Ethyl 3,5‐dimethyl‐4‐phenyl‐1H‐pyrrole‐2‐carboxylate

In the title compound, C₁₅H₁₇NO₂, the ethoxy­carbonyl group is anti with respect to the pyrrole N atom. The angle between the planes of the phenyl and pyrrole rings is 48.26 (9)°. The mol­ecules are joined into dimeric units by a strong hydrogen bonds between pyrrole N—H groups and carbonyl O atoms. The geometry of the isolated mol­ecule was studied by ab initio quantum mechanical calculations, employing both molecular orbital Hartree–Fock (MO–HF) and density functional theory (DFT) methods. The minimum energy was achieved for a conformation where the angle between the planes of the phenyl and pyrrole rings is larger, and that between the ethoxy­carbonyl and pyrrole planes is smaller than in the solid‐state mol­ecule.     

Bond–antibond analysis of internal rotation barriers in glyoxal and related molecules: Where INDO fails

Ab initio and INDO LCBO–MO calculations are carried out on glyoxal, 1,3-butadiene, and acrolein in order to analyze the qualitative failure of INDO -like methods to describe conformation energies in these molecules. Following the method of Brunck and Weinhold for ethanelike systems we identify the principal bond–antibond interactions contributing to the glyoxal barrier, their dependence on dihedral angle and substituent, and their relative magnitudes as calculated by ab initio and INDO SCF–MO theory. We find a gross disparity in the INDO representation of π* interactions which leads to a grossly exaggerated estimate of the stability of gauche conformers in these molecules. These findings appear to have serious implications for the applicability of INDO -like theories to conformational problems in π-bonded molecules, including those of biological interest.     

1H, 13C, 17O NMR and quantum‐chemical study of the stereochemistry of the sulfoxide and sulfone derivatives of 3‐arylidene‐1‐thioflavan‐4‐one epoxides

The oxidation of the trans,cis‐( 2 ) and trans,trans‐epoxides ( 3 ) of differently substituted (Z)‐3‐arylidene‐1‐thioflavan‐4‐ones ( 1 ) with dimethyldioxirane (DMD) yielded the appropriate sulfoxides ( 4, 5 ) and sulfones ( 6, 7 ). The structures were elucidated by the extensive application of one‐ and two‐dimensional ¹H, ¹³C and ¹⁷O NMR spectroscopy. The conformational analysis was achieved by the application of ³J(C,H) coupling constants, NOESY responses and ab initio calculations. The preferred ground‐state conformers (twisted envelope‐A, twisted envelope‐B for 6 and twisted envelope‐A, envelope‐B for 7 ) were obtained as global minima of the theoretical ab initio MO study and also the examination of the ¹⁷O and ¹³C chemical shifts, calculated for the global minima structures of the sulfone isomers by the GIAO method. Analogous results, obtained for the sulfoxide isomers ( 4, 5 ), not only led to the preferred conformers but also gave evidence for the trans arrangement of the 2‐Ph group and the oxygen atom of the S?O group. Chemical shift differences between the isomers, sulfoxides and sulfones were corroborated by ab initio calculations of the anisotropic effects of the oxirane ring and the S?O and SO₂ groups. Copyright © 2003 John Wiley & Sons, Ltd.     

Optimization of equilibrium geometries and transition structures

A modified conjugate gradient algorithm for geometry optimization is outlined for use with ab initio MO methods. Since the computation time for analytical energy gradients is approximately the same as for the energy, the optimization algorithm evaluates and utilizes the gradients each time the energy is computed. The second derivative matrix, rather than its inverse, is updated employing the gradients. At each step, a one-dimensional minimization using a quartic polynomial is carried out, followed by an n-dimensional search using the second derivative matrix. By suitably controlling the number of negative eigenvalues of the second derivative matrix, the algorithm can also be used to locate transition structures. Representative timing data for optimizations of equilibrium geometries and transition structures are reported for ab initio SCF –MO calculations.     

Ab initio studies of hydrogen bond formation in methyl cyanide or methyl isocyanide and methanol systems

CH₃CN ? HOCH₃ and CH₃NC ? HOCH₃ hydrogen-bonded systems have been studied theoretically by ab initio MO methods using a 4–31 G basis set at their equilibrium geometries. The stabilization energies of these hydrogen bonds are 5.4 and 5.9 kcal/mol, respectively. The nature of these hydrogen bonds is discussed in the light of frontier orbital theory and the topological properties of the charge density of the chemical bond.     

Theoretical Prediction of Substituent Effects on the Intrinsic Folding Properties of β‐Peptides

A systematic conformational analysis on blocked β‐amino acids as constituents of β‐peptides by ab initio MO theory reveals that the conformer pool of β‐peptide monomers is essentially determined by the conformation of simple submonomer fragments. The influence of single and multiple substitutions at the C(α) and C(β) backbone atoms on the intrinsic folding properties of the monomers was estimated both in the single‐molecule approximation and in a polar solvent continuum, applying a quantum‐chemical SCRF model. Substitution at C(β) has a higher impact on the β‐amino acid conformation than a substitution at C(α). It can be shown that the conformations of important periodic secondary structures in β‐peptides belong to the conformer pool of the monomers, even for those secondary‐structure elements where H‐bond formation appears only in longer sequences. Rules for design of special secondary‐structure types by selection of an actual substituent pattern in the β‐amino acid constituents have been derived within the monomer approach.     

Das SCF–MO–P(LCGO)-Verfahren und seine Varianten

A modification of the SCF –MO –LCGO method is proposed in the form of a qualitative ab initio method. Naphthalene is treated as a test case; good agreement between calculated and experiemental results is obtained. The capabilities of the method for quantum-chemical calculations are discussed.     

5β,6β‐Epoxy‐17‐oxoandrostan‐3β‐yl acetate and 5β,6β‐epoxy‐20‐oxopregnan‐3β‐yl acetate

In the title compounds, C₂₁H₃₀O₄, (I), and C₂₃H₃₄O₄, (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis‐(5β,10β)‐fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5β,6β‐epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree–Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.     

Theoretical study of “protonated pyruvate”: A methylhydroxycarbene—carbon dioxide complex—implications for the decarboxylation of pyruvic acid

Two conformers of protonated pyruvate, CH₃C⁺(OH)COO, with the OH group either trans or cis to the methyl group and the carboxylate group in the C? C? C plane have been studied using the ab initio SCF/3-21G method, as well as by some semiempirical AM1 calculations. Both ab initio SCF and AM1 curves for the potential energy as a function of the C? COO distance exhibit a minimum corresponding to a complex of methylhydroxycarbene, CH₃COH, associated with carbon dioxide, but only the AM1 curves predict an inner minimum corresponding to a covalently bonded protonated pyruvate molecule with a C? COO distance of 1.6–1.7 Å. The two models also disagree on the dissociation pathway for pyruvic acid, with the AM1 calculations predicting formation of acetyl and HOCO radicals while the ab initio method predicts dissociation into methylhydroxycarbene and carbon dioxide following an initial intramolecular proton transfer. The weakly bound complexes of methylhydroxycarbene and carbon dioxide have been studied in some detail using ab initio SCF and MP2 methods in conjunction with 6-311G** basis sets, obtaining equilibrium geometries and vibrational frequencies. In addition, the lactone-type isomer of protonated pyruvate, which contains a C? C? O ring, was also studied. The conclusions of these calculations are consistent with those from earlier work using the smaller 3-21G basis set. The most stable complex is predicted to occur between trans-methylhydroxycarbene and carbon dioxide where substantial stabilization is provided by an OH ? OC hydrogen bond. © 1993 John Wiley & Sons, Inc.     

Chelation of carbocations by polyethers and polyamines

Chelates formed by carbocations and cyclic polyethers and polyamines are studied with semiempirical and ab initio MO methods.     

Wellenmechanische Absolutrechnungen an Molekülen und Atomsystemen mit der SCF?MO?LC(LCGO) Methode. IV. Das Äthylen (C2H4)

The C₂H₄ was investigated ab initio for the equilibrium distance of the centers, taking all 16 electrons into account, using the Allgemeines Programmsystem/SCF ? MO ? LC (LCGO ) Methode. A total energy of ?76.77 a.u. and an ionization energy of 10.55 eV were found.     

Theoretical study of the intermolecular hydrogen bond interaction for furan-HCl and furan-CHCl<Subscript>3</Subscript> complexes

The nature of the intermolecular hydrogen bond for the furan-HCl and furan-CHCI₃ complexes has been studied using ab initio calculations with MP2 level of theory. The new hydrogen bond type of C(CI)-H...O and π interactions are studied also. It is shown that, for the optimized geometries of furan-CHCI₃, C-H bond lengths contract and vibrational frequencies are blue-shifted, while for the furan-HCl complex, H-CI bond lengths elongate and vibrational frequencies are red-shifted. In addition, the NBO analysis indicates that, for the furan-CHCI₃ complex, the charge transfers from the lone pair of the proton acceptor to both σ *(CH) antibonding MO and lone pairs of CI atom.     

Molecular Structure of ortho-Fluoronitrobenzene Studied by Gas Electron Diffraction and Ab Initio MO Calculations

The molecular structure of ortho-fluoronitrobenzene (o-FNB) has been investigated by gas-phase electron diffraction and ab initio MO calculations. The geometrical parameters and force fields of o-FNB were calculated by ab initio and DFT methods. The obtained force fields were used to calculate vibrational amplitudes required as input parameters in an electron diffraction analysis. Within the experimental error limits, the geometrical parameters obtained from the gas-phase electron diffraction analysis are mostly in agreement with the results obtained from the ab initio calculations. The main results are: the molecular geometry of o-FNB is nonplanar with a dihedral angle about C–N of 38(3)°. The r _g (C–F) bond is shortened to 1.307(13) Å in comparison with r _g (C–F) = 1.356(4) Å in C₆H₅F.     

Helix Formation and Folding in γ‐Peptides and Their Vinylogues

A complete overview of all possible periodic structures with characteristic H‐bonding patterns is provided for oligomers composed of γ‐amino acids (γ‐peptides) and their vinylogues by a systematic conformational search on hexamer model compounds employing ab initio MO theory at various levels of approximation (HF/6‐31G*, DFT/B3LYP/6‐31G*, SCRF/HF/6‐31G*, PCM//HF/6‐31G*). A wide variety of structures with definite backbone conformations and H‐bonds formed in forward and backward directions along the sequence was found in this class of foldamers. All formally conceivable H‐bonded pseudocycles between 7‐ and 24‐membered rings are predicted in the periodic hexamer structures, which are mostly helices. The backbone elongation in comparison to α‐ and β‐peptides allows several possibilities to realize identical H‐bonding patterns. In good agreement with experimental data, helical structures with 14‐ and 9‐membered pseudocycles are most stable. It is shown that the introduction of an (E)‐double bond into the backbone of the γ‐amino acid constituents, which leads to vinylogous γ‐amino acids, supports the folding into helices with larger H‐bonded pseudocycles in the resulting vinylogous γ‐peptides. Due to the considerable potential for secondary‐structure formation, γ‐peptides and their vinylogues might be useful tools in peptide and protein design and even in material sciences.     

Conformation and tautomerism of methoxy‐substituted 4‐phenyl‐4‐thiazoline‐2‐thiones: a combined crystallographic and ab initio investigation

4‐Phenyl‐4‐thiazoline‐2‐thiol is an active pharmaceutical compound, one of whose activities is as a human indolenamine dioxygenase inhibitor. It has been shown recently that in both the solid state and the gas phase, the thiazolinethione tautomer should be preferred. As part of both research on this lead compound and a medicinal chemistry program, a series of substituted arylthiazolinethiones have been synthesized. The molecular conformations and tautomerism of 4‐(2‐methoxyphenyl)‐4‐thiazoline‐2‐thione and 4‐(4‐methoxyphenyl)‐4‐thiazoline‐2‐thione, both C₁₀H₉NOS₂, are reported and compared with the geometry deduced from ab initio calculations [PBE/6‐311G(d,p)]. Both the crystal structure analyses and the calculations establish the thione tautomer for the two substituted arylthiazolinethiones. In the crystal structure of the 2‐methoxyphenyl regioisomer, the thiazolinethione unit was disordered over two conformations. Both isomers exhibit similar hydrogen‐bond patterns [R₂²(8) motif] and form dimers. The crystal packing is further reinforced by short S…S interactions in the 2‐methoxyphenyl isomer. The conformations of the two regioisomers correspond to stable geometries calculated from an ab initio energy‐relaxed scan.     

Intramolecular chelation of Zn2+ by α‐ and β‐mercaptocarboxamides. A parallel ab initio and polarizable molecular mechanics investigation. Assessment of the role of multipole transferability

α‐ and β‐mercaptocarboxamides constitute the Zn²⁺‐ligating entity of several highly potent metalloenzyme inhibitors. We have studied their interaction energies with Zn²⁺ using the polarizable molecular mechanics procedure SIBFA, and compared them to the corresponding ab initio supermolecule ones. Such validations are necessary to subsequently undertake simulations on complexes of Zn²⁺–metalloenzymes with inhibitors. If the distributed multipoles and polarizabilities are those derived for each ligand in its appropriate Zn²⁺‐binding conformation, a close reproduction of the ab initio binding energies is afforded. However, this representation is not tractable upon increasing the size of the ligands and/or to explore a continuum of binding conformations. This makes it necessary to construct the ligands by resorting to a library of constitutive fragments, namely in this case methanethiolate, formamide, and methane covalently connected together. A close reproduction of the ab initio interaction energies is enabled, but only if the ligand–ligand interactions are computed simultaneously with those occurring with Zn²⁺. This representation accounts for the nonadditivity occurring in the Zn²⁺–methanethiolate–formamide complex, and justifies the use of the distributed multipoles on the fragments for the construction of larger and flexible molecules. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1038–1047, 2001     

Structure Investigation of Bridgehead Aziridine: Synthesis,Theoretical, and Crystallographic Study of 2,4,6‐Triphenyl‐1,3‐diazabicyclo[3.1.0]hex‐3‐ene

A one‐pot three‐component procedure to efficiently create the 1,3‐diazabicyclo[3.1.0]hex‐3‐ene system is reported. The molecular structure of 2,4,6‐triphenyl‐1,3‐diazabicyclo[3.1.0]hex‐3‐ene ( 3 ) was studied by X‐ray diffraction and compared to ab initio and density‐functional‐theory (DFT) calculations restricted to the core moiety. Geometry optimizations for structural isomers and tautomeric forms of this aziridine fragment, taken as simplified models, were carried out at high calculation levels. Moreover, the same methods were utilized to evaluate the proton affinity of two crucial aziridine tautomers.     

The thioketone–enethiol tautomerism of aliphatic thiocarbonyls: An ab initio study

Approximate minimum energy reaction paths have been calculated for two thioketone–enethiol tautomeric systems using an ab initio SCF–MO method. The calculations indicate nearly equal stabil ties of the isolated tautomers in both systems and an energy barrier of ca. 85 kcal/mol for their interconversion. This barrier is expected to be significantly lower in solution as a result of solvent–solute interactions.