Protonation of phenylboronic acid: Comparison of G3B3 and G2MP2 methods

G3B3 and G2MP2 calculations using Gaussian 03 have been carried out to investigate the protonation preferences for phenylboronic acid. All nine heavy atoms have been protonated in turn. With both methodologies, the two lowest protonation energies are obtained with the proton located either at the ipso carbon atom or at a hydroxyl oxygen atom. Within the G3B3 formalism, the lowest‐energy configuration by 4.3 kcal · mol^?1 is found when the proton is located at the ipso carbon, rather than at the electronegative oxygen atom. In the resulting structure, the phenyl ring has lost a significant amount of aromaticity. By contrast, calculations with G2MP2 show that protonation at the hydroxyl oxygen atom is favored by 7.7 kcal · mol^?1. Calculations using the polarizable continuum model (PCM) solvent method also give preference to protonation at the oxygen atom when water is used as the solvent. The preference for protonation at the ipso carbon found by the more accurate G3B3 method is unexpected and its implications in Suzuki coupling are discussed. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Comparison of the use of the MNDO and MINDO/3 methods with ab initio methods to study tautomerism in histamine, 2- and 4-methylhistamine

The semiempirical MNDO and MINDO/3 methods are used to study the various tautomeric forms of histamine, 2-methylhistamine, and 4-methylhistamine. Comparisons of the optimized structures and tautomerization energies are made with values obtained from ab initio Hartree-Fock calculations using the 3-21G and STO-3G basis sets. Based on these results and previous comparisons of STO-3G results with x-ray structures, the present results indicate that while there are some differences in the values of the structural parameters, the changes in structure upon tautomerization and/or protonation are very similar. Further analysis of the MNDO and MINDO/3 structures by means of their utilization in 3-21G and STO-3G calculations indicates that either of these semiempirical methods provides reliable values for the structural parameters. Both methods give good qualitative agreement with the ab initio calculations for the relative energies of the various tautomers in the three compounds. In these studies the MNDO method appears to give better quantitative agreement with the 3-21G and STO-3G results than the MINDO/3 method.     

A conformational analysis of the six isomers of thiobispyridine

The conformational behaviour of the six isomers of thiobispyridine has been investigated using ab initio STO-3G*//rigid-roto, STO-3G*//STO-3G* and 6–31G**//STO-3G* molecular orbital models. The analysis reveals both the importance of optimising critical structure parameters and the basis set dependence of calculated rotational barrier heights. The most reliable model (6–31G**//STO-3G*) clearly indicates that the minimum energy conformers are not planar and that energy barriers between 30–100 kJ mol^?1 restrict inter-conversion to planar structures, thereby preventing conjugation between the p-electrons of the sulfur atom and the π system of both pyridine rings. From the calculated barrier heights, two mechanisms can be employed to explain conformer interconversion about the C? S bond: a disrotatory one-ring flip or a conrotatory two-ring flip mechanism. Where comparisons can be made (eg. 2,2′-thiobispyridine), dipole moment calculations are shown to be in good agreement with experiment. Finally, of the six isomers, appropriately substituted 2,2′, 2,3′- and 2,4′-thiobispyridines are most prone to a Smiles rearrangment.     

An abinitio study of protonation and alkylation of aminopyridine

STO-3G abinitio calculations show that the first site of protonation in 2-, 3- and 4-aminopyridines is the cyclic nitrogen, whatever the position of the amino group. There is an excellent linear relationship between the calculated proton affinities and the experimental pK_a values (r = 0.995). The protonation site is also confirmed by π→π* transition energy variations as a function of position of the amino-group due to protonation; these effects are connected with the MO structures. Basicity and reactivity in alkylation reveal lone pair localization.     

Nonempirical approach to the conformational analysis of 2,4-dimethyl-1,3,2-dioxaborinane and its oxonium ions

Using nonempirical quantum-chemical approximations RHF//STO-3G, 3-21G, 6-31G(d) and MP2//6-31G(d,p) a conformation isomerism of 2,4-dimethyl-1,3,2-dioxaborinane and its oxonium ions was studied. It was shown that the potential energy surface of the studied molecules has minima corresponding to equatorial (main minimum) and axial sofa forms and maxima corresponding to equatorial and axial conformations of 2,5-twist forms. Calculated values of the barriers of internal rotation of methyl group at the ring C⁴ atom were found. It was also established that the heat of protonation of the cyclic boric ester was smaller than of the non-boric analog, cis-2,4-dimethyl-1,3-dioxane, owing to decrease in basicity of the oxygen atoms in the cyclic boric ester due to partial double bond character of B-O bond.     

Dependence of the reactivity of five-membered aromatic heterocycles on their structure. 5. Protonation of furazane,furoxane, and their aminoderivatives

Proton affinity of furazane, furoxane, and their aminoderivatives for protonation at various centers was calculated by ab initio methods using the STO-3G basis set. Basicity was found to decrease in the following order: N-oxide oxygen atom, endocyclic nitrogen atom, amino group. The presence in the ring of aminogroups or N-oxide functions leads to elevated proton affinity of the basic centers which are located in the active positions of the ring.For Communication 4, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1261–1264, September, 1989.     

A theoretical study on the protonation of benzamide

We have performed an ab initio study of the protonation of benzamide, using a STO-3G minimal basis set. According to our results, benzamide is an oxygen-base in the gas-phase. Rotation of the -CONH₂ group respect to the aromatic ring does not affect the basicity of the molecule. If the presence of the solvent causes pyrimidization of the -NH₂ group, the intrinsic basicity of the O atom decreases, while that of the N atom increases and the interaction of this center with the solvent is stronger, favoring nitrogen protonation in solution.     

Basicity of azoles. VII. Basicity of C-aminopyrazoles in relation to tautomeric and protonation studies

The pK_a values of five aminopyrazoles [3(5)-amino, 1-methyl-3-amino, 1-methyl-5-amino, 4-amino and 1-methyl-4-amino] were determined. The aqueous basicities are discussed in terms of tautomerism (72% of 3-amino tautomer), protonation site (only 4-aminopyrazoles protonate on the amino group) and amino substituent effects. The results of theoretical calculations, carried out at the semiempirical INDO level, indicate that in the gas phase 3- and 5-aminopyrazoles protonate on the pyrazolic nitrogen atom, whereas 4-aminopyrazoles possess similar proton affinities for both nitrogen atoms (pyrazolic and amino).     

Gas-phase protonation of unsaturated ethers: Experimental and theoretical study of 2,3-and 2,5-dihydrofuran and related compounds

The protonation of 2,3- and 2,5-dihydrofuran is examined in gas-phase equilibrium proton transfer reactions conducted in an ion cyclotron resonance spectrometer. The thermodynamically favoured site of protonation in the two compounds is seen to be different: whereas the first isomer forms a carbocation upon protonation, the second isomer protonates on the oxygen atom to form an oxonium ion. The results obtained with substituted derivatives and with linear analogues confirm these conclusions. Molecular orbital calculations on the various structures for protonated bases are performed at the 4–31G level with correction for configuration interaction effects and at the 4–31G* level. The latter basis set provides the best results owing to the introduction of d-type orbitals on the oxygen atom. The calculation results substantiate the experimental observations and provide details on the molecular structure of the protonated species.     

Proton migration and tautomerism in protonated triglycine.

Proton migration in protonated glycylglycylglycine (GGG) has been investigated by using density functional theory at the B3LYP/6-31++G(d,p) level of theory. On the protonated GGG energy hypersurface 19 critical points have been characterized, 11 as minima and 8 as first-order saddle points. Transition state structures for interconversion between eight of these minima are reported, starting from a structure in which there is protonation at the amino nitrogen of the N-terminal glycyl residue following the migration of the proton until there is fragmentation into protonated 2-aminomethyl-5-oxazolone (the b(2) ion) and glycine. Individual free energy barriers are small, ranging from 4.3 to 18.1 kcal mol(-)(1). The most favorable site of protonation on GGG is the carbonyl oxygen of the N-terminal residue. This isomer is stabilized by a hydrogen bond of the type O-H.N with the N-terminal nitrogen atom, resulting in a compact five-membered ring. Another oxygen-protonated isomer with hydrogen bonding of the type O-H.O, resulting in a seven-membered ring, is only 0.1 kcal mol(-)(1) higher in free energy. Protonation on the N-terminal nitrogen atom produces an isomer that is about 1 kcal mol(-)(1) higher in free energy than isomers resulting from protonation on the carbonyl oxygen of the N-terminal residue. The calculated energy barrier to generate the b(2) ion from protonated GGG is 32.5 kcal mol(-)(1) via TS(6-->7). The calculated basicity and proton affinity of GGG from our results are 216.3 and 223.8 kcal mol(-)(1), respectively. These values are 3-4 kcal mol(-)(1) lower than those from previous calculations and are in excellent agreement with recently revised experimental values.     

Protonation States of Glufosinate in Aqueous Solution

Glufosinate, an analogue of glutamic acid (also known as phosphinothricin), is an important herbicide. The protonation constants of glufosinate were determined by means of potentiometric titrations at variable temperatures with ionic strength 0.5 mol·L^?1 (NaCl solution). The heat effects of the protonation reactions of glufosinate were measured by direct calorimetry. NMR spectroscopies have demonstrated that the first protonation site occurs on the nitrogen atom in the amino group, followed by one of the oxygen atoms in the phosphono group, and finally the carboxyl oxygen atom. This trend is in good agreement with the enthalpy of protonation and crystal structure results. These data will help to predict the speciation of glufosinate in physiological systems.     

Protonation and deprotonation of hydroxamic acids. An MO ab initio study

Ab initio molecular orbital calculations with 4-31G//4-31G, 6-31G^*//4-31G and 6-31+G//4-31G basis sets have been used to examine the structure, relative energy, protonation and deprotonation of a series of seven hydroxamic acids in the gas phase. The results show that hydroxamic acids are predominantly in the E-TS form and that the most probable protonation site is the carbonyl oxygen atom, while deprotonation proceeds by loss of NH hydrogen.     

A theoretical study of the protonation of methylindole derivatives

Ab initio calculations on indole and all its mono-substituted methyl derivatives, using an STO-3G minimal basis set, show that the most basic site is C3. Protonation at the nitrogen atom cannot compete with protonation at C3; and C2 is the less basic site in all cases. The basicity increases with methyl substitution, with the only exception of 3-methyl indole. A good linear correlation exists between calculated and corresponding thermodynamics pK values. 2-Aminoindole is a much stronger base than methylindoles and its high pK value can be explained by the strong interactions with the solvent through tautomeric forms which accumulate positive charge at the NH₂ group. Intramolecular quenching of the fluorescence of some indole derivatives involves intramolecular proton transfer to C4 rather than C2. Reasons why ring nitrogens can behave as either π-acceptors or π-donors in this series are discussed.     

Theoretical study of the changes in the electronic structure of benzonitrile accompanying its conversion into a radical anion

The electronic structure of benzonitrile and its radical anion have been investigated at different levels of ab initio MO theory: STO-3G, 6-31G and 6-31G^**. The changes in the electronic structure of the neutral molecule accompanying its conversion into the corresponding radical anion have been estimated. It was established that the radicalization leads to significant changes in the bond lengths with double and triple bond character expressed in the conjugated system. The distribution of the total atomic charges on transition from the neutral molecule to the corresponding radical anion have been investigated using the Mulliken population analysis. The distribution of the odd electron density in the radical anion was estimated at the different basis sets: STO-3G, 6-31G and 6-31G^**. The ab initio calculations suggest that the quinoid structure is preferred for the radical anion.     

Proton magnetic resonance studies of tautomerism in substituted pyrimidines

Studies of line width and chemical shift vs. temperature for amide and hydroxyl proton magnetic resonance signals from: barbituric acid, dialuric acid, parabanic acid, alloxan and alloxan monohydrate dissolved in anhydrous dimethyl sulfoxide-d₆ are reported. The behavior of the amide signals shows that, between 20 and 65°C, none of the compounds listed exhibits lactim-lactam tautomerism. The amide proton resonance in uracil has also been investigated. The signal is a closely spaced, equal intensity, doublet due to the non-equivalence of H(1) and H(3). Again, no evidence of tautomerism is observed. Activation energies for the hydroxyl resonances in dialuric acid and alloxan monohydrate indicate hydrogen bonding between solute and solvent. The results of simple LCAO-MO calculations are in accord with the experimental conclusions concerning tautomeric equilibria.     

Proton and sodium ion affinities of glycine and its sodium salt in the gas phase. Ab initio calculations

The energies of protonation and Na⁺ cationization of glycine (GLY) and its (GLY ? H + Na) salt in the gas phase were calculated using ab inltio calculations. The proton affinity of GLY, valued at the MP2/6–31G*//3-21G level, is 937 kJ mol^?1. The amino function is confirmed to be the most favourable site of protonation: ‘proton affinities’ of the carbonyl and hydroxyl functions are calculated to be 75 and 180 kJ mol^?1, respectively, lower than that of NH₂ at the MP2/6-31G*//3–21G level. Calculations performed up to the MP2/6–31G*//3–21G level give the Na⁺ affinity of GLY as 189 kJ mol^?1 and the H⁺ and Na⁺ affinities of (GLY – H + Na) as 1079 and 298 kJ mol^?1, respectively. The geometries of all neutral and protonated species optimized with the 3–21G basis set are described. Both H* and Na⁺ cations complex preferably between the nitrogen atom and the carbonyl oxygen atom, leading to pseudo-five-membered ring structures in which Na? O and Na? N bonds lengths are greater than 2 Å.     

Proton affinity of β-oxalylaminoalanine (BOAA): Incorporation of direct entropy correction into the single-reference kinetic method

A new version of the single-reference-extended kinetic method is presented in which direct entropy correction is incorporated. Results of calibration experiments with the monodentate base pyridine and the bidentate base ethylenediamine are presented for which the method provides proton affinities in excellent agreement with published values and reasonable predictions for the protonation entropies. The method is then used to determine the proton affinity and protonation entropy of the non-protein amino acid beta-oxalylaminoalanine (BOAA). The PA of BOAA is found to be 933.1 +/- 7.8 kJ/mol and a prediction for the protonation entropy of -39 J mol(-1) K(-1) is also obtained, indicating a significant degree of intramolecular hydrogen bonding in the protonated form. These results are supported by hybrid density functional theory calculations at the B3LYP/6-311++G**//B3LYP/6-31+G* level. They indicate that the preferred site of protonation is the alpha-nitrogen atom (PA = 935.0 kJ/mol) and that protonated BOAA has a strong hydrogen bond between the hydrogen on the alpha-amino group and one of the carbonyl oxygen atoms on the side chain.     

The effects of oxidation and protonation on the N-glycosidic bond stability of 8-oxo-2′-deoxyguanosine: DFT study

This work is an attempt to evaluate the ability of protonation of 8-oxo-2′-deoxyguanosine (8-oxodG) and the effects of oxidation and protonation on its N-glycosidic bond stability by using the density functional theory B3LYP/6-31++G(d, p) method. In all modified forms, the length of the N9–C1′ bond increases as compared to the neutral system 8-oxodG. Especially, the changes are much more obvious for the di-cationic systems. The analysis for the ability of protonation indicates that for the mono-protonated systems, the O8 atom becomes the preferred protonation site in the gas phase. From the dissociation energies of the N-glycosidic bond, it has been found that the homolytic cleavage becomes more difficult upon introducing positive charge in the base ring. In contrast, these systems favor significantly the heterolytic cleavage, especially for the di-cationic systems in which the dissociation energy values are negative. The influence is most prominent with the mono-cation obtained by O8 protonation.     

X-ray structural and13C NMR spectroscopic investigation of 4,7-diaminocoumarins

An x-ray structural study has been made of 7-diethylaminocoumarin and 4-morpholino-7-diethylaminocoumarin. A study has been made of the¹³C NMR spectra of these compounds and other 4,7-diaminocoumarins, in CDCl₃, and in acidic media. These studies have established that the site of first protonation is the nitrogen atom in position 7, and the site of the second protonation is the lactone oxygen atom. It is concluded that the 4-amino group is effectively conjugated with the carbonyl group in 4,7-diaminocoumarins.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 802–810, April, 1991.     

Diazanaphthalenes: A 13C NMR investigation on the site of protonation and pKa values

The pH dependence of the ¹³C chemical shifts (δ) of the diazanaphthalenes has been recorded. From this dependence the pK_a values have been determined using the Henderson-Hasselbach equation. The change in ¹³C chemical shifts under the influence of nitrogen protonation (Δδ) has been predicted using the Δδ values of quinoline and isoquinoline. The correlation between observed and expected Δδ values of the symmetric diazanaphthalenes is very good. Assuming these changes in chemical shifts to be of general validity, the site of protonation in the asymmetric diazanaphthalenes has been determined by comparison of the expected Δδ values for α- and β-nitrogen protonation with the observed ones. The site of protonation for 1,6- and 1,7-naphthyridine is the β-nitrogen atom, whereas for cinnoline both monoprotonated species are present in a significant amount.