Semiempirical AM1 electrostatic potentials and AM1 electrostatic potential derived charges: A comparison with ab initio values

Electrostatic potentials calculated from AM1 wave functions have been compared with ab initio STO-3G values and qualitative agreement has been found. Atomic charges derived from AM1 electrostatic potentials for both experimental and AM1 optimized geometries are of comparable quality with STO-3G potential derived charges. These results suggest that the AM1 electrostatic potential may be useful both in its own right and also for deriving atomic charges for use in molecular dynamics studies.     

Structures and molecular surface electrostatic potentials of high-density C,N, H systems

Tri-s-triazine and two ditetrazolodiazines are known to have unusually high crystal densities (for unsubstituted C, N, H compounds). We have used a nonlocal density functional procedure to compute the geometries and energies of these and three related molecules, and then calculated the ab initio SCF electrostatic potentials on their molecular surfaces. We attribute the high densities to the relatively small molecular volumes and the strong intermolecular attractions arising from highly varying surface potentials. The energy differences of the two ditetrazoles and their diazide tautomers were computed, as well as for the dinitro derivative of one of the former.     

On the molecular electrostatic potentials obtained with CNDO and INDO wave functions

Molecular electrostatic potentials computed with CNDO/2 and INDO wave functions are shown to present systematic differences with respect to ab initio potentials in the case of out-of-plane potentials and in-plane vicinal hetero atoms in planar hetero molecules.     

Ab initioMO investigation of the ethanolamine–formic acid complex

The title complex is considered a model for the interaction of catecholamine-type ligands with anionogenic sites of receptors. It is usually assumed that the ligands interact in the protonated form, but there is no direct evidence of this. Model computations of proton transfer processes should contribute to the elucidation of this important problem. As a first step in this direction we have made computations in the STO-4G base of the interaction energies, molecular electrostatic potentials, the proton potential curves, and the Mulliken population for three different arrangements of the acid and base molecules. Proton potential functions have also been computed for the complexes with two water molecules attached to the acid. The deeper potential well is nearer to the carboxylic oxygen in all cases examined.     

Semiempirical treatment of electrostatic potentials and partial charges in combined quantum mechanical and molecular mechanical approaches

A semiempirical treatment of electrostatic potentials and partial charges is presented. These are the basic components needed for the evaluation of electrostatic interaction energies in combined quantum mechanical and molecular mechanical approaches. The procedure to compute electrostatic potentials uses AM1 and MNDO wave functions and is based on one previously suggested by Ford and Wang. It retains the NDDO approximation and is thus both easy to implement and computationally efficient. Partial atomic charges are derived from a semiempirical charge equilibration model, which is based on the principle of electronegativity equalization. Large sets of ab initio restricted Hartee-Fock (RHF/6-31G*) reference data have been used to calibrate the semiempirical models. Applying the final parameters (C, H, N, O), the ab initio electrostatic potentials are reproduced with an average accuracy of 20% (AM1) and 25% (MNDO), respectively, and the ab initio potential derived charges normally to within 0.1 e. In most cases our parameterized models are more accurate than the much more expensive quasi ab initio techniques, which employ deorthogonalized semiempirical wave functions and have generally been preferred in previous applications. © 1996 John Wiley & Sons, Inc.     

Computed electrostatic potentials and average local ionization energies on the molecular surfaces of some tetracyclines

The electrostatic potentials and average local ionization energies computed on the molecular surfaces of four tetracyclines have been investigated with the objective of identifying common features as well as subtle differences that may be related to their biological activities. The four are the parent molecule tetracycline, chlortetracycline, oxytetracycline, and doxycyline. The calculations were carried out at the HF/STO‐3G*//STO‐3G* level. Our electrostatic potential results show that each molecule has a large negative region that extends along its lower portion, consistent with its ability to complex Ca²⁺ and Mg²⁺ ions. Although the surface electrostatic potentials of the four tetracyclines show many similarities, our statistical measure of local polarity allows us to label doxycycline as the one with the lowest degree of local polarity, consistent with its longer half‐life in vivo. The regions in the tetracyclines with the most reactive electrons are the amide nitrogen lone pairs and certain carbons of the outermost rings. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 82: 160–169, 2001     

Lipase-catalyzed production of short-chain acids terpenyl esters of interest to the food industry

The production of low molecular weight esters as flavor compounds by biotechnological processes has a potential interest for the food industry. The use of natural available substrates and enzymes is an essential part of the process design, because the products may obtain natural label. In this study, direct esterification of citronellol and geraniol with short-chain fatty acids catalyzed by free lipase from Mucor miehei was performed with high yields in n-hexane. The effects of the acid:alcohol ratio on the bioconversion rate of increasing chain length esters was investigated. To reach the optimum yield, substrates and enzyme concentration were determined. The inhibiting effects of acid are strongly attenuated by reducing the quantity of acid and increasing the amount of enzyme in media following the optimum values. Improvements have been made to increase the ester purity. The consumption of excess substrate by adding calculated amounts of acid gives a 10% yield enhancement, and leads to 100% pure terpenyl esters. The first steps to a scale-up application were attempted using a reactor that allowed us to produce ester quantities up to 100 cm³. Separation and purification of the products were treated with success, underlining the lipase stability and efficiency under the conditions of this study. The ability to recover the enzyme, and reusing it in bioconversions, plays a major role in reducing the cost of the overall process.     

An analysis of molecular electrostatic potentials obtained by a local density functional approach

Local density functional theory (DFT –LDA ) has been explored as a tool for obtaining the molecular electrostatic potential V(r), using the code DMol. We have presented and discussed DFT –LDA electrostatic potentials for a representative series of molecules: ethylene, benzene, formamide, cytosine, and 2,3,7,8–tetrachlorodibenzo–p–dioxin. V(r) results obtained with a double numerical plus polarization (DNP ) basis set show the key features that are characteristic of the ab initio potentials of these compounds and suggest that this is a useful approach, especially for large molecules that are difficult to study by ab initio methods.     

Comparative study between ab initio and semiempirical electrostatic potentials on molecular surfaces

The electrostatic potentials of 21 molecules containing different functional groups has been computed at the ab initio RHF/6-31G* level on a series of solvent accessible surfaces and compared with MNDO, AM1, and PM3-derived pontentials. We analyzed in detail the distribution of electrostatic potentials on the surfaces around their maximum and minimum values and found out that consistently MNDO gives results similar to ab initio potentials. The actual values of the MNDO electrostatic potentials show a systematic deviation from the “correct” results, but the pattern of the MEP distribution on the surface is similar to that of the ab initio results. In contrast, PM3 fails in some cases to give even the correct number or distribution of “hot spots” of potential (low MEP) on the surface. AM1 behaves somewhere between these two semiempirical methods. As a conclusion, MNDO would be suggested as the best approach to analyses requiring a fast and efficient mapping of electrostatic potentials on simplified models of molecular surfaces. © 1993 John Wiley & Sons, Inc.     

Synthesis of New Fluorinated Derivatives of Quinolinecarboxylic Acids

Ethyl esters of 1-(7-Z-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbamoyl)-5-X-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids (X = H, F; Z = pyrrolidino-, piperidino-, hexamethylenimino-, morpholino-, thiomorpholino-) have been synthesized by the interaction of quinolone-3-carboxylic acid hydrazides with ethyl esters of 3-ethoxy-2-(polyfluorobenzoyl)acrylic acid . It was shown possible to cyclize intramolecularly the esters obtained with the formation of 1,3,4-oxadiazino[6,5,4-i,j]quinoline derivatives.     

Molecular electrostatic potentials and partial atomic charges from correlated wave functions: Applications to the electronic ground and excited states of 3-methylindole

Procedures have been developed to generate molecular electrostatic potentials based on correlated wave function from ab initio or semiempirical electronic structure programs. A new algorithm for point-wise sampling of the potential is described and used to obtain partial atomic charges via a linear, least squares fit between classical and quantum mechanical electrostatic potentials. The proposed sampling algorithm is efficient and promises to introduce less rotational variance in the potential derived partial charges than algorithms applied previously. Electrostatic potentials and fitted atomic charges from ab initio (HF/6–31G* and MP2/6-31G*) and semiempirical (INDO/S; HF, SECI, and SDCI) wave functions are presented for the electronic ground (S₀) and excited (¹L_b, ¹L_a) states of 3-methylindole. © 1992 by John Wiley & Sons, Inc.     

A convenient synthesis of long-chain 4-substituted benzyloxycarbonyl alkanethiols for the formation of self assembled monolayers on metal substrates

New 4-substituted benzyl esters of 16-mercaptohexadecanoic acid were prepared by developing a practicable synthetic procedure and using readily available staring materials. The compounds synthesized have been characterized by NMR, MS, IR spectra and elemental analysis. The mercapto derivatives are precursors for the formation of self-assembled monolayers on metal substrates. Dedicated to Professor Dr. Manfred Hesse on the occasion of his 70 ^th birthday     

Synthesis of phenyldithioglyoxalic acid and its esters. A route to a-ketodithioacid derivatives

A novel route has been developed for the direct synthesis of the hitherto unknowna-ketodithioacid. Benzaldehyde has been treated with carbon disulphide in the presence of potassium cyanide, thereby making the intermediate carbanion Ph-C(OH)CN to add on to carbon disulphide eventually leading to thea-ketodithioacid. The methyl and ω-carboxypropyl esters of this acid have also been prepared.     

Unusually large reactivity differences in the transformation of cyclopropane lactones to 1‐aminocyclopropane‐1‐phosphonic acids and their carboxylic acid analogues

Starting from a cyclopropane lactone 5 , the synthesis of a 1‐aminocyclopropane‐1‐phosphonic acid derivative 11 is described. The considerable differences in the reactivity of the lactone ring opening in the case of a cyclopropane lactone substituted by a phosphonic acid ester 5 and their carboxylic acid ester analogue 2 toward ammonia or amines have been compared and interpreted by using the map of electrostatic potentials. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:90–96, 2001     

Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethane-phosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I)

Summary The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.     

Synthesis of carborane-containing phosphates by catalytic phosphorylation

The catalytic phosphorylation ofo-carboranylmethanol with different phosphorus acid chlorides has been studied. This method makes it possible to obtain esters of phosphorus acids and esters of the corresponding phosphorus acid chlorides containing carboranylmethyl groups. The catalytic phosphorylation of 1,2-bis(hydroxymethyl)-o-carborane affords both acyclic and cyclic phosphate esters. The structure of the synthesizedo-carborano[1,2-e]-1,3,2-dioxaphosphepane was confirmed by X-ray diffraction analysis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 145–149, January, 1995.     

Nonempirical Atom-Atom Potentials for Main Components of Intermolecular Interaction Energy

Atom-atom potentials representing separate contributions to the nonempirical interaction energy have been derived in the SCF decomposition scheme corrected for basis set superposition error by the counterpoise method. The nontransferable long-range electrostatic multipole and classical induction terms have been evaluated directly from cumulative atomic multipole expansions, whereas the short-range exchange, charge-transfer, and electrostatic penetration contributions have been represented by simplified potentials of the form (β + δR^?1) exp(?δR) fitted to the corresponding ab initio results for 336 dimer configurations formed by HF, H₂O, NH₃, CH₄, CO, and CO₂. The dominant anisotropic character of electrostatic multipole atom-atom potentials and much more isotropic nature of the potentials representing short-range terms is illustrated in the Appendix for head-on interactions in CO ‥ OC and HF ‥ FH dimers.     

Electric-field mapping of some substituted 3-pyridinecarboxylic acid cardiotonics and the possible structure–activity relationships

Four esters of 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acid involving substitutions of methyl, isopropyl, tert-butyl, and phenyl groups at the 2-position, which exhibit varying degrees of cardiotonic activities, have been studied using the electric-field and electrostatic potential mapping techniques. The net charge distributions in the molecules were obtained using the MNDO method. Electric-field mapping has been performed in three-dimension in order to obtain information about the possible structure–activity relationships of these compounds. The results show a prominent electric-field region in the methyl-substituted compound extending from near the oxygen atom O₆ to near the methyl group. This fact and orientation of the electric field in this region, in view of the Erhardt model, may be related to the greater cardiotonic activity of the methyl-substituted molecule in comparison to those of the other molecules of this class. © 1992 John Wiley & Sons, Inc.     

Production of natural fruity aroma by Geotrichum candidum

Based on its aromatic potential, Geotrichum candidum isolated from olive vegetation water was tested for the production of volatile compounds. When G. candidum was cultivated on media with glucose as the carbon source, flavor volatile compounds were produced and accumulated in the broth. Fruity flavoring compounds (pineapple-like) such as esters and alcohols were analyzed by gas chromatography coupled to mass spectrometry, including ethyl esters of acetic acid and butyric acid, methyl-3-butan-1-ol, and methyl-2-propan-1-ol. Their synthesis corresponded to the stationary growth phase of the strain. Production of the volatile compounds reached 9.5 g/L of 2-hexanoic acid ethyl ester and 1.6 g/L of benzaldehyde as the main concentrated molecules. Ethyl alcohol seems to be an intermediate metabolite in this pathway.