A semiempirical SCF-MO study of the tautomeric forms of 3-acetyl tetronic- and tetramic acids

Summary A number of tautomeric geometries of 3-acetyl tetramic acid and 3-acetyl tetronic acid were examined using the AM1 and PM3 methods. The results are compared with experimental data and with studies using MNDO and older methods, with the conclusion that both AM1 and PM3 provide satisfactory models of the behaviour of these species.     

Tautomerism of rhodanine

Semiempirical (MINDO/3, AM1, PM3, MNDO) and ab initio (4-31G and 4-3IG + dAO/S basis sets) calculations on the relative stabilities and structures of the five potential tautomeric forms of rhodanine are reported. It is shown that all methods (excepting PM3) predict as most stable 2-thioxo-4-thiazolidinone. These results correspond to the known experimental data. The infrared spectrum of rhodanine was recorded for the region 4000-150 cm^–1, and the characteristic bands were compared with AM1 and 4-31G + dAO/S calculated frequencies. The transition states between five pairs of all possible tautomeric forms of the rhodanine were found by the AM1 method.     

Quantum chemical investigation of the molecular structure of some 2,3-dihydro-1,4-diazepines and related molecules

Accurate ab-initio and semi-empirical molecular orbital calculations with full geometry optimization were performed on the various tautomeric forms of some 2,3-dihydro-1,4-diazepines and related molecules. The highly accurate ab-initio calculations at the HF/6–31G7 level with Möller-Plesset Second-Order Perturbation Theory (MP2) refinement clearly established the higher stability of the enamine tautomer of the 1,4-diazepine ring over the di-imine form by 27.786 kJ/mol, whereas the semi-empirical calculations at the NDDO level (AM1 and PM3) predicted comparable energies within reported errors of the two methods. However, both ab-initio and semi-empirical NDDO methods predicted similar geometries in agreement with observed geometrical parameters. The AM1 calculations predicted small energy differences among the three tautomeric forms of 2,3-dihydro-5-methyl 7-phenyl 1,4-diazepine with the more polar enamine tautomer being the more stable tautomer in the half-chair conformation which is likely to predominate in polar media through stabilizing intermolecular solute-solvent interactions.     

Quantum chemical studies on the tautomerism of some potentially tautomeric aminoindazole derivatives

The aqueous phase AM1, PM3, and PM5 calculation data had indicated that when a potentially tautomeric amino group is placed at 3C position of the indazole ring the ring-chain tautomerism becomes feasible. However, when the amino group is placed at 4–7C of the indazole ring only the annular tautomerism was found to be feasible and no effect of amino group to provoke a ring chain tautomerism was observed. On the other hand amino form of 3 amino substituted indazole was found to be predominant over imino forms whereas for the 4–7 amino substituted indazoles imino forms were found to be predominant over amino forms. The attempt to apply soft–hard base and soft nucleophile–electrophile criteria to protonation and tautomerism phenomena was successful.     

Investigation of the structure and properties of the potentially tautomeric 5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazines in the gas and aqueous phases using the AM1 and PM3/COSMO solvation method

The potentially tautomeric 5,7-dimethyl-6H-pyrrolo[3,4-d]pyidazines, 2H and 6H, and their fixed tautomeric forms were studied in order to predict the most stable form by the restricted Hartree-Foch approach using semiempirical PM3 and AM1 quantum chemical calculations at the SCF level in the gas and aqueous phases. Both methods predicted that the 6H form, 5, is more stable than the other forms, 1-4, in both gas and aqueous phases. The results obtained were found to be in agreement with the experimental data. Monoprotonated forms of 5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazines were also examined. Proton affinity calculations predicted that the first protonations take place on the N6 atom in the 2H form and on the N2 atom in the 6H form, resulting in a common cation 13.     

Comparative Study of the Structure of Rhodanine, Isorhodanine, Thiazolidine-2,4-dione, and Thiorhodanine

Ab initio (HF and MP2 level) and semiempirical (AM1, PM3, MNDO) calculations on the relative stabilities and structures of the potential tautomeric forms of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine are reported. Ab initio calculations predict that the thiooxo, oxothio, dioxo, and dithio tautomers are the most stable. These results correspond to the known experimental data. Infrared spectra of the investigated compounds were recorded for the region 4000-150 cm^-1, and the characteristic bands were compared with ab initio calculated frequencies at the HF/3-21G^(*)* level.     

Synthesis and theoretical characterization of some new 4‐substituted‐1,3‐diphenyl‐5‐thioxo‐4,5‐dihydro‐1H‐1,2,4‐triazoles with potential pharmacological activity

Synthesis of some new triazoles fused to triazoles 5a–c or thiadiazoles 6a–c and the thiol‐thione tautomeric equilibrium study of the title compounds are reported. The “rule of five” and complementary criteria of pharmacokinetic properties were determined to predict whether these compounds are orally bioavailable. Semiempirical parameterizations have been critically benchmarked for the thiol‐thione tautomeric equilibrium against the DFT calculations. It was shown that unlike the AM1 and PM3 Hamiltonians, which erroneously predict higher stability of the thiol tautomer, the newly developed RM1 Hamiltonian, on the other hand, predicts energetics of this equilibrium in excellent agreement with the DFT results. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:713–718, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20499     

AM1 and PM3 Study of Tautomerism of Hypoxanthine in the Gas and Aqueous Phases

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, dipole moments, and ionization potentials for the eight possible tautomers of hypoxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimization. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two keto tautomers H17 and H19 are the predominant species at room temperature in the gas and aqueous phase. However, the tautomer H17 is the more dominant species in gas phase, while the H19 tautomer is the more dominant species in the aqueous phase. Comparison with available experimental data provides support for the results derived from theoretical computations. The entropy effect on the Gibbs free energy of hypoxanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of the equilibrium constant.     

UV and MO study on the deprotonation of some 2-aryl-Δ2-1,3,4-oxadiazoline-5-thiones

Substituent effects on the deprotonation processes of a series of 2-aryl-Δ²-1,3,4-oxadiazoline-5-thione (1) derivatives have been studied experimentally as well as theoretically. The acid dissociation constants pK_a have been determined spectrophotometrically in ethanol-water solutions (7.5-92.5%) and vary between 3.76 and 5.80. Semiempirical molecular orbital (MO) calculations (AM1 and PM3) were used for the investigation of the existence of possible tautomeric thione and thiol forms of the studied compounds. Strong correlation between the pK_a values and the deprotonation enthalpies were evaluated.     

Reconsideration of solvent effects calculated by semiempirical quantum chemical methods

AM1 and PM3 semiempirical calculations are reported for the solvent effects on the tautomeric equilibria of 2-pyridone/2-hydroxypyridine and 4-pyridone/4-hydroxypyridine in the gas phase and solution. The solvent effects on the tautomeric equilibria were investigated by self-consistent reaction field (SCRF) theory implemented in the AMPAC and MOPAC program in two different ways: one in which all the solvent relaxation is included in the quantum mechanics and the total energy must be corrected for the solvent change in energy, method A; and a second in which the quantum mechanics directly includes this term, method B. The calculated (AM1, method A) tautomeric equilibrium constants (log K₁) for 2-pyridone in the gas phase, cyclohexane, chloroform, and acetonitrile are ?0.3, 0.3, 0.8, and 1.3, respectively, in good agreement with the experimental data (?0.4, 0.24, 0.78, and 2.17, respectively). For 4-pyridone/4-hydroxypyridine differences between calculated log K₁ for the gas phase, chloroform and acetonitrile (?6.0, ?2.6, and ?1.2, respectively) and experimental data (< ?1, 0.11, and 0.66, respectively) are larger but the experimental values are also less certain. The experimental acetonitrile data are disturbed by specific interactions. An extension of the SCRF for aqueous solutions is reviewed. © 1993 John Wiley & Sons, Inc.     

PM3 study of the proton affinities of 2-, 3-, and 4-monosubstituted pyridines in the gas phase

Heats of formation (ΔH_f) and proton affinities (PA) of 2-, 3-, and 4-monosubstituted pyridines in the gas phase are calculated using the AM1 and PM3 semiempirical methods. The following substitutents are considered: NO₂, CN, CF₃, CHO, F, Cl, COCH₃, H, CH₃, OCH₃, SCH₃, NH₂, and N(CH₃)₂. The results are compared with the experimental data. Both methods reproduce the ΔH_f with comparble accuracy; the rms deviations are 4.1 (AM1) and 4.5 kcal/mol (PM3) for the free bases and 9.5 (AM1) and 9.7 kcal/mol (PM3) for their conjugated acids. The PA are systematically underestimated by both methods, but AM1 appears to be clearly better than PM3 for reproducing the experimental values. The rms deviations for AM1 and PM3 are 5.1 and 9.6 kcal/mol, respectively. This is due to a cancellation of systematic errors in the calculated ΔH_f in the AM1 case and to a summation of the errors in the PM3 case. Both methods correctly reproduce conformations of the molecules under consideration.     

Comparative parametric method 5 (PM5) study of trans-stilbene

In this work we report a comparative Austin method 1 (AM1), parametric method 3 (PM3), and parametric method 5 (PM5) studies for trans-stilbene in its ground, excited (singlet and triplet), and ionic (positive and negative polarons and bipolarons) states. We evaluated the accuracy of the recently developed PM5 method. PM5 and AM1 predict a non-planar ground and singlet states for trans-stilbene, while PM3 predicts planar ones, which is in agreement with the available experimental data. In general the PM3 and PM5 bond lengths are superior to AM1 while AM1 bond angles are superior to PM3 and PM5 when compared with available experimental data. The PM5 underestimates the cis–trans isomerization energy and and it is not a quite reliable method for the calculation of relative IP values. The presumed PM5 superior performance against AM1 and PM3 was not observed for the stilbene structures.     

Investigation of the structure of and the properties of the potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones in the gaseous and aqueous phases using the AM1 semi-empirical method

Potentially tautomeric 1,2,3,4-tetrahydro-5,7-dimethyl-6H-pyrrolo[3,4-d]pyridazine-1,4-diones and their fixed tautomeric forms have been studied in order to predict their tautomeric equilibrium constants and pK_a values using semi-empirical AM1 quantum-chemical calculations at the SCF level in the gas phase and in aqueous solution. Hydroxy-oxo forms were found to be more stable than dioxo and dihydroxy forms. The results obtained from the tautomeric equilibria and basicity calculations are in good agreement with experimental data.     

Analysis of the core-repulsion functions used in AM1 and PM3 semiempirical calculations: Conformational analysis of ring systems

The AM1 and PM3 potential energy surfaces of cyclopentane have been compared and the energy difference between two (boat and chair) cyclohexane conformers analyzed. The effects of reparameterization and different core-repulsion functions (CRFs) have been studied. The H? H, C? H, and C? C CRF energy contributions have been calculated separately. The results show that the CRF energy corrections stabilize the correct (MM2 and ab initio) geometries. The PM3 equilibrium geometry of cyclopentane is closer to the MM2 and ab initio results than the AM1 geometry. It is known that above 190 pm the AM1 H? H CRF curve is smooth and negative but the PM3 H? H CRF curve has a trough and a shoulder. It has been shown that this latter oscillation is not damped by other parameters. As a result, the H? H PM3 energy gradient curve is different from the quasilinear AM1 and ab initio gradient curves. © 1993 John Wiley & Sons, Inc.     

共轭烯烃的分子几何构型、电子结构和生成热的DMM和AM1、PM3的比较研究

运用Ｄｅｌｆｔ分子力学（ＤＭＭ）力场和程序以及半经验分子轨道ＡＭ１和ＰＭ３方法计算研究了丁二烯、苯、甲苯、联苯、苯乙烯、富烯、、环辛四烯、［２，２］对环烷和菲等１０个共轭烯烃分子的几何构型、电子结构和生成热．ＤＭＭ计算的几何构型和生成热与实验结果相吻合，电荷分布结果与从头计算结果较接近．ＡＭ１和ＰＭ３计算的几何构型较好，但计算的生成热与实验结果偏差较大．ＰＭ３计算值比ＡＭ１的稍好．     

苯基及取代苯基四唑异构反应的量子化学研究

与四唑相同，对位取代苯基四唑有两种异构体（见图1）.几十年来，实验工作者对这类化合物在医药和农业等方面的应用研究表现出浓厚兴趣［‘-‘1.最近，我们用从头计算和PM3等方法研究了四唑两种异构体间异构化反应的机理问.为了探明这类反应的取代基效应，本文报导用PM3方法[6]     

Tautomeric equilibria of heterocyclic molecules. A test of the semiempirical AM1 and MNDO-PM3 methods

Tautomeric equilibria (mainly of the lactam-lactim type) for a rather large number of six-membered heterocyclic molecules are calculated by the semiempirical AM1, MNDO-PM3, and MNDO methods. Except for compounds with adjacent pyridine-like lone pairs both AM1 as well as MNDO-PM3 give rather reliable predictions for relative stabilities of the various tautomeric species–comparable to quite high level ab initio calculations. The known errors associated with MNDO in the treatment of heterocyclic tautomerism are thus largely corrected in AM1 as well as MNDO-PM3. For 2-hydroxypyridine-pyrid-2(1H)-one the effect of self-association is less satisfactorily described by MNDO-PM3 than by AM1. MNDO-PM3 calculated relative stabilities of methylated derivatives are, however, in considerably closer agreement with experimental values than those obtained by AM1. Ionization potentials, especially those for lone-pair orbitals, are overestimated by all three semiempirical methods. MNDO-PM3 results for nitrogen lone-pair orbital energies are slightly better than those obtained by the AM1 or MNDO method.     

Special Features of the Steric and Electronic Structure of Bis(3-imino-1-isoindolinylideneamino)arylenes According to Data of the AM1 Method

Using the semiempirical AM1 method stationary points have been found on the potential energy surfaces for the internal rotation of 1,3-bis(3-imino-1-isoindolinylideneamino)benzene and 2,6-bis(3-imino-1-isoindolinylideneamino)pyridine, and also for their tautomeric forms. Energy barriers for the in-plane inversion of the terminal imino groups and for the tautomeric conversions involving them have been determined. It was shown that the molecules of these compounds are structurally flexible.     

The applicability of AM1 and PM3 semi-empirical methods for the study of N-H bond dissociation enthalpies and ionisation potentials of amine type antioxidants

A study of 40 para-substituted anilines is presented. These serve as model structures of amine type antioxidants. Molecules and their radical structures were studied using the AM1 and PM3 quantum chemical methods in order to calculate the N-H bond dissociation enthalpies (BDEs) and ionisation potentials (IPs) which are among the most important characteristics of antioxidants. Calculated BDEs were compared with available experimental values and the results of DFT calculations to ascertain the suitability of AM1 and PM3 methods for amine BDEs calculation. The results show that both methods reproduce experimental BDEs and DFT data satisfactorily. Comparison with experimental data shows that AM1 and PM3 methods overestimate the IP values. The results also indicate that dependences of N-H bond BDEs and IPs on Hammett constants of the substituents are linear.     

Molecular orbital and DFT studies of the alimemazine radical cation

Semiempirical molecular orbital methods including CNDO, MNDO, AM1 and PM3, and density function theory method B3LYP/3-21G(d) were employed in the study of the alimemazine radical cation. It was found that PM3 was much better than CNDO, MNDO and AM1 in the structural optimization. The bond lengths and bond angles by PM3 were close to the experimental data, and comparable with the results by the density function theory method.