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat dd79 C2/c 4 12.3285 6.4316 14.0261 90 91.086 90 1.7506-108.39 Sheets Symmetric Ribbon Non-polar Parallel Flat de4 C2/c 4 18.0323 6.9379 15.4941 90 146.019 90 1.7967-108.32 Sheets Symmetric Ribbon Polar Anti-parallel Stepped de9 C2/c 4 18.3020 6.9654 15.7989 90 147.204 90 1.7943-108.30 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped dd31 C2/c 4 9.9716 6.9564 15.7343 90 92.656 90 1.7854-108.22 Sheets Symmetric Ribbon Polar Anti-parallel Stepped aj20 P2/c 4 7.9260 6.9558 18.3014 90 32.808 90 1.7803-108.01 Sheets Symmetric Ribbon Non-polar Parallel Stepped am121 P21/c 4 5.9617 7.8788 13.4449 90 55.958 90 1.8599-107.99 Dimers N1 O1 dimers NH Cl 6,3-Net ai60 P21/c 4 11.4748 3.9898 12.7307 90 111.494 90 1.7947-107.87 Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de29 C2/c 4 10.0037 6.9465 18.9811 90 124.169 90 1.7837-107.75 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped db1 C2 2 9.9056 6.9555 7.9440 90 92.400 90 1.7798-107.65 Sheets Symmetric Ribbon Polar Parallel Stepped fc166 P21/c 4 5.5718 7.0060 14.3043 90 97.401 90 1.7577-107.54 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped dc36 C2/c 4 12.7568 4.0624 21.5418 90 82.104 90 1.7604-107.53 CrissCross Symmetric Ribbon Non-polar am135 P21/n 4 5.6453 9.3904 10.9832 90 107.316 90 1.7510-107.26 Sheets Asymmetric Ribbon Undulates ab6 P-1 2 3.9272 6.6472 11.2793 76.353 99.837 105.633 1.7778-106.94 Sheets Symmetric Ribbon Non-polar Parallel Stepped 31

Density (g cm -3 ) 1.34 1.36 1.38 1.4 1.42 1.44 1.46 1.48 1.5-104 Density (g cm -3 ) 1.36 1.38 1.4 1.42 1.44 1.46 1.48-104 -105-105 -106-107 -108-109 -110 H 2 C Lattice Energy (kj mol -1 ) O H H N N H O -106-107 -108-109 -110 Lattice Energy (kj mol -1 ) O H CH 2 H N N H O (a) (b) -108 Density (g cm -3 ) 1.6 1.62 1.64 1.66 1.68 1.7 1.72 1.74 1.76 1.78 1.8 1.82 1.84 1.86 1.88 Density (g cm -3 ) 1.66 1.68 1.7 1.72 1.74 1.76 1.78 1.8 1.82-108 -109-109 -110-111 -112-113 -114-115 -116-117 -118-119 NO 2 O H Lattice Energy (kj mol -1 ) N N H H O -110-111 -112-113 -114-115 -116-117 -118-119 NO 2 O H Lattice Energy (kj mol -1 ) N N H H O (c) (d) 32

Density (g cm -3 ) 1.62 1.64 1.66 1.68 1.7-123 Density (g cm -3 ) 1.62 1.64 1.66 1.68 1.7 1.72 1.74 1.76 1.78-96 -124-97 -125-126 -127 Lattice Energy (kj mol -1 ) -128-129 O H NH 2 H N N O H -98-99 -100-101 Lattice Energy (kj mol -1 ) (e) (f) Sheets of Polar Parallel Symmetric Ribbons Sheets of Non-Polar Parallel Symmetric Ribbons Sheets of Polar Anti-Parallel Symmetric Ribbons Sheets of Non-Polar Anti-Parallel Symmetric Ribbons Polar Symmetric Ribbons (not sheets) Non-Polar Symmetric Ribbons (not sheets) Sheets of Asymmetric Ribbons Asymmetric Ribbons (not sheets) 6,3-Net Same Motif as 5-(Diphenylphosphino)uracil Same Motif as Nitrouracil/1,4-Dioxane Solvate Based on the Iodouracil Motif 6,3-Net (ESI Figure S2.3a) Based on the Nitrouracil form III Motif Sheets of Parallel Ladders Sheets of Anti-Parallel Ladders Sheets of Parallel Ribbons Sheets of Anti-Parallel Ribbons Ladders (not sheets) Sheets of alternating Ribbons and Ladders 4,4-Grid 3D Chains Dimers Figure S2.10 Plots of lattice energy against density with the unique structures denoted by the motif adopted when just considering the hydrogen bonding interactions formed by the uracil. The structures corresponding to the known forms are indicated by red open shapes. (a) 5-Vinyluracil with the CH2 group over the carbonyl at C4, (b) 5-vinyluracil with the CH2 group over the hydrogen at C6, (c) 5-nitrouracil, using the gas phase ab initio optimized conformation, (d) 5-nitrouracil, using the constrained planar conformation for NO2, (e) 5-aminouracil and (f) 5-fluorouracil. -102-103 O H F N N O H H 33

3. Details and results of the manual crystallization experiments Where possible, analysis of the product was performed by single crystal X-ray diffraction. Microcrystalline products were looked at by powder X- ray diffraction and the powder pattern obtained was compared visually with those simulated for any known forms. Table S3.1 Summary of the results of the crystallizations performed on each of the 5-substituted uracils. Compound Uracil Thymine No. of Crystallizations 13 Evaporation 3 Evaporation (at 5 C) Method Solvents Results Acetone 2-Chloroethanol 1,4-Dioxane Ethanol Ethyl acetate Methanol 2,2,2-Trifluoroethanol Water and mixtures of the above 1,4-Dioxane Methanol Water Microcrystalline product Microcrystalline product 1 Evaporation Water Hydrate (blocks) + Known form (needles) 1 Evaporation Acetone Known form (blocks) 2 Evaporation Dimethyl formamide Methanol Known form (plates / needles) 1 Evaporation Ethanol Known form (microcrystalline) 5 Evaporation Hydrochloric acid Methanol + Acetone Methanol + Ethanol Nitromethane Known form (plates) 1,4-Dioxane 3 Evaporation Propan-1-ol Tetrahydrofuran Known form (needles) 34

20 Evaporation Acetonitrile Butan-2-ol n-butyl ether t-butyl methyl ether Chloroform Cyclohexane Dichloromethane Diethyl ether Diethyl oxalate Di-isopropyl ether Dimethylamine Ethyl acetate Ethyl methyl ketone Hexane Hydrobromic acid n-octane Propan-2-ol Toluene 2,2,2-Trifluoroethanol o-xylene microcrystalline / no solid product 1 Evaporation (at 5 C) Propan-1-ol Known form (plates) 1 Evaporation (at 5 C) Tetrahydrofuran Known form (microcrystalline) 1 Evaporation (at 5 C) Water Hydrate (blocks) 1 Evaporation (at 5 C) Methanol Hydrate (blocks) + Known form plates) 1 Vapour diffusion Ethanol : Chloroform No solid product 2 Vapour diffusion Ethanol : Toluene Methanol : Toluene Known form (plates) 1 Vapour diffusion Ethanol : Di-isopropyl ether Microcrystalline 2 Vapour diffusion Methanol : Chloroform Methanol : Di-isopropyl ether Microcrystalline needles 5-Vinyluracil 20 Evaporation Acetone Acetonitrile Chloroform Cyclohexane Dimethyl sulphoxide Microcrystalline / No solid product 35

5-Iodouracil 6 Cooling (to 5 C) 1,4-Dioxane Ethanol Methanol Propan-2-ol Tetrahydrofuran 2,2,2-Trifluoroethanol Water and mixtures of the above Acetone Acetonitrile Ethanol Methanol 2,2,2-Trifluoroethanol Water No solid product 1 Sublimation No solid product 18 Evaporation 3 Evaporation (at 5 C) Acetone 2-Chloroethanol 1,4-Dioxane Ethanol Ethyl acetate Methanol Propan-1-ol Propan-2-ol 2,2,2-Trifluoroethanol Water Butan-1-ol Ethanol Propan-2-ol Known form (blocks and needles) Known form (blocks and needles) 36

5-Ethyluracil 8 Evaporation 5-Cyanouracil 8 Evaporation Acetone Acetonitrile Chloroform 1,4-Dioxane Ethanol Propan-2-ol Water and mixtures of the above 1 Slow cooling of a hot solution Water + Acetone New form (lath) Acetone Acetonitrile Chloroform 1,4-Dioxane Ethanol Propan-2-ol Microcrystalline blocks and needles New form (blocks) 5-Chlorouracil 1,4-Dioxane 3 Evaporation Methanol Water 3 Evaporation (at 5 C) 1,4-Dioxane Methanol Water Known form (plates) Known form (plates) 5-Bromouracil 1 Evaporation 1,4-dioxane Known form (blocks) 5-Aminouracil 17 Evaporation Acetone Acetonitrile Chloroform Cyclohexane Dimethyl sulphoxide 1,4-Dioxane Ethanol Methanol Propan-2-ol Tetrahydrofuran microcrystalline / no solid product 37

and mixtures of the above 8 Cooling (to 5 C) Acetone Acetonitrile Cyclohexane 1,4-Dioxane Ethanol Methanol 2,2,2-Trifluoroethanol Water 1 Sublimation no solid product Microcrystalline / No solid product 38

4. Crystal Structures 4.1 5-Ethyluracil Figure S4.1 The labelling scheme used for 5-ethyluracil. Displacement ellipsoids are drawn at the 50% probability level. 39

(a) (b) Figure S4.2 Packing diagram illustrating (a) the sheets of non-polar parallel symmetric ribbons and (b) the stacking of parallel sheets (C - dark grey; H - light grey; N - blue; O - red). 40

4.2 5-Cyanouracil Figure S4.3 The labelling scheme used for 5-cyanouracil. Displacement ellipsoids are drawn at the 50% probability level. 41

4.3 5-Fluorouracil Benzamide solvate (1/1) Figure S4.4 The labelling scheme used for 5-fluorouracil benzamide solvate. Displacement ellipsoids are drawn at the 50% probability level. (a) (b) Figure S4.5 Packing diagram illustrating (a) the sheets of by alternating rows of benzonitrile and 5-fluorouracil symmetric ribbons and (b) the stacking of parallel sheets (C - dark grey; H - light grey; N - blue; O - red; F - light green). 42

4.4 5-Fluorouracil Formamide solvate (1/1) Figure S4.6 The labelling scheme used for 5-fluorouracil formamide solvate. Displacement ellipsoids are drawn at the 50% probability level. 43

(a) (b) Figure S4.7 Packing diagram illustrating (a) the sheets formed by 5-fluorouracil formamide solvate and (b) the stacking of parallel sheets (C - dark grey; H - light grey; N - blue; O - red; F - light green). 4.5 5-Chlorouracil Figure S4.8 The labelling scheme used for 5-chlorouracil and illustrating the disorder model with the major component shown with black bonds and the minor component with white bonds. Displacement ellipsoids are drawn at the 50% probability level. 44

(a) (b) Figure S4.9 Packing diagram illustrating, for just the major component (a) the sheets of non-polar anti-parallel symmetric ribbons and (b) the stacking of parallel sheets (C - dark grey; H - light grey; N - blue; O - red; Cl - green). 45

4.6 5-Bromouracil Figure S4.10 The labelling scheme used for 5-bromouracil and illustrating the disorder model with the major component shown with black bonds and the minor component with white bonds. Displacement ellipsoids are drawn at the 50% probability level. (a) (b) Figure S4.11 Packing diagram illustrating, for just the major component (a) the sheets of non-polar anti-parallel symmetric ribbons and (b) the stacking of parallel sheets (C - dark grey; H - light grey; N - blue; O - red; Br - brown). 46