title: Intra- and intermolecular interactions in small bioactive molecules: cooperative features from experimental and theoretical charge-density analysis.
abstract: The topological features of the charge densities, rho(r), of three bioactive molecules, 2-thiouracil [2,3-dihydro-2-thioxopyrimidin-4(1H)-one], cytosine [4-aminopyrimidin-2(1H)-one] monohydrate and salicylic acid (2-hydroxybenzoic acid), have been determined from high-resolution X-ray diffraction data at 90 K. The corresponding results are compared with the periodic theoretical calculations, based on theoretical structure factors, performed using DFT (density-functional theory) at the B3LYP/6-31G** level. The molecules pack in the crystal lattices via weak intermolecular interactions as well as strong hydrogen bonds. All the chemical bonds, including the intra- and intermolecular interactions in all three compounds, have been quantitatively described by topological analysis based on Bader's quantum theory of 'Atoms In Molecules'. The roles of interactions such as C-H...O, C-H...S, C-H...pi and pi...pi have been investigated quantitatively in the presence of strong hydrogen bonds such as O-H...O, N-H...O and N-H...S, based on the criteria proposed by Koch and Popelier to characterize hydrogen bonds and van der Waals interactions. The features of weak intermolecular interactions, such as S...S in 2-thiouracil, the hydrogen bonds generated from the water molecule in cytosine monohydrate and the formation of the dimer via strong hydrogen bonds in salicylic acid, are highlighted on a quantum basis. Three-dimensional electrostatic potentials over the molecular surfaces emphasize the preferable binding sites in the structure and the interaction features of the atoms in the molecules, which are crucial for drug-receptor recognition.
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Parthapratim
authors.initials: P
authors.lastname: Munshi
authors.forename: Tayur N
authors.initials: TN
authors.lastname: Guru Row
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods / Q000706:statistics & numerical data; D003596:Cytosine / Q000737:chemistry; D004563:Electrochemistry / Q000379:methods* / Q000706:statistics & numerical data; D008958:Models, Molecular; D015394:Molecular Structure; D020156:Salicylic Acid / Q000737:chemistry; D012984:Software; D055672:Static Electricity; D013889:Thiouracil / Q000737:chemistry
chemical_list: D013889:Thiouracil; D003596:Cytosine; D020156:Salicylic Acid