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The 8-hydroxyquinoline (8HQ) molecule and its four derivatives used as medicines: chloroxine , clioquinol , iodoquinol , and nitroxoline (8HQ substituted in the benzene ring by 5,7-dichloro-, 5-chloro-7-iodo-, 5,7-diiodo-, and 7-nitro-, respectively), were studied using the DFT/B3LYP/6-311G∗∗ method. Three forms of each molecule were considered: (OH⋯N) with the intramolecular OH⋯N hydrogen bond, (OH;N) with the broken intramolecular hydrogen bond, and (NH), the tautomer with the H-atom attached to the pyridine N-atom. Regardless of the substitution, the (OH⋯N) form, with the intramolecular OH⋯N hydrogen bond, was the most stable form. Breaking the intramolecular bond led to the formation of (OH;N), which was less stable by at least 25 kJ/mol. The NH tautomer was higher in energy than the (OH⋯N) tautomer by at least 40 kJ/mol. Based on AIM analysis, it was found that the intramolecular OH⋯N bond was the weakest in 8HQ, stronger in chloroxine , clioquinol and iodoquinol , and it was the strongest in nitroxolin. The benzene ring aromaticity decreased from 8HQ, through halogenosubstituted 8HQ, to nitroxoline , which was in line with the decrease of the π-electron population in the benzene ring. The sum of aromaticities of the two rings was largest for the (OH⋯N) tautomers, significantly lower for the (OH;N) tautomers, and the smallest for (NH) tautomers. From the electron population in σ and π valence orbitals of the two quinoline rings it appears that, for the benzene ring, the halogens acted as σ-electron withdrawing and π-electron donating substituents, whereas NO 2 was a σ- and π-electron withdrawing substituent. The σ substituent effect almost solely influenced the substitution site, i.e., the benzene ring, whereas the π substituent effect was extended to the pyridine ring. Here, we also present changes in the σ and π-electron populations resulting from tautomerization and breaking of the intramolecular OH⋯N hydrogen bonds.

Chiral quaternary ammonium salts, catalysts for chiral Darzens reaction of α-chloroacetic acid esters with benzaldehyde to yield glycidates in phase-transfer catalysis conditions, were studied by using the DFT/B3LYP/6-31G∗∗ calculations. Structure and energetics of several complexes between the chiral Darzens reaction catalysts and α-haloacetic ester carboanion were examined. Based on comparison of the complex stabilization energies and experimental ee values it was shown that the complex interaction energy alone is not a crucial parameter for catalyst to be efficient in asymmetric synthesis. A catalyst design was also tried, however, despite the interaction energy for the designed catalyst increased the geometrical arrangement of the reactant and the catalyst favoured a racemic rather than an asymmetric reaction.

The side-chain mechanisms of alkylation of toluene by ethene over basic catalysts were modeled at the DFT/UB3LYP/6-311++G** level. The basic catalysts were modeled either by the Na radical atom or by the Na2 molecule. Comparison of the reaction paths for radical and non-radical mechanisms running on metals (Na or Na2) shows that the radical mechanism is disfavored by both thermodynamics and kinetics.

The 1-deazapurine molecules substituted by the NO 2 group at three different positions of the six-membered ring were subject of computational study performed at the B3LYP/cc-pVTZ level. For each substitution three tautomers were considered. The N3H tautomers are relatively instable in the gas and water phases which is due to significant decrease in aromaticity of the N3H forms. In the gas phase, the equilibria between the N7H and N9H tautomers are determined by a competition of the repulsive and attractive intermolecular interaction of different moieties of Nitro-1-deazapurine. The close neighborhood of the two tertiary N atoms and attractive close neighborhood of the tertiary N atom and the NH group result in preference of the N9H tautomer over the N7H one by ca. 3.5 kcal/mol. By comparing energy of different forms and proposed isodesmic reaction we showed that the Gibbs free energy of the attractive interaction between the NO 2 and HN groups is equal to ca. 1.0 kcal/mol, whereas the repulsive interaction between the NO 2 group and the tertiary N atom of the imidazole is equal to ca. 6.4 kcal/mol. It was shown also that the increase in dipole moment in the water media is the crucial effect influencing the N7H/N9H tautomeric equilibria of Nitro-1-deazapurines. For the three isomers dissolved in water, the two tautomers, N7H and N9H, are predicted to be observed and the former should dominate slightly for the 2-Nitro isomer whereas the latter for the 6-Nitro and 1-Nitro isomers. The NBO analysis showed that the NO 2 group withdraws 0.3 e of the σ-electrons from the pyridine ring of 1-deazapurine and has no influence on the σ-electrons of the imidazole ring. The NBO analysis shows also that the ratio between number of π-electrons which are withdrawed from imidazole vs. pyridine ring is characteristic for position of the substitution. The isodesmic reaction used revealed also that the NO 2 group destabilizes the N3H-1-deazapurine system, whereas it stabilizes the N7H- and N9H-1-deazapurine systems.

More than 30 guanazole tautomers, conformers, and zwitterions were calculated at the B3LYP/aug-cc-pVDZ level in vacuum and in water solution described by the IEF-PCM method. The most stable four structures were recalculated at the B3LYP/aug-cc-pVTZ level. The 1H guanazole tautomer appeared to be the only one stable in vacuum. The 4H tautomer, next stable in vacuum, is higher in energy by ca. 9.5 kcal/mol. In water (described by the IEF-PCM method), the 4H tautomer remains less stable by ca. 4.5 kcal/mol and the next most stable tautomers are disfavored by about 9 kcal/mol. Possibility of existence of and interconversion between two 1H conformers, which differ in direction of lone electron pairs of the two NH2 groups, was also considered. The interconvertion can proceed either by inversion or by rotation of one of the NH2 groups. The barrier for the invertion is only 100 cm−1 and it is overcome by the NH2 group inversion vibrational modes. Thus such a barrier is apparent rather than real. Barrier to the NH2 group rotation is equal to ca. 6 kcal/mol, and would preserve a given molecular conformation; however, the NH2 group inversion modes make this impossible. The autotropic proton shift between the two neighboring N atoms of the triazole ring was also considered; yet, the barrier for such a shift is ca. 40 kcal/mol high and is very unlikely.

The Darzens reaction leading to α,β-epoxy esters was modelled at the B3LYP/aug-cc-pVDZ level. Experimentally, the reaction proceeds at boundary between two phases, water and a non-polar, therefore, the two environments were considered in the simulations. The calculations show the Darzens reaction to be a stepwise process both in the gas phase and in solvents (toluene, acetonitrile, and water). In all considered environments, the first barrier, TS1, associated with formation of an intermediate, is much higher than TS2 associated with the closing of the epoxy ring with the simultaneous Cl− ion release. Therefore, the first process is the rate limiting step of the reaction. TS1 is the lowest for the gas phase, next in toluene, whereas the highest in acetonitrile and water. The same holds true for the small TS2 barrier which is especially low in toluene (0.45 kcal/mol = 157 cm−1). However, the barrier is genuine, because the collective Cl–C4 elongating along with epoxy closing/opening mode in the intermediate and in the product have energies definitely below the barrier.

Based on the B3LYP and MP2/aug-cc-pVDZ calculations, 51 cysteine conformers were found to be stable in the gas phase. The calculations were repeated for the most stable eight structures by using the aug-cc-pVTZ basis set. To estimate the influence of water on the cysteine conformation, the IEF-PCM/B3LYP/aug-cc-pVDZ calculations were carried out and showed 44 neutral and 12 zwitterion conformers to be stable in the water solution. The most stable cysteine structure in water appeared to be the zwitterionic conformer quite similar to the molecule observed in the crystal state.

DFT (B3LYP/6-311++G**, B3PW91/6-311++G**) Gibbs free energy and single point CCSD(T)/6-311++G**//DFT total energy calculations were performed to investigate stability and tautomerism of C5-substituted 1,2,4-triazoles. Three different tautomers are possible for the substituted 1,2,4-triazoles: N1–H, N2–H, and N4–H. Unlike for the 1,2,3-triazoles, where the most stable is the N2–H tautomer regardless of substituent applied, for the 1,2,4-triazoles, the electron donating substituents (–OH, –F, –CN, –NH2, and –Cl) and the C5-cation stablize the N2–H tautomer, whereas the electron withdrawing substituents (–CONH2, –COOH, –CHO, –BH2, and –CFO) and the C5-anion stablize the N1–H tautomer. Except for the C5-anion and C5-cation, the N4–H form is the least stable tautomer. The relative stability of the C5-substituted 1,2,4-triazole tautomers is strongly influenced by attractive and/or repulsive intramolecular interactions between substituent and electron donor or electron acceptor centres of the triazole ring.

Stability of two pyrazole tautomers monosubstituted at C5 position by various substituents was investigated at the MP2/6-311++G** level. For each substituent studied, the energy difference between the two tautomers, expressed in terms of ΔE and ΔG, was calculated. The F and OH substituents, the strongest electron donating groups, stabilize significantly the N2–H tautomer, whereas the CFO, COOH, and BH2, the strongest electron withdrawing groups, favour definitely the N1–H tautomer. As for monosubstituted imidazoles, only the most strongly acting substituents affect significantly the highest occupied π and σ orbitals. The other substituents introduce no noteworthy changes to the electronic structure. The calculated IR spectra form a basis for differentiation the two tautomers in their mixture.

Model chiral β -lactam molecules, (3 S )-and (4 R )-fluoro-2-azetidinone, were calculated at the B3PW91/aug-cc-pVTZ level, to be hydrogen bonded with the achiral HX molecule (X=F, Cl, Br). Two stable structures of the complex are possible: a cyclic or a bent H-bond, in which the HX molecule interacts with the CO group and is either close to NH or CH 2 (CHF) moiety, respectively. The VCD effect of these two forms differs in several respects, however, the main difference is the sign of the VCD rotational strength of the ν (HX) stretching vibrations revealing the geometry of the hydrogen bond complex.

Fourteen [2+2], [2+4], and [4+4]-dicyclopentadiene isomers were calculated by ab initio, DFT, and semiempirical methods. The most stable two isomers appeared to be the exo - and endo -[2+4]-dicyclopentadiene molecules. In contrast to thermal dimerization isomer contents, the former is slightly more stable than the later. The calculated C–C distances were found to be in plausible agreement with the experimental X-ray values. For four isomers, the theoretical B3PW91/aug-cc-pVDZ 1 H NMR and 13 C NMR chemical shifts were calculated and, when possible, compared with the experimental chemical shifts.

The theoretical geometries, rotational constants, VCD, and IR spectra for the chiral ( S )-HXCCCFH (X=F, Cl, Br) allene molecules were calculated at the B3PW91/aug-cc-pVTZ level. We have shown that there is plausible adequacy between IR spectrum of ( S )-1,3-difluoroallene molecule calculated at B3PW91/aug-cc-pVTZ level and experimental spectra of the racemate system. For the other molecules studied, the experimental spectra were not published, yet, although, some results reported earlier for alkilohalogenoallenes are in line with our findings. The halogen influence on the VCD and IR spectra of the studied molecules is discussed.

Total energies of all 32 chiral stereoisomers of 17β-estradiol, the molecule widespread in nature, were calculated at the HF/6-31G∗ level. Despite the fact that the 17β- and 17α-estradiols are natural compounds they appeared not to be the lowest energy isomers. Notably, for each individual chiral isomer, from 6 to 34 conformations with different shapes of the B, C, and D rings were found. However, the conformations can be further grouped into a number of skeleton type classes: for example, 34 conformers of one stereoisomer fell into 10 classes. The plot of potential energy function due to rotation of the 17OH group in 17β-estradiol molecule has also been shown.

DFT (B3PW91/6-31G** and B3PW91/6-311G**) calculations were performed for dibenzylcarbamic acid, either monomer or dimer (DBCAD). Six possible structures of the dimer were considered. Calculated geometrical parameters of the most stable dimer were compared with those published for the dibenzylcarbamic acid dimer crystalline solid. The calculated IR spectrum was used for the assignment of the frequencies observed in the experimental IR spectrum of dimer dibenzylcarbamic acid.

Theoretical Gibbs free energies have been determined for a set of cycloaddition products of allene with CO 2 , CS 2 or OCS molecules, and of CH 2 C X with CH 2 C Y molecule (X, Y=O, S). Each of the cycloaddition reactions leads to one or two isomeric products with four-membered heterocyclic ring. Theoretical thermochemical data suggest that the isomers in which sulphur atom is build into the four-membered ring can be easily formed in different reactions whereas formation of those with oxygen atom in the ring strongly depends on the considered reaction. Analysis of the theoretical 1 H and 13 C chemical shifts forms a basis for the detection of the isomer traces in reaction mixtures as well as for the elucidation of future experimental spectra.

The tautomerism of the histamine molecule was explored based on quantum chemical calculations both in the gaseous state and in aqueous medium. Structural optimizations were performed at the ab initio Hartree-Fock (HF) and the second order Moller-Plesset (MP2) perturbation level. The most stable tautomer in aqueous medium appeared to be the N(3) monocation, with strong intramolecular hydrogen bonding. Results from calculations prove that the previous hypothesis on interaction with the hypothetical H 2 receptor remains valid, even though this hypothesis involved a slightly different assumption regarding the structure of the most stable form. The most stable neutral form in aqueous medium turned out to be the opened N(3) gauche structure.