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This work extends our earlier quantum chemical studies on the gas-phase basicity of very strong N-bases to two series of nitriles containing the methylenecyclopropene and cyclopropenimine scaffolds with dissymmetrical substitution by one or two electron-donating substituents such as Me, NR2, N=C (NR2)2, and N=P (NR2)3, the last three being strong donors. For a proper prediction of their gas-phase base properties, all potential isomeric phenomena and reasonable potential protonation sites are considered to avoid possible inconsistencies when evaluating the energetic parameters and associated protonation or deprotonation equilibria B + H+ = BH+. More than 250 new isomeric structures for neutral and protonated forms are analyzed. The stable structures are selected and the favored ones identified. The microscopic (kinetic) gas-phase basicity parameters (PA and GB) corresponding to N sites (cyano and imino in the cyclopropenimine or in the substituents) in each isomer are calculated. The macroscopic (thermodynamic) PAs and GBs, referring to the isomeric mixtures of favored isomers, are also estimated. The total (pushing) substituent effects are analyzed for monosubstituted and disubstituted derivatives containing two identical or two different substituents. Electron delocalization is examined in the two π–π conjugated transmitters, the methylenecyclopropene and cyclopropenimine scaffolds. The aromatic character of the three-membered ring is also discussed. [ABSTRACT FROM AUTHOR]

Quantum chemical calculations were carried out for deprotonated (P−) and protonated purine (PH+) and for adducts with one alkali metal cation (P−M+ and PM+, where M+ is Li+ or Na+) in the gas phase {B3LYP/6-311+G(d,p)}, a model of perfectly apolar environment, and for selected structures in aqueous solution {PCM(water)//B3LYP/6-311+G(d,p)}, a reference polar medium for biological studies. All potential isomers of purine derivatives were considered, the favored structures indicated, and the preferred sites for protonation/deprotonation and cationization reactions determined. Proton and metal cation basicities of purine in the gas phase were discussed and compared with those of imidazole and pyrimidine. Bond-length alternations in the P, PH+, P−M+, and PM+ forms were quantitatively measured using the harmonic oscillator model of electron delocalization (HOMED) indices and compared with those for P. Variations of the HOMED values when proceeding from the purine structural building blocks, pyrimidine and imidazole, to the bicyclic purine system were also examined. Generally, the isolated NH isomers exhibit a strongly delocalized π-system (HOMED > 0.8). Deprotonation slightly increases the HOMED values, whereas protonation and cationization change the HOMED indices in different way. For bidentate M+-adducts, the HOMED values are larger than 0.9 like for the largely delocalized P−. The HOMED values correlate well in a comprehensive relationship with the relative Gibbs energies (ΔG) calculated for individual isomers whatever the purine form is, neutral, protonated, or cationized. When PCM-DFT model was utilized for P−, PH+, PM+, and P−M+ (M+ = Li+) both electron delocalization and relative stability are different from those for the molecules in vacuo. The solvation effects cause a slight increase in HOMEDs, whereas the ΔEs decrease, but in different ways. Hence, contribution of particular isomers in the isomeric mixtures of PH+, PM+, and P−M+ also varies. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • HOMEDs calculated for isomers with PCM are almost parallel to those in vacuo. • Electron delocalization in iC − isomers varies in analogous way as in C − and U − isomers. • Mechanism of one-electron gain seems to be similar for isomers of pyrimidine bases. • Lack of analogy in bond length alternation exists between iC + , C + , and U + isomers. • Mechanism of one-electron loss can be different for isomers of pyrimidine bases. Abstract For favored and rare prototropic tautomers of isocytosine (iC), geometric consequences of ionization, one-electron loss (iC − e → iC+) and one-electron gain (iC + e → iC−), have been studied. Effects of protonation and deprotonation on geometry of neutral isocytosine (iC + H+ → iCH+ and iC − H+ → iC − H−) as well as of its charged radicals (iC− + H+ → iCH and (iC+ − H+ → iC − H ) have also been examined for selected isomers. Bond length alternation for the ground states of individual isomers, investigated in two extreme environments at the B3LYP/6-311+G(d,p) and PCM(water)//B3LYP/6-311+G(d,p) levels, have been quantitatively described using the geometry-based HOMED (harmonic oscillator model of electron delocalization) index. Generally, one-electron loss, one-electron gain, and proton-transfer reactions change electron delocalization in isocytosine isomers, and consequently the HOMED values. However, the HOMED indices calculated for structures optimized at the DFT level vary analogously to those optimized with PCM. When compared to other pyrimidine bases, cytosine (C) and uracil (U), exhibiting analogous tautomeric equilibria, rotational and/or geometric isomerism of exo groups (NH 2 / NH and/or OH/ O), linear trends can be distinguished between the HOMED values of negatively ionized isomers (iC−, C−, and U−). For positively ionized isomers (iC+, C+, and U+), relations between the HOMED indices seem to be more complex. This indicates some similarities in mechanisms of one-electron gain and some differences in mechanisms of one-electron loss for isomers of pyrimidine bases. Hence, the HOMED descriptor can be considered as some kind of 'marker index' for ionization mechanism in analogous series of tautomeric π-electron systems. [ABSTRACT FROM AUTHOR]

Abstract: The HF, MP2, and DFT structures of neutral (N6) and monoprotonated (N6H+) hexazine, nitrogen analogues of benzene, were discussed. For neutral N6, the extended geometry-based HOMED (harmonic oscillator model of electron delocalization) index, being a measure of π-electron delocalization, is close to that of benzene. Protonation of one N atom in planar N6 has no important effect on the HOMED value. Contrary to benzene, planar N6H+ does not lose its aromatic character. π-Electrons of the ring are not engaged in the formation of the NH bond. The proton affinity (PA) of N6 seems to be considerably lower than that of benzene (by ca. 16kcalmol−1 at the G2 level), indicating great Nirs repulsion and electron-withdrawing effects of the N-aza groups (ca. 12kcalmol−1 for each N atom). [ABSTRACT FROM AUTHOR]

The gas-phase basicity (GB) of the flexible polyfunctional N¹,N¹-dimethyl-N²-β-(2-pyridylethyl)formamidine (1) containing two potential basic sites (the ring N-aza and the chain N-imino) is obtained from proton-transfer equilibrium constant measurements, using Fourier-transform ion-cyclotron resonance mass spectrometry. Comparison of the experimental GB obtained for 1 with those reported for model amidines and azines indicates that the chain N-imino in the amidine group is the favored site of protonation. Semiempirical (AM1) and ab initio calculations (HF, MP2, and DFT), performed for I and its protonated forms, confirm this interpretation. These results are in contrast to those found previously for N¹,N¹-dimethyl-N²-azinylformamidines (containing the amidine function directly linked to the azinyl ring), in which the ring N-aza is the most basic site in the gas phase. The separation of the two potential basic sites in I by the ethylene chain interrupts the resonance conjugation between the two functions and changes their relative basicities and, thus, the preferable site of protonation. It also increases the chelation effect against the proton and the gas-phase basicity of 1 in such a magnitude that consequently I may be classified as a superbase (GB = 241.1 kcal mol-1). A transition state corresponding to the internal transfer of the proton (ITP) between the ring N-aza and the chain N-imino in 1 is investigated at the DFT(B3LYP)/ 6-31G** level. The energy barrier calculated for the ITP between the two basic sites is small and vanishes when zero-point vibrational terms and thermal corrections are applied to obtain the enthalpy or Gibbs energy of activation for the proton transfer. Additional calculations at the DFT(MPWIK)/6-31G** level confirm this behavior. This indicates that the quantum-chemical ITP in 1 has a single-well character. The proton is located on the N-imino site, and the H-bond is formed with the N-aza site. [ABSTRACT FROM AUTHOR]

• Neutral caffeine is less aromatic than purine and adenine. • Ionization decreases HOMEDs of caffeine in higher degree than proton-transfer. • Lithiation and H-bonding very little affect aromaticity of caffeine. • Favored acid-base reaction site in caffeine depends on acid-base reagent. • Caffeine is stronger CH-acid than pyrimidine and weaker N -base than imidazole. Effects of positive and negative ionization, deprotonation and protonation, cationization with the simplest metal cation (Li+), and hydrogen-bond formation with the simplest acid (HF) on bond lengths alternation have been studied for the psychoactive stimulant caffeine by quantum-chemical methods. For investigations, the recently extended geometry-based HOMED (harmonic oscillator model of electron delocalization) descriptor has been applied to n-π and π-π conjugated monocyclic and bicyclic fragments of caffeine. This structural index quantitatively describes variations of electron delocalization when proceeding from neutral to ionized, deprotonated, protonated, cationized, and H-bonded forms. Ionization directly affects the number of electrons delocalized in caffeine and cause the greatest HOMED variations. Deprotonation and protonation of caffeine moderately change the bond lengths alternation. Noncovalent interactions, in particular cationization, only slightly influence caffeine-aromaticity. Investigations on protonation, cationization, and H-bonding of caffeine show additionally that the favored basicity site is not always the same in this polyfunctional alkaloid. [ABSTRACT FROM AUTHOR]

Abstract Pyrazine‑2‑amidoxime (PAOX) is a prototypical sp2-hybridized amidoxime. Although, we described first time in details PAOX structure in solid state, the profile of PAOX behavior in aqueous solution still needs to be improved. While, acid-base properties of PAOX have been tried to define just once, the presented description was not complete and based only on the results of potentiometry during complexometric studies. The selection of method gives rise problems to observation the protonation or deprotonation processes of compound studied. Due to above, the presented studies show first time the complete description of PAOX acid-base properties by obtaining its pKa, solubility, partition (P) and distribution (D) coefficients using various methods. Among them, experiments: potentiometry; UV spectrophotometry by using Hammett's function and pH-metric titrations; cyclic voltammetry (CV) with glassy carbon electrode (GCE) and with GCE electropolymerized by poly‑ l ‑glycine (PGGCE); 1H NMR and theoretical calculations (DFT). Generally, combined four types of experimental and theoretical methods were used to estimate PAOX macro acidic-dissociation constants values. Moreover, log P and log D were determined spectrophotometrically and calculated also by DFT methods. No previous reports were found in the presented form regarding the complete drug-like properties, including negative together with positive values of pKa. Additionally, we proved by our electrochemical results that the quantitative analysis of PAOX do not need the special conditions of the electrode used in research. Hence, the comparison of our results to those described in the literature about analysis made for others, amidoxime derivatives. Graphical abstract Unlabelled Image Highlights • The biochemical profile of pyrazine‑2‑amidoxime was obtained by multi-methods. • Drug-like properties of amidoxime derivative were described in details. • Preferred protonation and deprotonation sites in molecule studied were established. • Pyrazine‑2‑amidoxime ionization states were confirmed and discussed. [ABSTRACT FROM AUTHOR]