A study of 5-substituted uracils

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1 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 catena-((μ3-uracil-5-carboxylato-o,o,o,o')-( ACUFOU 4.24 Cc 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 catena-((μ5-uracil-5-carboxylato- ACUGAH 2.14 P2 1/c O,O,O,O',O',O',O'')-(μ3-aqua)-rubidium) Metal catena-((μ6-hydrogen bis(uracil-5- ACUGEL 2.35 P carboxylato))-diaqua-cesium) Metal ADOSBU 8.3 P Adenosine-5-bromouracil APSURD 4.1 P alpha-pseudouridine monohydrate 2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5- AYEBIP 4.5 P21/c 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 BIKHIN 0 P Fluorouracil 2,2,2-trifluoroethanol No Co-ordinates BIKHIN P Fluorouracil 2,2,2-trifluoroethanol solvate BOMMOF 5.8 P Uracilylmethyl-triphenylphosphonium chloride ethanolsolvate monohydrate 1

2 BRURAC01 0 P* Bromouracil No Co-ordinates BRURAC P21/c Bromouracil CLURAC P21/c Chlorouracil CYSTYM 4.3 P alpha-s-cysteinylthymine hydrochloride CYSURC P S-Cysteinyluracil monohydrate CYTFUR 16.2 P CYTFUR P DAVGAI 5.42 P 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 FORHAV 3.6 P21/c (Diphenylphosphino)uracil Higher R Higher T No H FURACL 9.2 P Fluorouracil FURACL P Fluorouracil FURACL P2 1/c Fluorouracil Higher R Higher T FURACL P2 1/c Fluorouracil FURACL04 0 P Fluorouracil No Co-ordinates FURACL05 0 P Fluorouracil No Co-ordinates FURACL06 0 P Fluorouracil No Co-ordinates FURACL07 0 P Fluorouracil No Co-ordinates FURACL08 0 P Fluorouracil No Co-ordinates FURACL09 0 P Fluorouracil No Co-ordinates FURACL10 0 P Fluorouracil No Co-ordinates FURACL11 0 P Fluorouracil No Co-ordinates FURACL12 0 P Fluorouracil No Co-ordinates FURACL13 0 P Fluorouracil No Co-ordinates FUREHX 5.5 P21/c Fluorouracil-9-ethylhypoxanthine FURMCY 9.4 Pbca Fluorouracil-1-methylcytosine complex GAGTAK 3.5 P (Ethisteron-21-yl)uracil GEHCIF 3.4 P21/n GONHOG 4 P Dicarbonyl-nitrosyl-(5- diphenylphosphinouracil-p)-cobalt methanol solvate Metal 1,4-Dideoxy-1,4-imino-1-beta-(5-uracilyl)-Llyxitol hydrochloride 2

3 HONRAD 5.1 P ,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 P IURACL P Iodouracil (1,2-bis(Amidino-O-methylurea)ethane)- copper(ii) thymine bis(tetrafluoroborate) monohydrate Metal IVOROA 5.63 P JEFWAT 3.69 C2/c Fluoropyrimidine-2,4(1H,3H)-dione JEFWAT C2/c Fluoropyrimidine-2,4(1H,3H)-dione Higher R Higher T JEFWAT C2/c Fluoropyrimidine-2,4(1H,3H)-dione Higher R JESMAW 6.88 P2 1/n Nitrouracil hemikis(dioxane) JESMEA 6.36 P Nitrouracil piperazine 5-Nitrouracil hemikis(n,n'- dimethylpiperazine) JESMIE P JESMOK 4.74 P2 1/c Nitrouracil pyridine JESMUQ 4.39 P2 1/c Nitrouracil bis(formamide) JESNAX 7.54 P2 1/c Nitrouracil ethanol hemihydrate JESNEB P2 1/c Nitrouracil 3-aminopyridine 5-Nitrouracil 1,4-diazabicyclo(2.2.2)octane JESNIF 5.84 P2 1/c hydrate KEWJUS 6.17 P Malayamycin A monohydrate LAFTOC 3.39 P2 1/m LAFTUI 3.39 P2 1/m LAFVAQ 4.83 P LAFVEU 4.95 C2/c 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

4 LAFVIY 4.31 C2/c LAFVOE 2.54 C2/c LICCEG 2.97 P LUXHIV 7.27 P2 1/n 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 NIMFOE 3.63 P2 1/n Nitrouracil NIMFOE Pbca Nitrouracil NIMFOE P Nitrouracil NIMGAR 2.97 P2 1/n Nitrouracil dimethyl sulfoxide solvate NIMGAR P2 1/n Nitrouracil dimethylsulfoxide Higher R NURAMH 6 P2 1/c Nitrouracil monohydrate Diaqua-bis(2,4-dioxopyrimidin-5- carboxylato)-copper(ii) PABREQ 7.36 P2 1/n PAHHOW 5.21 P Fluorouracil 1,4-dioxane PAHHUC 4.85 P2 1/n Fluorouracil dimethylformamide PAHJAK 3.63 P2 1/c Fluorouracil dimethylsulfoxide PAHJAK01 0 P2 1/c Fluorouracil dimethylsulfoxide No Co-ordinates QARWAI 4.09 P Hydroxyuracil QARWEM 0 Pna Hydroxyuracil dimethylsulfoxide solvate No Co-ordinates 5-beta-D-Ribofuranosyl-2,4(1H,3H)- ROKYUL 9.18 P pyrimidinedione 5-(1-(3-Methoxycarbonyl-Oethylpseudoureido))uracil SABNOY 4.1 C2/c (1-(3-Methoxycarbonyl-Sethylpseudothioureido))uracil SABNUE 3.4 P21/n

5 Potassium (N,N'-bis(acetato)-N,N'-bis(N''- uracil-5-ylacetamido)-1,2-ethylenediamine)- SOQZUT 5.8 P21/n dioxo-vanadiumpentahydrate Metal (N,N'-bis(Acetato)-N,N'-bis(N''-uracil-5- ylacetamido)-1,2- SORBOQ 5.7 C2/c ethylenediamine)-aqua-zinc tetrahydrate Metal Diaqua bis(1,2,3,4-tetrahydro-2,4-dioxo-5- TAGVOM 3.31 P2 1/n pyrimidinecarboxylato)-manganese(ii) Metal THYBNZ Pcmn Thymine-p-benzoquinone complex THYMEL 0 P21/c Thymine N,N-diethylmelamine monohydrate No Co-ordinates THYMIN 14.9 P2 1/c Thymine Higher R No H THYMIN P2 1/c Thymine THYMMH 7.8 P2 1/c Thymine monohydrate TUGMEN 5.33 P (beta-D-Arabinofuranosyl)uracil No Co-ordinates UGUMUE 4.94 R (Trifluoromethyl)uracil URACIL 4.5 P21/a Uracil URACIL P2 1/a Uracil No Co-ordinates URILHG 9.3 P bis(uracil) mercury(ii) chloride complex Metal catena-((μ2-aqua)-(μ2-5-carboxyuracil)- lithium) Metal VEYVUQ 3.09 P2 1/n catena-((μ2-5-uracilmethyl hydrogen phosphonato)-bis(μ2-aqua)-diaqua-sodium WASSOZ 4.74 P monohydrate) Metal catena-(bis(μ2-5-uracilmethyl hydrogen phosphato)-tris(μ2-aqua)-diaqua-dipotassium) WASSUF 4.28 C2/c Metal WESRAN 6 P2 1/c bis(6-carboxyuracil)-diaqua-zinc(ii) Metal WEWTAU 3.1 P WUYGIG 2.66 P2 1/c WUYGOM 5.77 P2 1/c WUYGUS 7.9 P2 1/c XOJXID 5.2 P 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

6 XOJXOJ 6.8 P21/c 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 YAZRAS 3.35 P 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 ZUNYIQ 7.8 P Diaqua-bis(iso-orotato)-iron dihydrate Metal 6

7 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 P Ethisteron-21-yl Dimers N3(H) O2 dimers; N1(H) interacts with R ADOSBU P Br Adenosine No interactions with itself All interactions to adenosine BRURAC10 P21/c 4 1 Br Symmetric ribbon (disorder not modelled) UGUMUE R CF3 3-D N2(H) O2 dimers linked by N1(H) O1; have CF3 rich regions BOMMOF P 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 P 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 F Dioxane Chains N3(H) O2 dimers and N3(H) O1 dimers linked into chains by N1(H) O1 singles CYTFUR01 P 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 F 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 P I 4,4-grid N1(H) O1 single; N2(H) O1 single; HONRAE P L-Penitol HCl Symmetric ribbon Anti-parallel polar GONHOG P Lyxitol HCl Chains N1(H) O2 interactions KEWJUS P 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 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 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

8 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 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 P NO 2 4,4-grid N1(H) O1 + N2(H) O2 (all single) QARWAI P 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 P 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 P Psuedouridine H2O No interactions with itself All uracil to tail or H2O interactions ROKYUL P1 2 2 Psuedouridine Symmetric ribbon Parallel polar CYSURC10 P CH2SCH2C(COO)NH3 H2O Symmetric ribbon Parallel polar CYSTYM P 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 JESMEA P Piperazine NURAMH P21/c 4 1 H2O 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 JESMAW P21/n 4 1 Dioxane JESMIE P Dimethylpiperazine JESNIF P21/c 8 2 DABCO, H2O -2.28; JESNEB P21/c Aminopyridine NIMFOE P21/n NIMFOE01 Pbca NIMFOE02 P

9 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 and one with the NO2 group constrained to be in the same plane as the uracil. 9

10 (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 Sheets 6,3-Net; Brickwall URACIL Free O1 Flat da12 Cc Sheets Symmetric Ribbon Polar Parallel Flat ai46 P21/c Sheets Symmetric Ribbon Polar Parallel Flat cd105 P Sheets Symmetric Ribbon Polar Parallel Flat am100 P21/c Sheets Asymmetric Ribbon Flat ca96 P Sheets Symmetric Ribbon Non-Polar Parallel Flat am36 P21/n Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates ca59 P Sheets Symmetric Ribbon Non-Polar Parallel Flat ab72 P Sheets Symmetric Ribbon Non-Polar Parallel Flat am10 P21/c Sheets Symmetric Ribbon Non-Polar Parallel Flat aj39 P2/c Sheets Symmetric Ribbon Non-Polar Parallel Flat cb99 Pbca Sheets Asymmetric Ribbon Flat am2 P21/c Sheets Asymmetric Ribbon Flat dc6 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ak38 P21/c Sheets Symmetric Ribbon Polar Parallel Flat cb66 P Sheets 6,3-Net; Brickwall URACIL Free O1 Flat fa23 P Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ay96 P Sheets Symmetric Ribbon Polar Parallel Flat ab40 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped de95 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Flat 10

11 am7 P21/c Sheets 6,3-Net; Brickwall URACIL Free O1 Flat dd16 P Sheets Asymmetric Ribbon Flat fa29 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am81 P21/c Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates fc82 P21/c CrissCross Symmetric Ribbon Non-Polar cb100 Pca Sheets Symmetric Ribbon Polar Parallel Undulates dd49 C2/c Sheets Symmetric Ribbon Polar Parallel Flat fc91 P21/c CrissCross Symmetric Ribbon Non-Polar am82 P21/c Sheets 6,3-Net; Brickwall URACIL Free O1 Flat cd7 Pbcn Sheets Asymmetric Ribbon Stepped cc34 P Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates cc33 P Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fa31 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am65 P21/c Sheets Asymmetric Ribbon Stepped av17 Pc CrissCross Asymmetric Ribbon dc27 C2/c CrissCross Symmetric Ribbon Non-Polar fa15 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ap38 P Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A au79 Pna CrissCross Symmetric Ribbon Polar cd1 Pbcn Sheets Symmetric Ribbon Non-Polar Parallel Undulates ca17 P Sheets Asymmetric Ribbon Flat cb64 P Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates fc51 P21/n Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ab44 P Sheets Asymmetric Ribbon Flat ad41 Pc Sheets Symmetric Ribbon Non-Polar Parallel Undulates fc47 P21/n Sheets 6,3-Net; Herringbone JESMAW Flat au19 Pna CrissCross Symmetric Ribbon Polar ak45 P21/c Sheets Symmetric Ribbon Non-Polar Parallel Stepped fa50 P21/c Sheets 6,3-Net; Herringbone JESMAW Undulates bf65 Pc Sheets 6,3-Net; Herringbone O2 Dimer Undulates ce29 Pc Sheets Symmetric Ribbon Non-Polar Parallel Stepped av8 Pna D be13 Pnn CrissCross Symmetric Ribbon Polar ay13 Pa D 11

12 ak44 P21/c 4 IURACL Sheets Symmetric Ribbon Polar Anti-Parallel Stepped af76 P Sheets Symmetric Ribbon Polar Parallel Stepped ak75 P21/c Sheets 6,3-Net Free O2 Undulates dc53 C2/c CrissCross Symmetric Ribbon Non-Polar aj30 P2/c Sheets Asymmetric Ribbon Flat ai41 P21/c Sheets 6,3-Net Free O2 Undulates am72 P21/c Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A cc2 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates am28 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am75 P21/n Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates am4 P21/n Sheets 6,3-Net; Brickwall URACIL Free O1 Undulates cc93 Pca Sheets 6,3-Net Free O2 Undulates da104 Cc D cd86 Pbcn Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A cd81 P Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A aq5 P Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd87 C2/c Sheets 6,3-Net; Herringbone JESMAW Flat ap78 P D de20 C2/c Sheets 6,3-Net Free O2 Undulates ak15 P21/c Sheets Asymmetric Ribbon Flat fc42 P21/n Sheets 6,3-Net; Herringbone JESMAW Undulates de39 C2/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd102 P Sheets 6,3-Net; Brickwall URACIL Free O1 Flat ar70 Pnn Sheets Asymmetric Ribbon Stepped ar11 Pnn D cb11 P Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A af7 P Sheets 4,4-grid IURACL10 cb53 P Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A fa87 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc60 Pc Sheets Symmetric Ribbon Non-Polar Parallel Undulates ad3 Pc Sheets Symmetric Ribbon Polar Parallel Undulates av67 P Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A av23 P Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A aq73 P Sheets 4,4-grid 12

13 ak16 P21/c Sheets 6,3-Net; Herringbone JESMAW Flat fc90 P21/c Sheets 6,3-Net; Herringbone O2 Dimer Undulates bb19 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulates av62 Pna D bb55 P D aj1 P Sheets Symmetric Ribbon Non-Polar Parallel Undulates ce45 Pbcn Sheets Symmetric Ribbon Polar Anti-Parallel Undulates av40 Pna D bd56 Pna D fc79 P21/c Sheets 6,3-Net; Herringbone JESMAW Flat de82 C2/c Sheets 6,3-Net; Herringbone JESMAW Flat fc5 P21/c Sheets 4,4-grid IURACL10 fc35 P21/n Sheets 4,4-grid IURACL10 bh24 Pa Sheets Symmetric Ribbon Polar Parallel Undulates 13

14 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 S Z a(å) b(å) α( ) β( ) γ( ) c(å) The low energy structures found for thymine 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).

15 dc19 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped aj11 P2/c Sheets Symmetric Ribbon Non-Polar Parallel Stepped dd37 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ad53 Pc Sheets Symmetric Ribbon Polar Parallel Flat fa7 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates au9 Pna CrissCross Symmetric Ribbon Polar ca24 P Sheets Symmetric Ribbon Non-Polar Parallel Flat bj91 P CrissCross Symmetric Ribbon Polar bg101 Pc Sheets Symmetric Ribbon Polar Anti-Parallel Undulating ba88 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulating bj34 P CrissCross Symmetric Ribbon Polar be13 Pc CrissCross Symmetric Ribbon Polar dd58 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Undulates da63 Cc Sheets Symmetric Ribbon Polar Parallel Flat dd57 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Undulates cb117 Pca Sheets Symmetric Ribbon Polar Parallel Flat aq7 P Sheets Symmetric Ribbon Polar Parallel Flat ce64 Pbcn Sheets Symmetric Ribbon Polar Anti-Parallel Undulates aj71 P Sheets Asymmetric Ribbon Stepped db37 C Sheets Symmetric Ribbon Polar Parallel Stepped cc51 Pca Sheets 6,3-Net Free O2 Undulates am8 P21/c Sheets Symmetric Ribbon Non-Polar Parallel Flat ai115 P21/c Sheets 6,3-Net Free O2 Undulates fa1 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates av11 P Sheets Symmetric Ribbon Polar Parallel Flat ak38 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped ai81 P21/c Sheets 6,3-Net Free O2 Undulates ab65 P Sheets Asymmetric Ribbon Stepped dd8 C2/c CrissCross Symmetric Ribbon Non-Polar fc123 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped dd10 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Flat ak104 P21/c Sheets 6,3-Net Free O2 Undulates am7 P21/c Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A al76 Pc CrissCross Asymmetric Ribbon 15

16 fa103 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ak41 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Flat dd42 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Undulates am5 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulating No free D or A ai92 P21/c Sheets 6,3-Net Free O2 Undulates db32 C Sheets Symmetric Ribbon Non-Polar Parallel Undulates db31 C Sheets Symmetric Ribbon Non-Polar Parallel Undulates dd124 C2/c 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 Sheets Symmetric Ribbon Non-Polar Parallel Flat ab38 P Sheets Symmetric Ribbon Non-Polar Parallel Flat dd88 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Flat ak6 P21/c Sheets Symmetric Ribbon Polar Parallel Flat ca106 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped fc18 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc22 P21/n CrissCross Symmetric Ribbon Non-Polar fa44 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc78 P21/n Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat am44 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am85 P21/c Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A dd6 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc76 P21/n CrissCross Symmetric Ribbon Non-Polar ab107 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ai90 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped ca86 P Sheets Asymmetric Ribbon Stepped dd101 C2/c CrissCross Symmetric Ribbon Non-Polar dc64 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fa71 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Undulates ca103 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped cc38 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates 16

17 ab72 P Sheets Asymmetric Ribbon Stepped dd42 C2/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped da63 Cc Sheets Symmetric Ribbon Polar Parallel Flat ce87 Pbcn Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates dc50 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ai88 P21/c CrissCross Asymmetric Ribbon ak76 P21/c Sheets Zigzag Ribbon No dimers Parallel Flat ai36 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped fa74 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca79 P Sheets Asymmetric Ribbon Flat db36 C Sheets Symmetric Ribbon Polar Parallel Stepped fa102 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca111 P Sheets Asymmetric Ribbon Flat ak37 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped af19 P Sheets Symmetric Ribbon Polar Parallel Flat au61 Pna CrissCross Symmetric Ribbon Polar am101 P21/n Sheets Asymmetric Ribbon Stepped ad109 Pc 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 Sheets Symmetric Ribbon Polar Parallel Flat ak91 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ak83 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped ca105 P Sheets Symmetric Ribbon Non-polar Parallel Stepped ca95 P Sheets Symmetric Ribbon Non-polar Parallel Flat de49 C2/c Sheets Symmetric Ribbon Polar Parallel Flat ca103 P Sheets Symmetric Ribbon Non-polar Parallel Stepped fc36 P21/n Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de30 C2/c CrissCross Symmetric Ribbon Non-polar ak2 P21/c Sheets 6,3-Net Free O2 Undulates af78 P Sheets Symmetric Ribbon Polar Parallel Stepped fa9 P21/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates 17

18 fa61 P21/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates fc86 P21/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped af74 P Sheets Symmetric Ribbon Polar Parallel Stepped ay115 P Sheets Symmetric Ribbon Polar Parallel Stepped fc100 P21/n CrissCross Symmetric Ribbon Non-polar fc54 P21/n Sheets Symmetric Ribbon Polar Anti-Parallel Stepped ab34 P Sheets Symmetric Ribbon Non-polar Parallel Flat cc107 Pca Sheets Symmetric Ribbon Polar Parallel Undulates fc99 P21/n CrissCross Symmetric Ribbon Non-polar fc80 P21/n CrissCross Symmetric Ribbon Non-polar fc29 P21/n Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped am88 P21/n Sheets Symmetric Ribbon Non-polar Parallel Flat fc12 P21/n CrissCross Symmetric Ribbon Non-polar cc28 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates ce81 P Sheets Symmetric Ribbon Polar Parallel Flat fa64 P21/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates ak9 P21/c Sheets 6,3-Net Free O2 Undulates aj64 P Sheets Symmetric Ribbon Polar Parallel Flat fc9 P21/n Sheets Symmetric Ribbon Non-polar Parallel Undulates bg79 Pc Sheets Symmetric Ribbon Polar Anti-Parallel Stepped da20 Cc Sheets Symmetric Ribbon Polar Parallel Flat cd14 Pbcn Sheets Symmetric Ribbon Non-polar Anti-Parallel Undulates az23 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulates ca90 P Sheets Symmetric Ribbon Non-polar Parallel Stepped dc13 C2/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Flat de77 C2/c CrissCross Symmetric Ribbon Non-polar ak56 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped aq42 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulates au29 Pna CrissCross Symmetric Ribbon Polar ai80 P21/c Sheets 6,3-Net Free O2 Undulates dc91 C2/c CrissCross Symmetric Ribbon Non-polar ar76 Pc CrissCross Symmetric Ribbon Polar dd52 C2/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Flat ad41 Pc Sheets Symmetric Ribbon Polar Parallel Flat 18

19 de103 C2/c Sheets Symmetric Ribbon Non-polar Parallel Stepped dc22 C2/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped dc66 C2/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de52 C2/c Sheets Symmetric Ribbon Polar Parallel Flat ak60 P21/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped de61 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped cc50 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates dd35 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped au53 Pna Sheets Symmetric Ribbon Polar Parallel Undulates db68 C Sheets Symmetric Ribbon Polar Parallel Stepped de42 C2/c Sheets Symmetric Ribbon Non-polar Anti-Parallel Stepped am25 P21/c Sheets Symmetric Ribbon Non-polar Parallel Flat dd34 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped az38 P Sheets 4,4-Grid IURACL10 fa102 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Undulates dd90 C2/c CrissCross Symmetric Ribbon Non-polar db31 C Sheets Symmetric Ribbon Polar Parallel Stepped ce24 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulates af100 P Sheets 4,4-Grid IURACL10 inverted cd74 P Sheets Symmetric Ribbon Polar Parallel Undulates ak90 P21/c Sheets Symmetric Ribbon Non-polar Parallel Stepped af111 P Sheets 4,4-Grid IURACL10 inverted cc95 Pca Sheets Symmetric Ribbon Non-polar Parallel Undulates fc50 P21/c Sheets 4,4-Grid IURACL10 am143 P21/c Sheets 4,4-Grid IURACL10 ab65 P 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 Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab61 P Sheets Asymmetric Ribbon Flat fc16 P21/n CrissCross Symmetric Ribbon Non-Polar cd73 Pbcn Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates 19

20 fa19 P Sheets Symmetric Ribbon Polar Anti-Parallel Stepped bj52 Pn CrissCross Symmetric Ribbon Polar cc125 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates am103 P21/c Sheets Symmetric Ribbon Non-Polar Parallel Stepped fc18 P21/n CrissCross Symmetric Ribbon Non-Polar fa21 P Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates da20 Cc Sheets Symmetric Ribbon Polar Parallel Undulates dd11 C2/c Sheets Symmetric Ribbon Non-Polar Parallel Undulates be51 Pc CrissCross Symmetric Ribbon Polar ca95 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ad69 Pc Sheets Symmetric Ribbon Polar Parallel Flat ai112 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped am124 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ca39 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ca27 P Sheets Symmetric Ribbon Non-Polar Parallel Flat ca106 P Sheets Symmetric Ribbon Non-Polar Parallel Flat ai97 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped ak87 P21/c Sheets Symmetric Ribbon Polar Parallel Flat dd18 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped fc92 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Flat cc33 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates cc127 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates cc64 Pbca Sheets Symmetric Ribbon Polar Parallel Undulates am74 P21/n CrissCross Asymmetric Ribbon al20 P2/c Sheets Symmetric Ribbon Non-Polar Parallel Stepped av25 P Sheets Symmetric Ribbon Polar Parallel Stepped ai33 P21/c Sheets 6,3-Net; Herringbone JESMAW Undulates de45 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Flat dd22 P Sheets Asymmetric Ribbon Stepped dc80 P Sheets Asymmetric Ribbon Stepped dc77 C2/c CrissCross Symmetric Ribbon Non-Polar am111 P21/c CrissCross Asymmetric Ribbon dc75 Cc CrissCross Symmetric Ribbon Non-Polar ce49 Pca Sheets Symmetric Ribbon Polar Anti-Parallel Undulates 20

21 ak56 P21/c 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 Sheets Ladder Flat Anti-Parallel au93 Anti-Parallel Pc Dimers N3 O1 dimers NH N(C) 6,3-Net am109 P21/n Dimers N3 O2 dimers NH N(C) 3-D cb140 Pbca Chains 4,4-Grid NH N(C) ak31 P21/c Sheets Ladder Flat am34 P21/n Dimers N3 O1 dimers NH N(C) 6,3-Net aj67 P Chains 4,4-Grid NH N(C) am64 P21/n Dimers N1 O1 dimers NH N(C) 6,3-Net am44 P21/n Sheets Asymmetric Ribbon Undulates as26 Pna Chains 4,4-Grid NH N(C) aj18 Pc Dimers N1 O1 dimers NH N(C) 6,3-Net cb66 P Dimers N1 O1 dimers NH N(C) 6,3-Net ay74 Pc None NH N(C) only 3-D av73 Pna Chains 3-D NH N(C) cd125 Pna Chains 4,4-Grid NH N(C) am55 P21/c Dimers N1 O1 dimers NH N(C) 6,3-Net cd69 Pc Chains 4,4-Grid NH N(C) ag26 Pc Chains 4,4-Grid NH N(C) av52 Pna Chains 3-D NH N(C) am22 P21/n Dimers N3 O1 dimers NH N(C) 6,3-Net as44 Pna Chains 3-D NH N(C) bd2 P Dimers N1 O1 dimers NH N(C) 6,3-Net am68 P21/c Chains 4,4-Grid NH N(C) cc82 P21/b Chains 4,4-Grid NH N(C) ab24 P Sheets Ladder Stepped Parallel da1 Cc Chains 4,4-Grid NH N(C) ax3 Pn Chains 4,4-Grid NH N(C) ai96 P21/c Chains 4,4-Grid NH N(C) ay45 Pca None NH N(C) only 3-D 21

22 am27 P21/c Dimers N1 O1 dimers NH N(C) 6,3-Net ca78 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped al97 P2/c Chains 4,4-Grid NH N(C) am66 P21/c Dimers N3 O1 dimers NH N(C) 6,3-Net am43 P21/c Chains 4,4-Grid NH N(C) am57 P21/n Dimers N3 O1 dimers NH N(C) 6,3-Net ao10 P Sheets Ladder Stepped Parallel am54 P21/n 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

23 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).

24 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 Sheets Symmetric Ribbon Non-Polar Parallel Flat am88 P21/n Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers av76 P Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers av38 Pna Dimers N3 O1 dimers NH OH 3-D cd47 P21/n Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers ca15 P Sheets Symmetric Ribbon Non-Polar Parallel Flat am39 P21/c Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers cb57 P Dimers N3 O1 dimers NH OH 4,4-Grid OH O2 dimers cd51 Pbcn 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 Dimers N3 O2 dimers N1 NH2 3-D NH2 O1 am131 P21/n Dimers N1 O1 dimers N3 NH2 3-D NH2 O2 dimers am57 P21/c Dimers N3 O1 dimers N1 NH2 3-D NH2 O2 dimers fc35 P21/n CrissCross Symmetric Ribbon Non-Polar bd74 Pna CrissCross Symmetric Ribbon Polar 24

25 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 Sheets Asymmetric Ribbon? NIMFOE 01 Pbca Sheets Asymmetric Ribbon Stepped NIMFOE 02 P Sheets 4,4-Grid No dimers NIMFOE02 am112 P21/n Dimers N1 O1 dimers NH ON 6,3-Net fa74 P21/c Sheets Ladder Undulates Anti-Parallel ab33 P Sheets Ladder Flat Parallel de9 C2/c CrissCross Ladder am124 P21/n Dimers N3 O1 dimers NH ON 6,3-Net aq62 P Sheets 4,4-Grid No dimers NIMFOE02 am101 P21/c Sheets Asymmetric Ribbon Stepped db56 C Sheets 4,4-Grid No dimers NH ON No free D or A ca100 P Sheets Ladder Stepped Parallel dd65 C2/c Sheets 4,4-Grid No dimers NH ON No free D or A aw43 P D ai56 P21/c Sheets 6,3-Net; Herringbone JESMAW Undulates al56 Pc Sheets Ladder Flat Anti-Parallel ab95 P Sheets Asymmetric Ribbon Flat ak15 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ca45 P Sheets Asymmetric Ribbon Flat fa97 P21/c Sheets Ladder Undulates Anti-Parallel de27 C2/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab16 P Sheets Symmetric Ribbon Non-Polar Parallel Flat fa96 P21/c Sheets Ladder Undulates Anti-Parallel ai47 P21/c Sheets Ladder Flat Parallel dc79 C2/c CrissCross Ladder aq22 P Chains 4,4-Grid NH ON dd42 C2/c Sheets Asymmetric Ribbon Flat ak52 P21/c Sheets Ladder Flat Anti-Parallel au44 Pna Chains 4,4-Grid NH ON 25

26 ak42 P21/c 4 Undulates Anti-Parallel Sheets Zigzag Ribbon No dimers Parallel Flat am19 P21/n Dimers N3 O2 dimers NH ON 3-D am80 P21/n Dimers N3 O1 dimers NH ON 6,3-Net * DHA = 119 ai94 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc21 P21/c CrissCross Ladder cc76 Pca Sheets Ladder Undulates Parallel fa15 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates cd1 Pbcn Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab39 P Sheets Ladder Flat Parallel av25 Pna Sheets 4,4-Grid No dimers NIMFOE02 cb107 Pbca Sheets Asymmetric Ribbon Stepped ab40 P Sheets Ladder Flat Parallel cc100 Pca Sheets Ladder de104 C2/c CrissCross Ladder cd39 Pbcn Sheets Asymmetric Ribbon Flat am55 P21/c Sheets Asymmetric Ribbon Stepped cb90 Pbca Sheets Asymmetric Ribbon Undulates am22 P21/n Sheets Ladder Undulates Parallel de54 C2/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de43 C2/c CrissCross Ladder am27 P21/c CrissCross Asymmetric Ribbon ba38 P Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates fa58 P Sheets 4,4-Grid No dimers NH ON No free D or A dc89 C2/c Sheets Zigzag Ribbon No dimers Anti-Parallel Stepped de97 C2/c CrissCross Ladder af66 P Sheets 6,3-Net IURACL10 af40 P Sheets 6,3-Net IURACL10 cc70 Pbca Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ai53 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am67 P21/c Chains 4,4-Grid NH ON am65 P21/n Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd43 Pna Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A cd8 P Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ab120 P Sheets Symmetric Ribbon Non-Polar Parallel Flat 26

27 ak62 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc59 P21/n Sheets Ladder Flat Anti-Parallel am105 P21/c Sheets Asymmetric Ribbon Flat de98 C2/c Dimers N3 O1 dimers NH ON 6,3-Net ai46 P21/c Sheets Zigzag Ribbon No dimers Parallel Stepped ai30 P21/c Sheets Zigzag Ribbon No dimers Anti-Parallel Stepped da51 Cc Chains 4,4-Grid NH ON * DHA = 128 cb79 Pbca 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 Sheets Asymmetric Ribbon? NIMFOE 01 Pbca Sheets Asymmetric Ribbon Stepped NIMFOE 02 P Sheets 4,4-Grid No dimers NIMFOE02 aq24 P Sheets 4,4-Grid No dimers NIMFOE02 cb93 P21/c Sheets 6,3-Net No dimers NH ON No free D or A ca85 P Sheets Ladder Flat Parallel fc77 P21/n Sheets Ladder Flat Anti-Parallel 27

28 bb70 P Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates dc62 C2/c Sheets Ladder Flat Anti-Parallel fa64 P Sheets Ladder Undulates Anti-Parallel az91 P Sheets Zigzag Ribbon No dimers Anti-Parallel Undulates fa10 P Sheets Ladder Undulates Anti-Parallel am51 P21/n Dimers N3 O1 dimers NH ON 6,3-Net dc1 C2/c Sheets 4,4-Grid No dimers NH ON No free D or A am14 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A ai54 P21/c Chains 4,4-Grid NH ON dd59 C2/c CrissCross Ladder ai90 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd26 C2/c CrissCross Ladder ak97 P21/c Sheets Zigzag Ribbon No dimers Parallel Flat ai56 P21/c Sheets Zigzag Ribbon No dimers Parallel Flat ak29 P21/c Sheets Zigzag Ribbon No dimers Parallel Flat cc61 Pc Sheets Zigzag Ribbon Ladder Alternates cd7 P Chains 4,4-Grid NH ON al57 P Sheets 4,4-Grid No dimers NH ON No free D or A ak94 P21/c Sheets 4,4-Grid No dimers NIMFOE02 bh90 Pa Sheets Zigzag Ribbon No dimers Parallel Undulates cd54 P Sheets Ladder Undulates Anti-Parallel bj78 Pn Sheets Zigzag Ribbon No dimers Anti-Parallel Flat af18 P Sheets Zigzag Ribbon No dimers Parallel Flat af35 P Sheets Zigzag Ribbon No dimers Parallel Flat ab41 P Sheets Ladder Stepped Parallel dd30 C2/c CrissCross Ladder dd25 C2/c CrissCross Ladder cd82 Pbcn Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de15 C2/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de86 P Chains 4,4-Grid NH ON ai93 P21/c Sheets 6,3-Net; Herringbone JESMAW Undulates ai57 P21/c Sheets Zigzag Ribbon No dimers Anti-Parallel Flat af68 P Sheets 4,4-Grid No dimers Free O1 O2 bifurcated am25 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A 28

29 da35 Cc Chains 4,4-Grid NH ON am46 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A am88 P21/c Chains 4,4-Grid NH ON ad56 P Sheets Zigzag Ribbon No dimers Parallel Flat ca108 P Sheets Symmetric Ribbon Non-Polar Parallel Flat de27 C2/c 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 Sheets Net FURACL 03 P21/c Sheets Asymmetric Ribbon Undulates am75 P21/c Asymmetric Ribbon Undulates Sheets am56 P21/n Sheets Asymmetric Ribbon Stepped ca13 P Sheets Symmetric Ribbon Non-Polar Parallel Flat am108 P21/n Sheets Asymmetric Ribbon Undulates am93 P21/n Sheets Asymmetric Ribbon Undulates 29

30 ca33 P Sheets Symmetric Ribbon Non-Polar Parallel Flat ak24 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat ak90 P21/c Sheets Symmetric Ribbon Polar Parallel Flat am51 P21/n CrissCross Asymmetric Ribbon aq61 P Sheets Symmetric Ribbon Polar Anti-Parallel Undulates fa47 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates am36 P21/n Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dc71 C2/c CrissCross Symmetric Ribbon Non-Polar aq90 P Sheets Symmetric Ribbon Polar Parallel Flat fa20 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates fc19 P21/c Sheets Symmetric Ribbon Polar Anti-Parallel Flat am64 P21/c Sheets 6,3-Net; Brickwall FORHAV Flat No free D or A ab94 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab98 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped ab13 P Sheets Symmetric Ribbon Non-Polar Parallel Flat ak39 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped am87 P21/n CrissCross Asymmetric Ribbon de33 C2/c CrissCross Symmetric Ribbon Non-Polar ai86 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A dd73 C2/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat de93 C2/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Flat av64 Pna Sheets Symmetric Ribbon Polar Parallel Undulates fc65 P21/c CrissCross Symmetric Ribbon Non-Polar fc25 P21/c CrissCross Symmetric Ribbon Non-Polar dd26 C2/c CrissCross Symmetric Ribbon Non-Polar de24 C2/c Sheets Symmetric Ribbon Polar Anti-Parallel Stepped am115 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fc34 P21/n CrissCross Symmetric Ribbon Non-Polar fc86 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Stepped fc59 P21/n Sheets 6,3-Net IURACL10 fa5 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ak3 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A fa30 P21/c Sheets Symmetric Ribbon Non-Polar Anti-Parallel Undulates ca23 P Sheets Symmetric Ribbon Non-Polar Parallel Stepped 30

31 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 Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped ak41 P21/c Sheets Symmetric Ribbon Non-polar Parallel Flat da3 Cc Sheets Symmetric Ribbon Polar Parallel Flat fc26 P21/n Sheets Symmetric Ribbon Polar Anti-parallel Stepped ak108 P21/c Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped ca66 P Sheets Symmetric Ribbon Non-polar Parallel Stepped ak55 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped ab158 P Sheets Symmetric Ribbon Non-polar Parallel Flat ca99 P Sheets Symmetric Ribbon Non-polar Parallel Flat ca164 P Sheets Symmetric Ribbon Non-polar Parallel Flat ca117 P Sheets Symmetric Ribbon Non-polar Parallel Flat aq82 P Sheets Symmetric Ribbon Polar Parallel Flat ai55 P21/c Sheets Symmetric Ribbon Polar Parallel Stepped ca114 P Sheets Symmetric Ribbon Non-polar Parallel Stepped fc103 P21/n Sheets Symmetric Ribbon Polar Anti-parallel Stepped af9 P Sheets Symmetric Ribbon Polar Parallel Stepped fa154 P21/c Sheets 6,3-Net; Brickwall URACIL Free O1 Flat dd79 C2/c Sheets Symmetric Ribbon Non-polar Parallel Flat de4 C2/c Sheets Symmetric Ribbon Polar Anti-parallel Stepped de9 C2/c Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped dd31 C2/c Sheets Symmetric Ribbon Polar Anti-parallel Stepped aj20 P2/c Sheets Symmetric Ribbon Non-polar Parallel Stepped am121 P21/c Dimers N1 O1 dimers NH Cl 6,3-Net ai60 P21/c Sheets 6,3-Net; Brickwall FORHAV Undulates No free D or A de29 C2/c Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped db1 C Sheets Symmetric Ribbon Polar Parallel Stepped fc166 P21/c Sheets Symmetric Ribbon Non-polar Anti-parallel Stepped dc36 C2/c CrissCross Symmetric Ribbon Non-polar am135 P21/n Sheets Asymmetric Ribbon Undulates ab6 P Sheets Symmetric Ribbon Non-polar Parallel Stepped 31

32 Density (g cm -3 ) Density (g cm -3 ) H 2 C Lattice Energy (kj mol -1 ) O H H N N H O Lattice Energy (kj mol -1 ) O H CH 2 H N N H O (a) (b) -108 Density (g cm -3 ) Density (g cm -3 ) NO 2 O H Lattice Energy (kj mol -1 ) N N H H O NO 2 O H Lattice Energy (kj mol -1 ) N N H H O (c) (d) 32

33 Density (g cm -3 ) Density (g cm -3 ) Lattice Energy (kj mol -1 ) O H NH 2 H N N O H 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 O H F N N O H H 33

34 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

35 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

36 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

37 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

38 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

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

40 (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

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

42 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

43 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

44 (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) 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

45 (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

46 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