Several medicinally important compounds carry a 2-(thiazol-2-yl)guanidine unit. These species are generally (erroneously) represented as 1-(thiazol-2-yl)guanidine species. Quantum chemical studies were performed to identify the appropriate tautomeric state of this class of compounds. B3LYP/6-31+G(d) calculations indicate the preferred tautomeric state of these species is associated with the 2-(thiazol-2-yl)guanidine structure rather than the 1-(thiazol-2-yl)guanidine structure. G2MP2 calculations on the model system were carried out to study the electronic structure, electron delocalization, and protonation energy; MESP, ELF, HOMA, AIM, and NBO analyses were also carried out. The results indicate that this class of compounds may be treated as species with hidden ::N(←L)R character. Upon protonation of the thiazole ring nitrogen, these systems show the electronic structure as in ::N(←L)2(⊕) systems with divalent N(I) oxidation state.

Several medicinally important compounds carry benzimidazole carbamate moiety. In the scientific literature, these molecules are represented in different tautomeric forms. In this report, conformational and tautomeric preferences were analyzed on the model benzimidazole carbamate (carbendazim), so as to understand the potential energy surface of the title compounds. Quantum chemical calculations have been performed using HF, B3LYP, and MP2 methods in gas phase and solvent phase on model benzimidazole carbamate to understand the conformational and tautomeric preferences. (1) PE surface of amide-imide tautomers, (2) electron distribution, (3) AIM analysis, (4) NBO charges, (5) 1,3-H shift, etc., have been investigated for carbendazim and its conformers. The molecular electrostatic potential (MESP) surfaces of carbendazim have been studied. Further to understand the polymorphism in benzimidazole carbamate, analysis of dimers of carbendazim has been carried out. The results indicate that a neglected tautomer is important and the tautomeric equilibrium is quite subtle in these systems and it should be extensively considered in all studies related to these drugs.

Quantum chemical calculations have been performed using HF, B3LYP, and MP2 methods on the model sulfonylurea PhSO(2)NHC(=O)NHMe to understand the conformational and tautomeric preferences. The results indicate that a conformer with intramolecular hydrogen bond SLU-1 (hitherto not considered) is more stable than the conformer SLU-2 (which is generally considered) for sulfonylureas. The energy difference between these two conformers is about 4 kcal/mol in the gas phase; however, the energy differences between the two rotamers become negligible in the solvent phase. Iminol tautomeric forms of sulfonylurea (which were also not studied until now) are only about 5-6 kcal/mol higher in energy as per both gas-phase and solvent-phase analyses, indicating easy accessibility of tautomeric states in sulfonylureas. Quantum chemical analysis has also been carried out on the possible dimeric structures of these three important isomers of sulfonylurea, and correlations have been made to the known crystal structures of polymorphic states of sulfonylurea drugs.

Optically active mandelic acid in the presence of dimethylaminopyridine is an excellent chiral shift reagent for the determination of enantiomeric excess and absolute configuration in cyanohydrins.

We have shown that a structure as simple as an ion pair of (R)- or (S)-mandelate and dimethylamminopyridinium ions possesses structural features that are sufficient for NMR enantiodiscrimination of cyanohydrins. Moreover, (1)H NMR data of cyanohydrins of known configuration obtained in the presence of the mandelate-dimethylaminopyridinium ion pair point to the existence of a correlation between chemical shifts and absolute configuration of cyanohydrins. Mandelate-DMAPH(+) ion pair and mandelonitrile form a 1:1 complex with an association constant of 338 M(-1) (DeltaG(0), -3.4 kcal/mol) for the (R)-mandelonitrile/(R)-mandelate-DMAPH(+) and 139 M(-1) (DeltaG(0), -2.9 kcal/mol) for the (R)-mandelonitrile/(S)-mandelate-DMAPH(+) complex. To understand the origin of enantiodiscrimination, the geometry optimization and energy minimization of the models of ternary complexes of (S)-mandelonitrile/(R)-mandelate/DMAPH(+) and (S)-mandelonitrile/(S)-mandelate/DMAPH(+) complexes was performed using DFT methodology (B3LYP) with the 6-31+G(d) basis set in Gaussian 3.0. Further, analysis of optimized molecular model obtained from theoretical studies suggested that (i) DMAP may be replaced with other amines, (ii) the hydroxyl group of mandelic acid is not necessary for stabilization of ternary complex and may be replaced with other groups such as methyl, (iii) the ion pair should form a stable ternary complex with any hydrogen-bond donor, provided its OH bond is sufficiently polarized, and (iv) alpha-H of racemic mandelic acid should also get resolved with optically pure mandelonitrile. These inferences were experimentally verified, which not only validated the proposed model but also led to development of a new chiral solvating agent for determination of ee of carboxylic acids and absolute configuration of aryl but not alkyl carboxylic acids.