Electronic structure and conformational flexibility of 1,2-dihydropyridine, 1,2- and 1,6-dihydropyrimidines,and their ylide derivatives

Molecular and electronic structures of 1,2-dihydropyridine, 1,2- and 1,6-dihydropyrimidine, and their oxo, imino, and methylene derivatives were studied by the semiempirical quantum-chemical AM1 method. In all compounds, the heterocycle exhibits a high conformational flexibility. The transition from a planar equilibrium conformation to a distorted sofa conformation with the =C-NH-C-C(N)= torsion angle of ±20° causes an increase in the energy by less than 1.7 kcal mol^–1. All molecules have similar -electronic structures, which, apparently, determines the similarity in their conformational behavior. The bending strain and the nonaromatic character of the cyclic -system are the factors that stabilize the nonplanar conformation of the ring in unsubstituted dihydroazines and ylide derivatives, respectively.Translated fromIzvestiva Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1934–1937, August, 1996.     

Effect of benzannelation on the conformational flexibility of the rings in oxo, imino, and methylene derivatives of cyclohexa-1,4-diene

The effect of benzannelation on the equilibrium conformation and flexibility of the dihydrocycle in cyclohexa-1,4-dienone,para-quinone, and their imino and methylene analogs was studied by the semiempirical quantum-chemical AM1 method. The equilibrium conformations of the carbonyl derivatives are planar. In the imino- and methylene-substituted analogs, the dihydrocycle adopts a boat conformation due to repulsions between substituted analogs, the dihydrocycle adopts a boat conformation due to repulsions between the hydrogen atoms at the exocyclic double bond and in theperi positions of the benzene rings. Annelation of cyclohexa-2,5-dien-1-one andpara-quinone with benzene rings at the C=C double bonds causes an increase in the conformational flexibility of the partially hydrogenated ring owing to an increase in the bending strain in the first compound and a decrease in the conjugation between the carbonyl groups and the remaining part of the molecule in the second compound. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 388–390, March, 1998.     

Effect of electronic interactions between double bonds on the conformational flexibility of 1,4-cyclohexadiene

The electronic structure of 1,4-cyclohexadiene for various angles between the double bond planes has been calculated by the AM1 method. The effects of through-bond and through-space interactions, which result in flattening and unflattening, respectively, are oppositely directed. These effects are specified for various bending angles. In addition to steric factors, electronic factors affect the conformational flexibility of 1,4-cyclohexadiene.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1676–1677, September, 1994.     

Conformational flexibility of 1,4-dihydroazine carbonyl derivatives

Summary The molecular geometry of 4-oxo derivatives of 1,4-dihydropyridine, 1,4-dihydropyrimidine, 1,4-dihydropyridazine, and 1,4-dihydro-1,3,5-triazine has been calculated by the semi-empirical quantum-chemical AM1 method. It could be shown that the dihydrocycle in these compounds is not conformationally rigid. Changing the angle between the endocyclic double bond planes ±15° causes less than 1 kcal/mol increase of energy.

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Konformative Flexibilität von 1,4-Dihydroazin-carbonyl-Derivaten (Kurze Mitt.)

Zusammenfassung Die molekulare Geometrie von 4-Oxo-Derivaten von 1,4-Dihydropyridin, 1,4-Dihydropyrimidin, 1,4-Dihydropyridazin und 1,4-Dihydro-1,3,5-triazin wurde mittels der semiempirischen quantenchemischen AM1-Methode berechnet. Es konnte gezeigt werden, daß der zweifach hydrierte Ring in diesen Verbindungen nicht starr ist. Eine Änderung des Winkels zwischen den Ebenen der endocyclischen Doppelbindungen um ±15° bewirkt eine Energieerhöhung von weniger als 1 kcal/mol.

     

Molecular and electronic structures and conformational analysis of derivatives of 9-nitroanthracene, anionic σ-complexes

Potassium 10-methoxy-9-nitroanthracenide was studied by X-ray diffraction analysis. The central ring of the anthracene fragment adopts an asymmetrically flattened boat conformation. The bond lengths in the C(Ar)−C(NO₂)−C(Ar) fragment are indicative of the presence of conjugation between the π-systems of the benzene rings and the nitro group owing to a substantial contribution of theaci form to the structure of the nitro group. Quantum-chemical calculations of anionic σ-complexes of 9-nitroanthracene derivatives were performed. In all cases, the central ring adopts two conformations with the pseudoaxial and pseudoequatorial orientations of the substituents at the saturated C(10) atom, respectively. The relative stability of the conformers and the factors determining the stability were considered. The minima on the potential energy surface have a flattened shape in spite of relatively high barriers to the conformational transition (2–4 kcal mol⁻¹). The deviation of the C(Ar)−C(Ar)−C(sp³)−C(Ar) torsion angle from the equilibrium value by ±20° causes an increase in the energy of the anion by less than 1 kcal mol⁻¹. The effect of the substituents on the charge distribution was considered. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 438–443, March, 1998.     

Influence of steric and electronic effects of substituents on the molecular structures and conformational flexibility of 1,8-naphthalenedicarboximides

A series of 1,8-naphthalenedicarboximide derivatives containing substituents of different steric and electronic nature were studied by X-ray diffraction analysis.Ab initio quantumchemical calculations in the HF/3–21G approximation demonstrated the high conformational flexibility of the imide tetrahydro ring in the molecules of these compounds. The electronic nature of the substituents has no effect on the geometry and conformational flexibility of naphthalenedicarboximides due to weak conjugation between the imide and naphthalene fragments in the molecules. However, the steric effects of the bulky substituents noticeably affect the equilibrium geometry of the imide ring by increasing its conformational flexibility. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 68–73, January, 2000.     

Influence of steric and electronic effects of substituents on the molecular structures and conformational flexibility of 1,8-naphthalenedicarboximides

A series of 1,8-naphthalenedicarboximide derivatives containing substituents of different steric and electronic nature were studied by X-ray diffraction analysis.Ab initio quantumchemical calculations in the HF/3–21G approximation demonstrated the high conformational flexibility of the imide tetrahydro ring in the molecules of these compounds. The electronic nature of the substituents has no effect on the geometry and conformational flexibility of naphthalenedicarboximides due to weak conjugation between the imide and naphthalene fragments in the molecules. However, the steric effects of the bulky substituents noticeably affect the equilibrium geometry of the imide ring by increasing its conformational flexibility. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 68–73, January, 2000.     

Molecular structure and conformation flexibility of 2-oxo- and 2-thioxo-1,2,3,4-tetrahydropyrimidines and their derivatives

The conformational flexibility and effects of the substituents in 2-oxo- and 2-thioxo-1,2,3,4-tetrahydropyrimidines were studied by the semiempirical quantum-chemical AM1 method. The substituents at the double bond have no appreciable effect on the conformational characteristics of the heterocycle. The introduction of substituents to the saturated carbon atom results in the conversion of the tetrahydrocycle to a half-chair conformation and in a substantial decrease in the ring flexibility. The results of calculations are confirmed by the X-ray study of both compounds. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya No. 11, pp. 1941–1946, November, 1997.     

Conformational flexibility of partially hydrogenated rings in the repeating units of rigid-chain heterocyclic polymers

The conformational flexibility of partially hydrogenated rings in naphthylimide, naphthalic anhydride, and some of their derivatives used as model compounds for the repeating unit in rigid-chain heterocyclic polymers, was studied by the semiempirical quantum-chemical AM1 method. The partially hydrogenated rings in all of these compounds possess conformational flexibility. Transition from a planar equilibrium form to a distorted sofa conformation with a torsion angle of ±20° results in an increase in the energy of less than 1 kcal mol⁻¹. The high flexibility of partially hydrogenated rings, along with other factors, can cause finite length of the Kuhn segment in rigid-chain heterocyclic polymers. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya. No. 1, pp. 64–66, January 1997.     

Cycle mobility in 1,4-dihydropyridine and its monoalkyl and phenyl derivatives

The conformational mobility of the 1,4-dihydropyridine cycle has been studied by the molecular mechanics method. It was shown that the N(1) and C(4) atoms are displaced asymmetrically from the plane of the double bonds. The asymmetry is the result of conjugation between the nitrogen lone pair and the systems of the double bonds. The influence of alkyl and phenyl substituents at the carbon atoms on the equilibrium conformation and cycle mobility has been investigated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1217–1219, July, 1993.     

给、吸电子基团对吡嗪衍生物电子结构影响的DFT研究

采用B3LYP方法在6—31G^#基组水平上优化了对位取代吡嗪衍生物的几何构型，利用TD—DFT方法计算了它们的前线分子轨道能级和电子光谱．结果表明，带有给、吸电子基团对吡嗪衍生物与苯、吡啶相比，也具有很好的共轭性；随着分子共轭链的增长，分子的偶极矩增大，前线分子轨道能级差减小，最大吸收波长发生红移．对于具有相同共轭链的同分异构体，推电子基团与具有给电子性质的共轭链相连，则分子的电荷转移明显，导致偶极矩增大，前线分子轨道能级间的电子跃迁更容易；吸电子基团与具有给电子性质的共轭链相连，情况正好相反，这些结果对分子设计有重要意义。     

Structure and conformational flexibility of hexamethyldiperoxacyclononane

3,3,6,6,9,9-Hexamethyl-1,2,4,5-tetraoxacyclononane, one of the most thermally stable organic peroxides, has been studied by X-ray structural analysis. Possible conformations of this compound have been calculated by the molecular mechanics method.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 110–112, January, 1995.     

A CoMFA analysis with conformational propensity: An attempt to analyze the SAR of a set of molecules with different conformational flexibility using a 3D-QSAR method

CoMFA analysis, a widely used 3D-QSAR method, has limitations to handle a set of SAR data containing diverse conformational flexibility since it does not explicitly include the conformational entropic effects into the analysis. Here, we present an attempt to incorporate the conformational entropy effects of a molecule into a 3D-QSAR analysis. Our attempt is based on the assumption that the conformational entropic loss of a ligand upon making a ligand-receptor complex is small if the ligand in an unbound state has a conformational propensity to adopt an active conformation in a complex state. For a QSAR analysis, this assumption was interpreted as follows: a potent ligand should have a higher conformational propensity to adopt an `active-conformation'-like structure in an unbound state than an inactive one. The conformational propensity value was defined as the populational ratio, N<sub>active</sub>/N<sub>stable</sub>, of the number of energetically stable conformers, N<sub>stable</sub>, to the number of `active-conformation'-like structures, N_active. The latter number was calculated by counting the number of conformers that satisfied the structural parameters deduced from the active conformation. A set of SAR data of imidazoleglycerol phosphate dehydratase inhibitors containing 20 molecules with different conformational flexibility was used as a training set for developing a 3D structure-activity relationship by a CoMFA analysis with the conformational propensity value. This resulted in a cross-validated squared correlation coefficient of the CoMFA model with the conformational propensity value (R ² _cross = 0.640) higher than that of the standard CoMFA model (R ² _cross = 0.431). Then we evaluated the quality of the CoMFA models by predicting the inhibitory activity for a new molecule.     

The effect of substituents on the conformational mobility of the heterocycle in 1,4-dihydropyrimidine and its derivatives

The equilibrium geometry of 1,4-dihydropyrimidine, 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, and their alkyl (Me, Et, Prⁱ, Bu^t) and phenyl derivatives has been calculated by molecular mechanics method. The equilibrium conformation of unsubstituted molecules is planar, but it is easily transformed to the boat conformation with a small change in the conformational energy. The effect of substituents on the geometry and conformational mobility of the dihydropyrimidine ring has been studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1394–1397, August, 1994.     

A molecular mechanics and semiempirical conformational analysis of the herbicide diuron inhibitor of photosystem II

The potential energy surface (PES) for the herbicide diuron (DCMU), a photosystem II inhibitor, has been extensively investigated using the quantum-mechanical semiempirical molecular orbital methods AM1 and PM3 and molecular mechanics method. A detailed conformational search has been carried out which revealed the occurrence of four genuine minimum energy structures. The relative stability of the conformers and rotational barriers to conformational interconversion were evaluated using distinct theoretical approaches. The results showed that thetrans form of the diuron molecule is more stable than thecis form in all methods, and so it may possibly be the biologically active isomer.     

Conformational flexibility and aromaticity of azanaphthalenes

Conformational flexibility of naphthalene and its different mono-and diaza analogues has been studied by MP2/6-31G(d, p) quantum chemical computations. It is shown that all molecules possess a considerable conformational flexibility. The out-of-plane deformation energy of both a bicyclic π-system on the whole and separate rings directly depends on the degree of aromaticity of the conjugated system. Effects of the amount and arrangement of nitrogen atoms on conformational features and aromaticity of the molecules considered were analyzed.     

Electronic structure and conformational study of thiobiurets

Quantum mechanical calculations at all valence complete neglect of differential overlap (CNDO/2) and self-consistent charge extend Huckel (SCC-EH) and the Pi electron Pariser-Parr-Pople with limited configuration interaction (PPP-LCI) levels of approximation have been accomplished for monothiobiuret and dithiobiuret. From the calculated results, a discussion of the electronic structure, photoelectron and electronic spectra and the conformational stability are given. The electronic and¹H nmr spectra are also reported. A trans-cis-CONHCS-structure is found to be the stable conformation for monothiobiuret consistent with other evidences.     

Electronic structure of aryl- and carbonyl-containing diazomethane derivatives,as disclosed by photoelectron spectroscopy

Vertical ionization energies (IE) of aryl and carbonyl derivatives of diazomethane have been determined by photoelectron spectroscopy. The types of the highest occupied molecular orbitals (HOMO) in these molecules are identified.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 325–328, February, 1993.     

Electronic structure and stability of polymorphous modifications of titanium monocarbide

The electronic structures and stabilities of five polymorphous modifications (PM) of titanium monocarbide, TiC, with the NaCl (Bl), CsCl (B2), zinc blende (B3), würtzite (B4), and NiAs (B8) structural types. were studied by the non-empirical, self-consistent linear “muffin-tin” orbital-tight-binding (LMTO-TB) method. The equilibrium unit cell volumes. latice parameters, and the densities of electronic states were calculated. Depending on the structural type (coordination number, CN), the PM of TiC possess essentially different conducting properties (semimetallic for CN 6 (B1, B8), metallic for CN 8 (B2), and semiconducting for CN 4 (B3, B4)). Based on the results of calculations of the total band energies, it was found that the stabilities of these PM of TiC decrease in the order B1>B8>B3>≈B4>B2. The nature of chemical bonding in the five PM of TiC was analyzed in the tight-binding approximation with EHT parametrization. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1821–1824, October, 2000.     

The influence of substituents in the quinone dihydrocycle of anthroneylidene molecules on the polymer chain rigidity

The effect of substituents on the conformational rigidity of the six-membered dihydrocycle constituting the repeating unit of heterocyclic polymers was studied by the semiempirical AM1 method and by conformational analysis. The polymer rigidity can be controlled over a wide range by choosing appropriate substituents in the dihydrocycle. An original procedure was proposed for calculating the Kuhn segment of the copolymer taking into account the Boltzmann factor. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 797–801, May, 2000