Computational chemistry of the silicon nitride surface. 1. Water,ammonia, and water-ammonia complex

This paper deals with computational modeling of structure and properties of the silicon nitride surface zone using combined computational and real experiments. The computational experiment implies quantum chemical calculations of structure and vibrational spectra of polyatomic clusters. The real experiment suggests measurement and analysis of vibrational spectra. For quantum chemical calculations, semiempirical methods (MNDO and AM1) were chosen. In most calculations, the MNDO/H method was preferred because of the presence of many H-bonds in the surface zone. For verification of calculations, we calculated the structures and vibrational spectra of water and ammonia molecules and the water-ammonia complex and compared the results with experimental and ab initio (extended basis) data; MNDO/H proved to be an optimal method giving reliable results. Russian Peoples' Friendship University. Translated fromZhurnal Strukturnoi Khimii, Vol. 36, No. 1, pp. 58–69, January–February, 1995. Translated by L. Smolina     

Are AM1 ligand‐protein binding enthalpies good enough for use in the rational design of new drugs?

We have examined the performance of semiempirical quantum mechanical methods in solving the problem of accurately predicting protein-ligand binding energies and geometries. Firstly, AM1 and PM3 geometries and binding enthalpies between small molecules that simulate typical ligand-protein interactions were compared with high level quantum mechanical techniques that include electronic correlation (e.g., MP2 or B3LYP). Species studied include alkanes, aromatic systems, molecules including groups with hypervalent sulfur or with donor or acceptor hydrogen bonding capability, as well as ammonium or carboxylate ions. B3LYP/6-311+G(2d,p) binding energies correlated very well with the BSSE corrected MP2/6-31G(d) values. AM1 binding enthalpies also showed good correlation with MP2 values, and their systematic deviation is acceptable when enthalpies are used for the comparison of interaction energies between ligands and a target. PM3 otherwise gave erratic energy differences in comparison to the B3LYP or MP2 approaches. As one would expect, the geometries of the binding complexes showed the known limitations of the semiempirical and DFT methods. AM1 calculations were subsequently applied to a test set consisting of "real" protein active site-ligand complexes. Preliminary results indicate that AM1 could be a valuable tool for the design of new drugs using proteins as templates. This approach also has a reasonable computational cost. The ligand-protein X-ray structures were reasonably reproduced by AM1 calculations and the corresponding AM1 binding enthalpies are in agreement with the results from the "small molecules" test set.     

Computational studies of the structure and cation-anion interactions in 1-ethyl-3-methylimidazolium lactate ionic liquid

Quantum chemical calculations of the structures and cation-anion interaction of 1-ethyl-3-methylimidazolium lactate ([Emim][LAC]) ion pair at the B3LYP/6-31++G** theoretical level were performed. The relevant geometrical characteristics, energy properties, intermolecular H-bonds (H-bonds), and calculated IR vibrations with respect to isolated ions were systematically discussed. The natural bond orbital (NBO) and atoms in molecule (AIM) analyses were also employed to understand the nature of the interactions between cation and anion. The five most stable geometries were verified by analyzing the relative energies and interaction energies. It was found that the most of the C-H···O intermolecular H-bonds interactions in five stable conformers have some covalent character in nature. The elongation and red shift in IR spectrum of C-H bonds which involve in H-bonds is proved by electron transfers from the lone pairs of the carbonyl O atom of [LAC] to the C-H antibonding orbital of the [Emim]+. The interaction modes are more favorable when the carbonyl O atoms of [LAC] interact with the C2-H of the imidazolium ring and the C-H of the ethyl group through the formation of triple H-bonds.     

Structure of guest-host complexes of β-cyclodextrin with arenes: a quantum-chemical study

The structure of β-cyclodextrin (β-CD), as well as the structure and energetics of β-CD-naphthalene, β-CD-fluorene, β-CD-phenanthrene, β-CD-cyclohexane (1:1), and β-CD-naphthalene (2:2) inclusion complexes was studied by the semiempirical MNDO/PM3 method. Calculations of a β-CD-naphthalene-cyclohexane (1:1:1) complex were also performed. The minimum heat of formation was found for the symmetric β-CD conformation withC ₇ symmetry axis. The structure is stabilized by the ring of interunit H-bonds formed by the protons of the 2-OH groups and the O atoms of the 3′-OH groups of the glucose units. Preferableness of this orientation of interunit H-bonds was confirmed byab initio calculations of the molecule of α-(1–4)-glucobiose (maltose) in the MP2/6-31G(d,p)//6-31G(d,p) approximation. The formation of any inclusion compounds of β-CD with arenes is energetically favorable: the complexation energy varies in the range −9 to −12 kcal mol⁻¹. Among complexes with naphthalene, that of composition 2:2 is the most energetically favorable, which is in agreement with experimental data. In this complex, β-CD exists as a dimer of the “head-to-head” type, in which both partners are linked by a system of H-bonds. The structure of the “head-to-head” dimer of β-CD was simulated byab initio calculations of the H-bonded dimer of α-d-glucose in the RHF/6-31G(d,p) approximation. In the dimer, both components are linked by a pair of H-bonds formed by the protons of the 3-OH groups and the O atoms of the, 2-OH groups. The dimerization energies obtained fromab initio and semiempirical MNDO/PM3 and AM1 calculations differ by about 2.5 times (8.6vs 3.2 and 3.8 kcal mol⁻¹, respectively).     

Hydration of small anions: Calculations by the AM1 semiempirical method

The AM1 semiempirical molecular orbital method has been used to calculate successive heats of hydration of small anions, including hydride, hydroxide, and the halogen ions, for cluster sizes up to 11 water molecules surrounding the central anion. Heats of hydration agree with available experimental data to within a few kcal/mol. Structures, however, do not always agree well with available ab initio calculations on clusters with one or two water molecules. The results indicate that the AM1 semiempirical technique applied to finite-sized clusters must be used with caution in understanding how hydration affects the chemical reactions of anions.     

Comparison of AM1 and ab initio calculation of the carbon-carbon bond rotation in ethylene glycol diacetate

The C-C glycol bond rotational energy in ethylene diacetate as a polyester model was compared using the semiempirical method AM1 and an ab initio method with an STO-3G basis set. The results were qualitatively much different depending on the method used. Ab initio calculations showed the expected minima at 180 and near 60 (69.6) degrees dihedral angle with maxima at 0 and 120 degrees. The AM1 rotational curve indicated an apparent minimum at a 90 degree dihedral angle, a shallow, apparent maximum at 180 degrees and an apparent maximum at 0 degrees which could not be confirmed as minima or maxima via frequency calculations. Ethylene diacetate analog compounds with one or two ester oxygens replacing methylene group(s) gave curves with AM1 having the general shape for ethylene diacetate by the ab initio method, indicating a parameterization problem for the otherwise very useful AM1 to correctly handle a compound with only two carbons between the two electronegative oxygen atoms thus rendering this method currently unsuitable for examination of rotational energy barriers of such polyester model compounds.     

Elucidating the intermolecular interactions within a desolvated protein-ligand complex. An experimental and computational study

The first detailed study of the intermolecular hydrogens bonds (H-bonds) within a desolvated, noncovalent protein-ligand complex is reported. Using both experimental and computational methods, the intermolecular H-bonds stabilizing protonated and deprotonated ions of a complex composed of a single chain fragment (scFv) of a monoclonal antibody and its native trisaccharide ligand, alphaGal[alphaAbe] alphaMan (1), are characterized. Using the blackbody infrared radiative dissociation-functional group replacement (BIRD/FGR) technique, three H-bond donor-acceptor pairs within the gaseous (scFv + 1)n+ ions are identified and quantified. Additional sites of interaction on the protein and ligand, for which the binding partner could not be elucidated, are also identified. Comparison of the gas-phase interaction maps with the crystal structure suggests that at least two of the specific H-bonds are conserved upon transfer of the complex from solution to the gas phase by electrospray ionization. However, new (nonspecific) interactions can also form in the gas phase. Notably, the nature and strength of the intermolecular interactions can vary significantly with charge state, and striking differences in the structures of the (scFv + 1)n+ and (scFv + 1)n- ions are evident. Intermolecular H-bonds are also identified from molecular dynamics (MD) simulations performed at the +8 and -8 charge states. Agreement is found for a majority of intermolecular interactions predicted for the (scFv + 1)8+ ion by the MD simulation and BIRD/FGR method; the agreement is less favorable in the case of the (scFv + 1)8- ion. However, both the computational and experimental results point to structural differences between the +8 and -8 ions. The computational results also provide insights into the structural changes that accompany the loss of interfacial waters from the complex.     

A method and program for mass quantum chemical calculations of protein—ligand docking complexes

A new fast computational method for mass calculations of docking complexes by the AM1/PM3 semiempirical methods is proposed. The computation time is shortened by at least an order of magnitude compared to alternative schemes of quantum chemical calculations. The root-mean-square deviation of the AM1 calculated energies of formation of complexes from the results obtained by conventional diagonalization procedure is at most 0.4 kcal mol⁻¹. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 418–420, February, 2008.     

The physicochemical properties of <Emphasis Type="Italic">cis-trans</Emphasis> isomers of substituted epoxycyclohexanes and their molecular complexes with maleic anhydride

AM1, IR, and NMR studies of 1-methoxycarbonyl- and 1-acryloyloxymethyl-3,4-epoxycyclohexanes showed that the ratios between their trans and cis isomers were of 0.60: 0.40 and 0.45: 0.55, respectively. The equatorial forms were most favorable energetically (0.86 and 0.67 mole fractions). The trans-e and cis-e H-complexes of the epoxycyclohexanes with maleic anhydride were obtained; their heats of formation ranged from 0.8 to 3.3 kcal/mol according to AM1 calculations. The participation of the epoxide, carbonyl, and methyl or vinyl group in complex formation gave structures I, III, IIa or IIb, and IV with C-H⋯O (I–III) and C-H⋯π (IV) interactions. The vinyl group was a proton donor in complex II and a proton acceptor in complex IV. The presence of H-bonds in the structures caused the polarization of C=C bonds in 1-acryloyloxymethyl-3,4-epoxycyclohexane and maleic anhydride, which increased their reactivities. Structures IIIb and IV should exhibit the highest reactivity in copolymerization, and complex Ib should exhibit that in oxirane ring opening.     

Comparison of the relative stabilities of polycyclic aryl nitrenium ions and arylmethyl cations: ab initio and semiempirical molecular orbital calculations

Ab initio HF/3-21G calculations predict the stabilities of a series of nitrenium ions to increase in the order, phenyl < 2-naphthyl < 1-naphthyl < 2-fluorenyl. Quantitatively similar results are obtained at the MP/6-31G(d) level for the phenyl and naphthyl systems. The relative stabilities of the nitrenium ions qualitatively parallel those of the corresponding isoconjugate arylmethyl cations but are significantly more sensitive to the nature of the aryl group. Semiempirical AM1 calculations of the same quantities are in reasonable agreement with the ab initio values and are used to extend the comparison to a further 20 polycyclic aromatic derivatives. The relative stabilities of the larger set of nitrenium ions are found to be very precisely linearly related to those of the corresponding arylmethyl cations if allowance is made for the electron donating ability of the aryl group as measured by the charge on the exocyclic carbon atom. A similar but approximate relationship can also be demonstrated in terms of simple perturbational molecular orbital theory.     

An examination of intermolecular and intramolecular hydrogen bonding in biomolecules by AM1 and MNDO/M semiempirical molecular orbital studies

The recent NMDO/M modification and parameterization of the MNDO molecular orbital method has been used to analyze intermolecular hydrogen bonding between amino acids and water, and intramolecular hydrogen bonding in monosaccharides. The results have been compared to AM1 calculations on the same systems. The MNDO/M calculations gave values which were similar to ab initio calculations with respect to the intermolecular interactions, but yielded significantly poorer results for the intramolecular interactions. The AM1 procedure performed better on the intramolecular interactions than the MNDO/M procedure, but frequently provided unfavorable three-centered hydrogen bonding geometries for the intermolecular interactions.     

MM and QM/MM Modeling of Threonyl-tRNA Synthetase: Model Testing and Simulations

Aminoacyl-tRNA synthetases are centrally important enzymes in protein synthesis. We have investigated threonyl-tRNA synthetase from E. coli, complexed with reactants, using molecular mechanics and combined quantum mechanical/molecular mechanical (QM/MM) techniques. These modeling methods have the potential to provide molecular level understanding of enzyme catalytic processes. Modeling of this enzyme presents a number of challenges. The procedure of system preparation and testing is described in detail. For example, the number of metal ions at the active site, and their positions, were investigated. Molecular dynamics simulations suggest that the system is most stable when it contains only one magnesium ion, and the zinc ion is removed. Two different QM/MM methods were tested in models based on the findings of MM molecular dynamics simulations. AM1/CHARMM calculations resulted in unrealistic structures for the phosphates in this system. This is apparently due to an error of AM1. PM3/CHARMM calculations proved to be more suitable for this enzyme system. These results will provide a useful basis for future modeling investigations of the enzyme mechanism and dynamics.     

Computational structural determination and energy landscape analysis of the hepatic carcinogen 2-(acetylamino)fluorene

 2-(Acetylamino)fluorene (AAF), a potent mutagen and a prototypical example of the mutagenic aromatic amines, forms covalent adducts to DNA after metabolic activation in the liver. A benchmark study of AAF is presented using a number of the most widely used molecular mechanics and semiempirical computational methods and models. The results are compared to higher-level quantum calculations and to experimentally obtained crystal structures. Hydrogen bonding between AAF molecules in the crystal phase complicates the direct comparison of gas-phase theoretical calculations with experiment, so Hartree–Fock (HF) and Becke–Perdew (BP) density functional theory (DFT) calculations are used as benchmarks for the semiempirical and molecular mechanics results. Systematic conformer searches and dihedral energy landscapes were carried out for AAF using the SYBYL and MMFF94 molecular mechanics force fields; the AM1, PM3 and MNDO semiempirical quantum mechanics methods; HF using the 3-21G*and 6-31G* basis sets; and DFT using the nonlocal BP functional and double numerical polarization basis sets. MMFF94, AM1, HF and DFT calculations all predict the same planar structures, whereas SYBYL, MNDO and PM3 all predict various nonplanar geometries. The AM1 energy landscape is in substantial agreement with HF and DFT predictions; MMFF94 is qualitatively similar to HF and DFT; and the MNDO, PM3 and SYBYL results are qualitatively different from the HF and DFT results and from each other. These results are attributed to deficiencies in MNDO, PM3 and SYBYL. The MNDO, PM3 and SYBYL models may be unreliable for compounds in which an amide group is immediately adjacent to an aromatic ring. Received: 26 May 2002 / Accepted: 12 December 2002 / Published online: 14 February 2003     

Calculation of trans-hydrogen-bond 13C-15N three-bond and other scalar J-couplings in cooperative peptide models. A density functional theory study

We report B3LYP DFT calculations on peptide models that consider the effects of cooperative interactions with proximate H-bonds and local geometry at the H-bonding site upon trans-H-bond (13)C-(15)N three-bond scalar J-couplings. The calculations predict that cooperative interactions with other H-bonds within a H-bonding chain can significantly increase the magnitude of these couplings. Such increases are due to a combination of the presence of the neighboring H-bonds and the slight increase in C=O distances expected for peptide H-bonds near the centers of H-bonding chains. The energies of H-bonds inferred from H-bonding distances, alone, could be significantly in error if the effects of neighboring H-bonds are ignored.     

First preparation and structural determination of 1,1-disubstituted dibenzo[bc,fg][1,4]silathiapentalene derivatives by x-ray crystallographic analysis and MO calculations

1,1-Dimethyldibenzo[bc,fg][1,4]silathiapentalene ( 1a ) was prepared by treatment of 1,9-bis(methyl-sulfinyl)dibenzothiophene with EtMgBr or of dibenzothiophene with n-butyllithium, and then with dimethyl dichlorosilane. The structure of 4,4-dimethyl-dibenzo[bc,fg][1,4]silathiapentalene 1-oxide ( 2 ), obtained by oxidation of compound 1a with mCPBA, was determined by X-ray crystallographic analysis. The structure of compound 2 determined experimentally was compared to the structure obtained by semiempirical molecular orbital calculations (AM1). The MO calculations of compound 1a and its phenyl analog 1b were also performed by AM1 to evaluate their structures. © 1996 John Wiley & Sons, Inc.     

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.     

Molecular structure and conformational dynamics of 3,12-dichloro-5,14-diphenyl-7,9a,16,18a-tetrazadibenzo[a,l]pentacene-9, 18-dione

The X-ray study of 3,12-dichloro-5,14-diphenyl-7,9a,16,18a-tetrazadibenzo[a,l]pentacene-9,18-dione (1), a model compound for a novel class of thermostable polyheteroarylenes, polyquinoquinazolones, has been carried out. The nonsymmetric flattened structure of the molecule observed is a result of intermolecular interactions. It was established using quantum-chemical calculations by the semiempirical AM1 method that the annelation of the 1,6-dihydropyrimidinone ring by aromatic cycles results in increasing the conformational flexibility of the dihydrocycle due to weakening the conjugation between the carbonyl group and the remaining π-system of the molecule. It was shown by X-ray study and quantum-chemical calculations that protonation of1 results in a substantial change in the molecular structure due to the large contribution of the 1,4-dihydro tautomeric form to the structure of the 1,6-dihydropyrimidinone ring. A tendency for the conformational flexibility of the heterocycle to increase upon protonation was revealed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1970–1978, November, 1997.     

Radical ions and radicals in electron-irradiated acrylates and N-isopropylacrylamide: a quantum chemical study

The semiempirical quantum chemical methods MNDO, AM1 and PM3 were used to investigate the performance of the single excited configuration interaction (SCI) approximation for calculating low energy excitation energies of open-shell systems. Systematic calculations were done for eight radicals formed by reactions of H√, OH√ and e⁻_aq with various acrylates and N-isopropylacrylamide. The calculated electronic spectra show a reasonable correlation with experimental data for both neutral radicals and radical ions. The AM1 as well as the PM3 formalism can be successfully applied to calculate the low energy excited states of these types of open shell systems. The best correlation between experimental and calculated excitation energies was obtained using the PM3 method (correlation coefficient 0.96, overall average error 0.16 eV).     

Comparison of AM1 and PM3 semiempirical to ab initio methods in the study of Diels-Alder reactions of butadiene and cyclopentadiene with cyanoethylenes

Assuming a concerted synchronous mechanism with one transition state of the Diels-Alder reactions, the structures of the transition states and the activation energies for the reactions of butadiene and cyclopentadiene with cyanoethylenes were calculated by AM1 and PM3 semiempirical methods. The structural parameters were compared with those obtained by high level Gaussian calculations, whereas the activation energies were compared both with the ab initio calculations and those obtained experimentally. The structural properties calculated with PM3 methods are in general in better agreement with the ab initio calculations. The low level ab initio calculations are in many cases worse than the semiempirical methods. All predicted activation energies with both semiempirical methods are up to 300% higher than the experimental values. The predicted reactivity is also opposite to the experimental data. Only the very high level Gaussian calculations are in good correlation with experimental results. The predicted selectivity of the reaction is also opposite to the experimental facts. Two explanations are offered for this discrepancy: AM1 and PM3 methods cannot handle the calculation of the concerted Diels-Alder transition states and are not recommended to be used for that purpose, or this Diels-Alder reaction is not concerted but is stepwise.