The observed and energetically feasible crystal structures of 5-substituted uracils

Barnett, Sarah A.; Hulme, Ashley T.; Issa, Nizar; Lewis, Thomas C.; Price, Louise S.; Tocher, Derek A.; Price, Sarah L.

doi:10.1039/b806763e

Cited by 43 publications

(58 citation statements)

References 69 publications

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“…All non-conventional interactions belong to intramolecular interactions. In the packing of molecules in crystal each molecule of ligand is bonded to two neighbouring molecules with intermolecular hydrogen bonding with D-A distance of 2.09(2) Å in N(5)-H(5NA)ÁÁÁO(3) and 2.99(2) Å in N(6)-H(6NA)ÁÁÁO (2). Interlinkage of the molecules through this way provide one dimensional chain architecture in which intramolecular hydrogen bonding and non-conventional hydrogen bonding (Table 3) are further used for the stabilization of the structure.…”

Section: Crystal Descriptionsmentioning

confidence: 99%

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An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

et al. 2012

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Uracil, one of the four RNA bases is a vital component in the complex processes of molecular genetics. The correct functioning of these processes depends on the types of bonds formed by uracil with the surroundings. This communication elaborates the versatile potential of 1,3-dimethyl-6-aminouracil (L 1 ) to form its 5-, 6-position substituted derivatives with different significant molecular packing behaviours. Presently, five crystals (L 2 -L 6 ) have been synthesised and their crystallographic architectures are glimpsed in this paper. Analysis of crystal packing shows supra-molecular behaviours through hydrogen bonding and p-p interactions among the molecules in maintaining the integrity of the structures. The ligand 6,6'-diamino-1,1',3,3'-tetramethyl-5,5'-(benzylidene)bis[pyrimidine-2,4(1H,3H)-dione] was observed to be stabilised in a helical arrangement.

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Section: Crystal Descriptionsmentioning

confidence: 99%

“…This promoted a brief experimental search for new polymorphic forms [2]. It is also one of the five nuceobases and therefore an important component of nucleic acids.…”

Section: Introductionmentioning

confidence: 99%

An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

et al. 2012

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“…The difference in the intrinsic basicity of the two carbonyl moieties, caused by the substituent at the 5-position, [63][64][65][66] can account for a variety of hydrogen bonded motifs involving conventional HBs. 14,40 Due to the electron-deficient moieties in the heterocyclic ring, the less acidic hydrogen atoms at the sp 3 hybridized carbons 67,68 are able to form weak C-H … O interactions and, to a smaller extent, also C-H … X interactions. [69][70][71][72] At the moment, DMHU and DMXUs are not well studied in the solid state.…”

Section: Introductionmentioning

confidence: 99%

“…In pure IU and 5-bromouracil (BrU), the crystal packing is controlled entirely by conventional HBs as the molecules do not manifest XBs. 14,40 In the XB and HB survey by Ho and co-workers, 6 and in a later survey performed on more than 600 hits, 11 it has been shown that, when HBs and XBs share a common oxygen atom, the C=O ... X angle is commonly found close to 120°. 6 This result is consistent with lone-pair directionality similar to that frequently observed for hydrogen donors involved in conventional and unconventional hydrogen bonding to sp 2 hybridized oxygen atoms.…”

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confidence: 99%

Role of Weak Hydrogen Bonds and Halogen Bonds in 5-Halo-1,3-dimethyluracils and Their Cocrystals—A Combined Experimental and Computational Study

Portalone

Moilanen

Tuononen

2016

Crystal Growth & Design

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Seven single crystals containing either N,N-dimethyluracil (DMHU) or one of its 5-halogenated derivatives (DMXU; X = F, Cl, Br, I) were prepared using N,Ndimethylformamide as the crystallization solvent. Single crystal X-ray diffraction and quantum chemical calculations carried out at the spin component scaled local MP2 level of theory were then used to study the intramolecular halogen and non-conventional hydrogen bonds present in the structures. The results were compared to and contrasted with the previously reported data for uracil and its halogenated derivatives. In particular, the intermolecular interactions in DMIU were compared to the halogen and hydrogen bonds in 5-iodouracil that, in contrast to DMHU and its derivatives, displays conventional hydrogen bonds involving its strong N-H donor sites.The crystallographic and computational analyses showed that, while non-conventional hydrogen bonds are present in both DMHU and DMXU, halogen bonds could only be identified in DMBrU and DMIU, in which case they play an important role in directing the resulting crystal structures.2

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“…In the particularly striking case of thymine, slurrying experiments in 27 organic solvents all yielded the known forms [105,106]. However, subsequent sublimation experiments almost a decade later produced a new stable polymorph, and further dehydration experiments found two more previously unknown forms [106].…”

Section: Screening For New Solid Formsmentioning

confidence: 99%

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

Dybeck

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AcknowledgementsI would like to acknowledge the guidance and support provided by my advisor MichaelShirts. I would also like to thank Levi Naden, Natalie Schieber, Nate Abraham and the entire Shirts group for their help and technical support during my research. I also would like to acknowledge the UVA high performance computing team for the computational resources necessary to complete this work. Finally, I would like to acknowledge the endless love and support that my friends and family provided me during this challenging Ph.D. journey.iii AbstractThe presence of multiple stable crystal structures in solid organic materials can limit their commercial viability when two or more observable polymorphs exhibit markedly different physical properties. Unintended restructuring events have hindered pharmaceutical solid form development in numerous therapeutic candidates and have led to costly market recalls.Conversely, intentional synthesis of a metastable form has led to significantly more favorable performance in numerous materials.Current computational methods for predicting polymorphic behavior evaluate candidate crystal structures based on the minimized lattice energy. However, these static lattice energybased approaches generate far more lattice energy minima than there are experimentally observed structures. Thermal motion of the crystals under working conditions has the potential to explain why many of these lattice minima are not observed experimentally. Lattice minima that are identified from a static crystal structure prediction can ultimately be unstable at experimental conditions through either temperature-mediated stability reranking, kinetic interconversion of multiple minima, or inaccuracies of the energy function in producing the real crystal ensemble.In this work, we explore the role of thermal motion in eliminating candidate crystal structures using fully atomistic molecular dynamics simulations. Enthalpically favorable structures with low entropy will become unfavorable at high temperatures through temperaturemediated stability reranking. Our simulations correctly identify the high temperature solid form as having a larger entropy than the low temperature form in twelve small molecule organic systems with known temperature-mediated transformations. The estimated entropy differences in the classical point-charge potential are significantly closer to experimental measurements than estimated enthalpy differences. This result suggests that entropy difference estimates are less sensitive to the complexity of the simulation potential than the corresponding enthalpy estimates. We additionally find that a cheaper harmonic approximation provides a sufficient estimate of entropic contributions in small rigid molecules. However, entropies with iv the harmonic approximation diverge from molecular dynamics-derived entropies in systems with multiple rotatable degrees of freedom or dynamically disordered crystalline structures.We additionally probe the sensitivity of the stability estimates to the energy function ...

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The observed and energetically feasible crystal structures of 5-substituted uracils

Cited by 43 publications

References 69 publications

An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

Role of Weak Hydrogen Bonds and Halogen Bonds in 5-Halo-1,3-dimethyluracils and Their Cocrystals—A Combined Experimental and Computational Study

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

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