Ab Initio MO Theory Research Articles

Secondary structure formation in N-substituted peptides.

A systematic conformational analysis on several model peptides with N-substituted amino acids was performed on the basis of ab initio MO theory at the HF/6-31G* and HF/3-21G levels with inclusion of solvation effects to study the influence of N-substitution on the formation of typically secondary structural elements, e.g. beta sheets, helices and turns. The conformational flexibility of some structures was examined by means of molecular dynamics simulations in the gas phase and in solution. The results show a restriction of the conformational flexibility of the peptide chain after introduction of an N-substituted amino acid. N-substitution makes beta sheet formation more difficult. Several consecutive N-substituted amino acids in a sequence lead to conformers different from those found on the energy hypersurface of the corresponding N-unsubstituted peptides. There is a strong tendency to form periodically helical conformations, e.g. the polyglycine II or the alpha helix, which can be extended over several N-substituted amino acid residues. As long as 1<--4 hydrogen bond formation remains possible, the major types of beta turns can be formed with a distinct preference for the betaII and betaVIa turns. The betaI turn in particular is considerably destabilized.

Ab initio GB study of chemical intermediates in solution; Ethylenesulfonium ion in hydrolysis of 2-chloroethyl methyl sulfide

Ab initio MO theory including solvent effects has been applied to the structure and reactivity of methyl ethylenesulfonium ion, 1, in aqueous solution as a model of the three-membered cyclic sulfonium intermediate expected in the toxic action of sulfur mustard. The 6-31 + G* geometry optimization of the cyclic sulfonium ion 1 suggested that the ring size of 1 is expanded slightly by solvation. The contour lines map of the interaction energy between 1 and Cl− has a very shallow and wide well at 5–6 Å distance from 1. This is the solvent-separated ion pair, and the contact ion pair was not found between 1 and Cl−. The calculated energy diagrams for the SN2-type reactions of 1 with Cl−, H2O, and OH− that give ring-opened compounds indicated the following: (1) The energy of the 1 + Cl− system is similar to that of chloroethyl methyl sulfide (CEMS, 2), and the interconversion between 1 + Cl− and 2 occurs easily in aqueous solution. The 3-21 + G(*) and 6-31 + G* activation energies for the 2 → 1 + Cl− reaction, 20–22 kcal/mol, agree well with the experimental enthalpy of activation for the hydrolysis of 2. (2) The reaction of 1 with OH− gives a very stable hydroxyl compound, 4, and no transition state was found. (3) The reaction of 1 with H2O gives an unstable addition product that is expected to be converted to 4 with the assistance of another H2O molecule. This mechanism is consistent with that proposed by Bartlett and Swain in their pioneering work on the hydrolysis of sulfur mustard. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:503–510, 1998

The Remarkably Stabilized Trilithiocyclopropenium Ion, C3Li3+, and Its Relatives

The structures and energies of lithiated cyclopropenyl cations and their acyclic isomers (C3H3-nLin+, n = 0−3) have been calculated employing ab initio MO (HF/6-31G*) and density functional theory (DFT, Becke3LYP/6-311+G*) methods. The cyclic isomers (4, 6, 10, and 14) are always favored, but when lithium is substituted sequentially along the C3H3+, C3H2Li+, C3HLi2+, and C3Li3+ series, the acyclic forms (5, 7, 11, 16) become progressively less competitive energetically. A triply bridged c-C3(μ-Li)3+ geometry, 14, was preferred over the classical form 3 by 8.7 kcal/mol. A single lithium substituent results in a very large (67 kcal/mol) stabilization of the cyclopropenyl cation. The favorable effects of further lithium substitution are attenuated but are still large: 48.2 and 40.5 kcal/mol for the second and third replacements, respectively. Comparison with polyamino-substituted cyclopropenyl cations suggest c-C3Li3+ (3 and 14) to be a good candidate for the thermodynamically most stable carbenium ion. The stabilization of the cyclopropenyl cation afforded by the excellent π-donor substituent NH2 (42.8, 33.4, and 23.7 kcal/mol for the first, second and third NH2 groups, respectively) is uniformly lower than the corresponding values for Li substitution. The total stabilization due to two NH2 groups, and a Li (128.2 kcal/mol) is higher than that due to three NH2 groups (99.8 kcal/mol). All the lithiated cyclopropyl radicals are computed to have exceptionally low adiabatic ionization energies (3.2−4.3 eV) and even lower than the ionization energies of the alkali metal atoms Li−Cs (4.0−5.6 eV). The ionization energy of C3Li3• is the lowest (3.18 eV), followed by C3(μ-Li)3• (3.35 eV). The 1H, 6Li, and 13C NMR data of cyclopropenyl cation and its lithium derivatives indicate the carbon, lithium, and hydrogen chemical shifts to increase with increasing lithium substitution on the ring. The computed 1H chemical shifts and the magnetic susceptibility anisotropies as well as the nucleus independent chemical shifts (NICS, based on absolute magnetic shieldings) reveal enhanced aromaticity upon increasing lithium substitution. The B3LYP/6-311+G*-computed vibrational frequencies agree closely with experiment for cyclopropenyl cation and, hence, can be used for the structural characterization of the lithiated and amino species.

Structural and energetic relations between ? turns

A systematic quantum chemical study on the structure and stability of the major types of β-turn structures in peptides and proteins was performed at different levels of ab initio MO theory (MP2/6-31G*, HF/6-31G*, HF/3-21G) considering model turns of the general type Ac(SINGLE BOND)Xaa(SINGLE BOND)Yaa(SINGLE BOND)NHCH3 with the amino acids glycine, l- and d-alanine, aminoisobutyric acid, and l-proline. The influence of correlation effects, zero-point vibration energies, thermal energies, and entropies on the turn formation was examined. Solvent effects on the turn stabilities were estimated employing quantum chemical continuum approaches (Onsager's self-consistent reaction field and Tomasi's polarizable continuum models). The results provide insight into the geometry and stability relations between the various β-turn subtypes. They show some characteristic deviations from the widely accepted standard rotation angles of β turns. The stability order of the β-turn subtypes depends strongly on the amino acid type. Thus, the replacement of l-amino acids in the two conformation-determining turn positions by d- or α,α-disubstituted amino acid residues generally increases the turn formation tendency and can be used to favor distinct β-turn subtypes in peptide and protein design. The β-turn subtype preferences, depending on amino acid structure modifications, can be well illustrated by molecular dynamics simulations in the gas phase and in aqueous solution. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 1415–1430, 1997

Inhibition of thyroid hormone uptake by calcium antagonists of the dihydropyridine class.

A series of substituted 4-phenyl-1,4-dihydropyridines 2a-m was tested for their inhibitory effects on L-triiodothyronine (L-T3) uptake by human HepG2 hepatoma cells. The most potent compounds were the nitro-substituted derivatives 2,6-dimethyl-4-(4'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (2m) and the well-known calcium antagonists nitrendipine (2k) and nifedipine (2j) with an uptake inhibition between 80.5 and 85.8% at an application dose of 10(-5) M. On the basis of a theoretical conformational analysis (ab initio MO theory, molecular mechanics, molecular dynamics) of the dihydropyridine derivatives, a unifying stereochemical concept was derived postulating an angular arrangement of the two rings where the phenyl ring of the calcium antagonists, which corresponds to the outer phenyl ring of the thyroid hormones, is bisecting the dihydropyridine ring as a prerequisite for inhibitory potency. This model includes also inhibitors of the N-phenylanthranilic acid type. The interaction of the calcium antagonists with transthyretin (TTR) is discussed in relation to thyroid hormones. The influence of hydrophobicity was estimated by the experimental determination of the 1-octanol/water partition coefficients.

Organometallic Analogs of the Cyclobutadiene Dication: An Ab Initio MO and Density Functional Study of the Symmetrical Planar and Puckered [WL2(μ-CR)]2 Complexes (L = H, Me, F, OH; R = H, F, Me)

Ab initio MO and density functional theory calculations are reported for tungsten complexes [WL2(μ-CR)]2 (L = H, Me, F, OH; R = H, F, Me). The general perception that these complexes are always planar is contradicted. The effect of ligand L and substituent R on the puckering of four-membered W2C2 ring are studied. With L = H, the ring puckering is in the order of R = F < H < Me. With R = H, the ring puckering is in the order of L = OH ≈ F < Me < H. The puckering of W2C2 ring depends more on the ligand L than on the substituent R. The analogous nature of these complexes to cyclobutadiene dications is also discussed.

Peptides and Peptoids - A Systematic Structure Comparison

A systematic analysis of the conformational space of the basic structure unit of peptoids in comparison to the corresponding peptide unit was performed based on ab initio MO theory and complemented by molecular mechanics (MM) and molecular dynamics (MD) calculations both in the gas phase and in aqueous solution.

The dissociative nature of the radical anion of benzyl chloride. A theoretical MO ab initio approach

The potential energy profile of the benzyl chloride radical anion as a function of the CCl bond distance calculated with ab initio MO theory, 6–31G ∗ level and molecular relaxation shows a purely dissociative behavior, provided that constraints are dictated to the direction of the departing chloride anion. If the departing anion is allowed complete freedom, a minimum in the energy profile is found corresponding to a molecular complex between the benzyl radical and the chloride anion. This behavior differs from that of the chlorobenzene radical anion, which shows a change of the symmetry of the electronic ground state from 2B 1 to 2A 1 on elongating the CCl bond distance.

Peptides and peptoids—A quantum chemical structure comparison

Peptoids represent a very interesting structure alternative to peptides. Based on ab initio MO theory employing the 6-31G* and 3-21G basis sets and considering correlation energy, a systematic structure comparison between the basic structure units of peptoids and peptides is performed. The calculations show three minimum conformations denoted as C7β, αD, and α that do not correspond to conformers on the peptide potential energy hypersurface. The possibility of cis peptide bonds in the peptoids was examined. The solvent influence on the structure was estimated by means of various quantum chemical continuum models. © 1996 John Wiley & Sons, Inc.

Peptides and peptoids-A quantum chemical structure comparison

Peptoids represent a very interesting structure alternative to peptides. Based on ab initio MO theory employing the 6-31G* and 3-21G basis sets and considering correlation energy, a systematic structure comparison between the basic structure units of peptoids and peptides is performed. The calculations show three minimum conformations denoted as C7β, αD, and α that do not correspond to conformers on the peptide potential energy hypersurface. The possibility of cis peptide bonds in the peptoids was examined. The solvent influence on the structure was estimated by means of various quantum chemical continuum models. © 1996 John Wiley & Sons, Inc.

A Theoretical Computation of the Aromaticity of (Benzene)Cr(CO)3 Compared to Benzene Using the Exaltation of Magnetic Susceptibility Criterion and a Comparison of Calculated and Experimental NMR Chemical Shifts in These Compounds

A theoretical calculation of the aromaticity of benzene relative to (benzene)Cr(CO)3 (1) based on the exaltation of magnetic susceptibility criterion was carried out using ab initio MO theory. As others have also found, benzene exhibits a diamagnetic susceptibility exaltation, Λcalc = −15.1 ppm cgs, Λexp = −13.7 ppm cgs, and is aromatic. In contrast, (benzene)Cr(CO)3 (1) has a positive susceptibility exaltation, Λcalc = 12.3 ppm cgs, characteristic of an antiaromatic compound. The validity of susceptibility exaltation as an aromaticity indicator for organometallic compounds was also tested for (cyclobutadiene)Fe(CO)3 (16), which proved to be aromatic (Λcalc = −6.10 ppm cgs). The validity of the calculations was further supported by a comparison of the calculated isotropic susceptibility χav of 1 (−109.3 ppm cgs) with an experimental result (−113 ± 22 ppm cgs). The related NMR calculations for 1 reproduce very well the 13C solid state results of Waugh and also the experimental isotropic upfield shift of ca. 2 ppm seen in the 1H NMR spectra of complex 1 relative to benzene. Contrary to the usual assumptions, the in-plane shieldings of the complexed benzene ring are more important than the perpendicular (ring current) counterparts. As expected, the present theoretical study reproduces very well the experimental geometries, energies, and harmonic frequencies of the purely organic compounds, but there is also very good agreement in the calculated properties of the organometallic compounds, where such data are available for comparison. The present study is based on GIAO, CSGT, and IGAIM NMR calculations performed on the optimized geometry of the most stable conformation at the B3LYP/6-311+G** level for the 12 organic and organometallic compounds needed directly or indirectly for the “group increment” magnetic susceptibility exaltation determinations. The organometallic structures include Cr(CO)6 (10), (ethylene)Cr(CO)5 (11), (1,3-butadiene)Cr(CO)4 (12), (benzene)Cr(CO)3 (1), Fe(CO)5 (13), (ethylene)Fe(CO)4 (14), (1,3-butadiene)Fe(CO)3 (15), and (cyclobutadiene)Fe(CO)3 (16).

Ab initio MO study of the solvent effect on the SN2 reaction of the trimethylsulfonium cation with chloride anion

A recently developed ab initio MO theory including solvent effects has been applied to a typical cation-anion reaction, the SN2 reaction of the trimethylsulfonium cation with the chloride anion. In the gas phase, the trimethylsulfonium and chloride ions are unstabilized, and the reaction is expected to proceed rapidly. In aqueous solution, the reactant ions are largely stabilized, and the reaction has been predicted to be endothermic, with an activation energy of 30–40 kcal/mol. This potential energy profile, which agrees with experimental results, has been well elucidated by differential solvation at several stages of the reaction path. At the transition state of this reaction, the C and H atoms in the transferring CH3 group are almost in a plane that is perpendicular to the Cl(SINGLE BOND)C(SINGLE BOND)S line, reflecting the concerted nature of the reaction. The population analysis has shown that the electrons in the C(SINGLE BOND)S bond are mostly withdrawn by the sulfur atom at the transition state and that the electron transfer from Cl to CH3 occurs after the transition state. The calculated activation energy for the reaction in ethanol is smaller than that in water. This agrees with experiments. © 1996 John Wiley & Sons, Inc.

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.

Theoretical Study of the Reaction of Allylsilanes with Carbonyl Compounds

We have studied the reaction of allylsilanes with aldehydes by applying the ab initio MO theory. It has been shown that the reaction takes place via a transition state involving pentacoordinated silicon species. The oxygen of aldehyde attacks an apical site of the silicon center, while the allyl group departs directly from an equatorial site without causing a pseudorotation. The calculation has shown that the reaction of an allylsilacyclobutane model with formaldehyde has a lower activation barrier than the reaction of allylsilane or methyl-substituted allylsilanes. The barrier height is shown to be correlated well with the angle of coordination of substituents on the silicon center. The reactivity of allylsilanes against nucleophiles is discussed by evaluating the local acidic strength of the reaction site.

What Do Ab Initio Calculations Predict for the Structure of Lithiated Azaenolates of Peptides?

AbstractStructures and conformations of the azaenolate lithium salts of amides (formamide, acetamide, and N‐methylacetamide) and of the dipeptide model N‐formylalaninamide were investigated by means of ab initio MO theory. Four possible structures of the lithiated C‐enolates of acetamide were also included in the study. All structures were calculated at the HF/6‐31+G(d) and MP2(fc)/6‐31 + G(d)/HF/6‐31 + G(d) levels; the lithiated azaenolates of formamide were also investigated at higher theoretical levels (up to MP4(fc)/6‐311 + G(d,p)/MP2(fc)/6‐311 + G(d,p)). For the lithiated azaenolates of all amides investigated, the most stable structure contains a four‐membered ring in which the lithium ion is complexed by the oxygen and nitrogen atoms; the substituents attached to the carbon and nitrogen atoms of the azaenolate are in a cis arrangement. The lithiated azaenolates of acetamide are predicted to be more stable than the corresponding C‐enolates. To simulate solvation, calculations on complexes of the lithiated azaenolates of formamide with up to three molecules dimethyl ether were also performed, and all azaenolates of amides were also reoptimized by ab initio reaction‐field calculations. Both solvation models reduce the preference for lithium‐chelated cis structures. The Ramachandran maps of the dilithiated bis(azaenolate) of N‐formylalaninamide (having cis or trans arrangements of the azaenolate substituents) were scanned by MNDO calculations for conformational accessible regions. Thirteen stable structures were subsequently optimized at the HF/6‐31 + G(d) ab initio level. The global minimum resembles a peptide in C7 conformation, but other conformations, not known for peptides, are close in energy. The structures of dimers of the lithiated azaenolates of N‐methylacetamide and of glycinaldehyde were also calculated. The NMR chemical shielding of carbon, nitrogen, and oxygen atoms in all structures were predicted ab initio by using the gauge‐including atomic orbital (GIAO) method.

Ab initio study of acetonitrile coordinated with metal cations

The complexes of acetonitrile with lithium and sodium cations have been investigated at different levels of ab initio MO theory. The structures of the complexes studied were SCF-optimized at STO-3G, 6-31G and 6-31G ∗∗ levels. The binding energy for the donor-acceptor bonded complexes has been estimated, taking into account the basis set superposition error (BSSE) correction, zero-point vibrations and the MP2 correlation contribution to the binding energy at different levels of ab initio MO theory. The nature of the donor-acceptor bond between acetonitrile molecule and metal cation has been studied.

On the tautomerism of maleimide and phthalimide derivatives

The tautomerism of maleimide and phthalimide and their derivatives was examined by means of ah initio MO theory. The molecular geometry of the various tautomers was completely optimized employing the 6-31G ∗ basis set and the semiempirical AM 1 method, respectively. Correlation energy effects were estimated using the MP2 formalism. The solvent influence on the tautomeric equilibria was considered by means of the quantum chemical PCM formalism within the ab initio MO theory and the Cramer-Truhlar method (C.J. Cramer and D.G. Truhlar, J. Am. Chem. Soc., 113 (1991) 8305) incorporated into the semiempirical AM1 calculations. The results indicate the diketo tautomers of maleimide and phthalimide as the most stable ones both in the gas phase and in solution. The stepwise replacement of the oxygen atoms by nitrogen causes significant changes. Whereas the lactam-lactim tautomerism can still be neglected in all compounds, the amino-imino tautomerism gains considerable importance, in particular in the maleic and phthalic imidine systems, where the amino-imino forms are of comparable stability with the diimino forms.

Theoretical study of hydrogen-bonded formaldehyde complexes

The hydrogen-bonded complexes involving formaldehyde and a series of proton donors of varying strengths, have been investigated at different levels of ab initio MO theory. The structures of the studied complexes were SCF optimized at the 6-31G basis set level. The binding energy was estimated employing basis set superposition correction, zero-point vibrations and MP2 correlation contribution at the different basis set: STO-3G; 6-31G; MP2/6-31G; 6-31G**; MP2/6-31G**; 6-311G(2d, 2p) and MP2/6-311G(2d, 2p). Linear relationships were found of the calculated binding energy with: the calculated shift in the carbonyl stretching frequency, the changes in carbonyl bond length and the optimum value of hydrogen-bond distance; furthermore the calculations confirm a parallel trend between the proton-donor ability and the strength of the hydrogen bond.

On the distance dependence of crystal-field parameters for Pr3+: LnCl3

The distance dependences of the intrinsic parameters Bk have been evaluated using the ab initio molecular-orbital MO theory for the Pr3+-Cl- ion pair at different internuclear distances. The theoretical values for the corresponding power-law exponents are t4=6.0 and t6=6.9. The present result shows much better agreement for the theoretical variations of B4(R) and B6(R) with the experimental data than a previous theoretical calculation. The comparison of the present ion-pair system with the earlier theoretical and recent experimental results for the Pr3+-F/sup /on-pair system shows similar distance dependences of the intrinsic parameters.

Electronic coupling through saturated hydrocarbon bridges

Through-bond (TB) coupling between the chromophores of a series of polynorbornyldienes 1( n ), α,ω-diethynyl[ n]staffanes 2( n ), α,ω-divinyl[ n]staffanes 3( n ), and a series of all-trans, n-alkyl compounds, X-(CH 2) l -X, where X=H 2CC 4( n ), HCC 5( n ), OH 6( n ), SH 7( n ), and planar NH 2 8( n ), have been investigated using ab initio MO theory, with the 3–21G basis set, in the Koopmans' theorem approximation. A natural bond orbital (NBO) analysis of the n-alkyl compounds, 4( n )– 8( n ), shows that much of the variation of the TB electronic coupling among the different series is governed by the self-energy of the chromophore orbitals. This conclusion was surmised from “tuning” experiments in which the chromophore self-energies in the NBO Fock matrix of one system are replaced by those of a different chromophore. Analysis of the TB pathways shows that the tight binding (nearest neighbor) model is grossly inadequate in explaining TB orbital interaction behavior, and that intrabridge interactions that skip over one or more bridge bonds also need to be included for a realistic analysis. In addition, model Hamiltonian matrices, constructed using NBO Fock matrix elements, demonstrate the importance of “retracing” pathways.