Ewa D. Raczyńska

On the Harmonic Oscillator Model of Electron Delocalization (HOMED) Index and its Application to Heteroatomic π-Electron Systems

The HOMA (Harmonic Oscillator Model of Aromaticity) index, reformulated in 1993, has been very often applied to describe π-electron delocalization for mono- and polycyclic π-electron systems. However, different measures of π-electron delocalization were employed for the CC, CX, and XY bonds, and this index seems to be inappropriate for compounds containing heteroatoms. In order to describe properly various resonance effects (σ-π hyperconjugation, n-π conjugation, π-π conjugation, and aromaticity) possible for heteroatomic π-electron systems, some modifications, based on the original HOMA idea, were proposed and tested for simple DFT structures containing C, N, and O atoms. An abbreviation HOMED was used for the modified index.

Quantum-chemical studies on the favored and rare tautomers of neutral and redox adenine.

All possible twenty-three prototropic tautomers of neutral and redox adenine (nine amine and fourteen imine forms, including geometric isomerism of the exo ═NH group) were examined in vacuo {DFT(B3LYP)/6-311+G(d,p)}. The NH → NH conversions as well as those usually omitted, NH → CH and CH → CH, were considered. An interesting change of the tautomeric preference occurs when proceeding from neutral to reduced adenine. One-electron reduction favors the nonaromatic amine C8H-N10H tautomer. This tautomeric preference is similar to that (C2H) for reduced imidazole. Water molecules (PCM model) seem to not change this trend. They influence solely the relative energies. The DFT vertical detachment energy in the gas phase is positive for each tautomer, e.g., 0.03 eV for N9H-N10H and 1.84 eV for C8H-N10H. The DFT adiabatic electron affinity for the favored process, neutral N9H-N10H → reduced C8H-N10H (ground states), is equal to 0.18 eV at 0 K (ZPE included). One-electron oxidation does not change the tautomeric preference in the gas phase. The aromatic amine N9H-N10H tautomer is favored for the oxidized molecule similarly as for the neutral one. The DFT adiabatic ionization potential for the favored process, neutral N9H-N10H → oxidized N9H-N10H (ground states), is equal to 8.12 eV at 0 K (ZPE included). Water molecules (PCM model) seem to influence solely the composition of the tautomeric mixture and the relative energies. They change the energies of the oxidation and reduction processes by ca. 2 eV.

Amidines. Part 13. Influence of substitution at imino nitrogen atom on pKa values of N1N1-Dimethylacetamidines

20 N1N1-Dimethylacetamidines containing alkyl, aralkyl, or substituted phenyl groups have been synthesized, and their pKa values in 95.6% ethanol (azeotrope) measured. The pKa values obtained were correlated with Hammett σ constants. The appliciability of various σ values is discussed, and it is shown that for substituents at nitrogen σ° values should be used. It has also been shown that the pKa values of amidines correlate well with the pKa values of corresponding primary amines, and that this correlation can serve for the prediction of the pKa of amidine. Comparison of the correlations for N1N1-dimethylacetamidines with those for N1N1-dimethylformamidines indicate that sensitivity of the amidine group to substitution at the imino nitrogen atom depends to a considerable degree on substitution at a functional carbon atom.

Dipole moments of amidines and electron distribution within their functional group

Abstract Two series of N,N,N ′-trisubstituted amidines were prepared, their dipole moments measured in benzene solution, and their E configuration determined from the nuclear Overhauser effect. When the configuration is established, the dipole moments can be analyzed with respect to their direction, exploiting the substituents in the para position. The vector difference between the actual dipole moment and that calculated for the classical structural formula is called the mesomeric dipole moment and serves as a measure of the n -π conjugation within the amidine group. Compared to amides and thioamides this conjugation is weaker and is also strongly affected by the substituents on nitrogen. Additional proof of the conjugation was obtained from a search in the Cambridge Structural Database which revealed a lengthened CN bond, shortened CN bond, and a significant correlation between the two bond lengths.

Geometric and energetic consequences of prototropy for adenine and its structural models – a review

Heterocycles containing one or more amidine moieties {–NH–C(R) N–} such as adenine and its building blocks, imidazole, 4-aminopyrimidine, and purine, are excellent examples of tautomeric systems for which changes of position(s) of labile proton(s) cause parallel changes of geometric and energetic parameters for prototropic tautomers. One-electron oxidation has a slight effect on this relationship. The amino-imine conversions within the amidine group(s) are favored. Well delocalized (aromatic) tautomers, containing labile proton(s) at heteroatom(s), are major, minor, or rare forms. Non-aromatic tautomers with a labile proton at the C atom can be considered as very rare isomers. Dramatic changes take place for reduced heterocycles. Electron delocalization is not the main factor that dictates tautomeric preferences. The HOMED/ΔE relationship seems to be more complex. The enamino-imine conversions predominate and some very rare forms have the lowest energies. This clearly shows the importance of very rare tautomers, often neglected in proton-transfer, electron-transfer, and ion–radical reactions.

Application of semiempirical method (AM1) to the study of tautomeric equilibria in the gas phase for simple compounds containing the amidine group: 4(5)-substituted imidazoles

Abstract Semiempirical method (AM1) has been used to predict the tautomeric equilibrium constants (pKT) in the gas phase for 4(5)-substituted imidazoles. The pKT values have been calculated on the basis of heats of formation of individual tautomers. In calculations it has been assumed that the TΔS term has the same value for both tautomers. For comparison, the pKT values have also been estimated on the basis of the calculated (by AM1) proton affinities of N-methyl-4- and 5-substituted imidazoles. Both estimations give almost the same pKT values. Obtained results are compared with those found in solution. Comparison shows that the gas-phase substituent effects do not reproduce well those in solution. To find an explanation of this observation, the influence of rotational isomerism of substituent on the tautomeric equilibrium constant has been studied. Proton affinities and deprotonation enthalpies of 4- and 5-substituted imidazoles have also been calculated. For unsubstituted imidazole, 4(5)-methyl-imidazole and their N-methyl derivatives they are compared with those experimentally obtained. Errors are considerably smaller than the average errors of AM1 method for nitrogen acids and bases.

Tautomeric and conformational preferences in nitraminopyridines: Comparison of theoretical and experimental data

Abstract AM1 calculations show 2-nitraminopyridine to contai 97.7% of 1,2-dihydro-2-nitrimino-pyridine form which was found to be the most stable in the gas phase. Except the proton transfer processes, dimerization was also found to appear in this compound. Instead, non-planar nitramine form was found to dominate for 4-nitraminopyridine. The results are related to experimental (X-ray and 15N NMR) data.

Consequence of one-electron oxidation and one-electron reduction for aniline

Quantum-chemical calculations were performed for all possible isomers of neutral aniline and its redox forms, and intramolecular proton-transfer (prototropy) accompanied by π-electron delocalization was analyzed. One-electron oxidation (PhNH2 – e → [PhNH2]+•) has no important effect on tautomeric preferences. The enamine tautomer is preferred for oxidized aniline similarly as for the neutral molecule. Dramatical changes take place when proceeding from neutral to reduced aniline. One-electron reduction (PhNH2 + e → [PhNH2]-•) favors the imine tautomer. Independently on the state of oxidation, π- and n-electrons are more delocalized for the enamine than imine tautomers. The change of the tautomeric preferences for reduced aniline may partially explain the origin of the CH tautomers for reduced nucleobases (cytosine, adenine, and guanine).

FT-IR spectroscopic, AM1 and PM3 computational studies of conformation of natural products: cytisine☆

Infrared spectra were recorded for cytisine (1) and its model compounds: N-methyl-2-pyridone (2) and piperidine (3) in solution. Eight solvents of different polarity, polarizability and acid-base properties: CCl(4), CS(2), CHCl(3), CDCl(3) (for comparison with the NMR spectra), CH(2)Cl(2), MeOH, Et(2)O and Et(3)N were chosen. Experimental FT-IR spectra were analysed with the help of those calculated for isolated derivatives at the AM1 and PM3 levels. Influence of environment on the conformational preferences in solvated cytisine was discussed and compared with those in the solid state (X-ray measurements) and in the gas phase (quantum-mechanical calculations).

Application of infrared spectrometry to the study of tautomeric equilibria and hydrogen bonding basicity of medical and biochemical agents: N,N′-disubstituted amidines

The hydrogen bonding basicity of 20 N,N′-disubstituted formamidines, acetamidines and benzamidines containing the same or different groups at the amino and imino nitrogen atoms was measured by means of the formation constant KHB of their complexes with 4-fluorophenol in carbon tetrachloride. A method for the prediction of tautomeric equilibrium constants is proposed and was applied to unsymmetrically N,N′-disubstituted amidines. The results obtained were compared with those found on the basis of pKa measurements in azeotropic ethanol.