AM1 Results Research Articles

COMPUTACIONAL STUDY OF THE ELECTRONIC EFFECTS IN ROTATIONAL BARRIER OF THE N-ARILCARBAMATOS N-CO BOND

Amides are the subject of many particularly important studies, as their properties are of interest to different areas, spanning from biochemistry to material sciences because this functional group is present, for instance, in both natural and artificial polymers such as proteins and polyamides. Amides and their derivatives show, frequently, two different equilibrium geometries, which result from an energetic barrier involved on the N-CO bond rotation. The rotational mechanism is influenced by electronic and steric effects. In this sense, amides and carbamates from aniline are particularly interesting substrates, since those effects can be evaluated through aryl or nitrogen substituents. In this work, the N-arylcarbamates N-CO rotational mechanisms were studied by AM1 semi-empiric and HF/6-31G* ab initio calculation. The conformational analysis showed, as expected, two equilibrium geometries and two maximum energies rotamers (transition states TSsyn and TSanti).The rotational barriers were calculated by the energies differences between transition states and equilibrium geometries. Barriers were estimated at 13-17 kcal.mol-1 by the HF/6-31G* calculation. AM1 results, by the other side, are about 40% from the ab initio ones.

ChemInform Abstract: Activation Parameters for Ring Opening of (Bicyclo(n.1.1)alk-1-yl) methyl Radicals.

Ring opening of the (bicyclo[1.1.1]pent-1-yl)methyl (4), (bicyclo[2.1.1]hex-1-yl)methyl (5) and (bicyclo[3.1.1]hept-1-yl)methyl (6) radicals has been investigated by semiempirical molecular orbital theory MINDO/3 and AM1) and by experiment. Our results indicate that (4) ring-opens extremely rapidly, with an estimated energy barrier of less than 22 kJ mol-1. The higher homologues (5) and (6) rearrange more slowly with barriers of about 42.2 and 46.0 kJ mol-1 respectively. This trend is also observed in the MINDO/3 and AM1 results, with the latter giving the better agreement with experiment.

3D comparative structural study of 6-hydroxy-4-methyl-5,7-dinitrocoumarin using experimental and theoretical approaches

The compound 6-hydroxy-4-methyl-5,7-dinitrocoumarin (2) was synthesized with high yield by the nitration of compound 1. Its molecular structure was determined using X-ray diffractometry and compared with the structure obtained from semiempirical, HF, and B3LYP methods. B3LYP calculations offer the best conformity with X-ray diffractometry for bond lengths and bond angles, whereas AM1 results are significantly close to them and provide the best superimposition with the entire 3D crystal structure.

A quantum chemical study on structure of cocrystal of triphenylphosphine oxide and hydroquinone

The cocrystal of triphenylphosphine oxide (TPPO) with hydroquinone (HQ) (2:3) were studied theoretically with AM1, PM3, MNDO and MINDO/3 semi-empirical methods to elucidate its structure. The bond lengths and angles from theoretical studies of molecule TPPO/HQ (2:3) were found to be as expected. Theoretical results, concerning with intermolecular van der Waals forces in cocrystal, were compared with the previously obtained experimental data. PM3 method were found to be the best fit for selected C–C, C–P and P–O bond lengths and angles. For the hydrogen bond geometry AM1 results were found to be comparable with experimental data.

A quantum chemical study on structure of 1,2-Bis(diphenylphosphinoyl)ethane and hydroquinone cocrystal

The cocrystal of 1,2-Bis(diphenylphosphinoyl)ethane (DPPEO) with hydroquinone (HQ) (1:1) were studied theoretically with MINDO/3, MNDO, PM3 and AM1 semi-empirical methods to elucidate its structure. The bond lengths and angles from theoretical studies of molecule DPPEO/HQ (1:1) were found to be as expected. Theoretical results, concerning with intermolecular van der Waals forces in cocrystal, were compared with the previously obtained experimental data and AM1 results were found to be the best fit for selected C–C, C–P and P–O bond lengths and angles of DPPEO/HQ. For the hydrogen bond geometry AM1 results were found to be comparable with experimental data for the molecule without concerning van der Waals contacts.

Theoretical Study of the Highly Diastereoselective 1,3-Dipolar Cycloaddition of 1,4-Dihydropyridine-Containing Azomethine Ylides to [60]Fullerene (Prato's Reaction)

The 1,3-dipolar cycloaddition of azomethine ylides bearing the biologically active 1,4-dihydropiridine ring to C(60) was investigated by means of quantum mechanical calculations at the semiempirical AM1 and DFT (B3LYP/6-31G) methods. The presence of two chiral centers and one chiral axis in the resulting fulleropyrrolidines leads to four possible [6,6] cycloaddition products. Formation of atropoisomers has also been considered. The transition-state structures were computed for the four different cycloaddition pathways to find out the lowest activation energy stereoisomer. In all cases, a frequency analysis and an IRC calculation were carried out to fully characterize the located transition-state structures. AM1 results and single-point energy calculations at the B3LYP/6-31G//AM1 level for the four transition-state structures yield activation energies values below 5 kcal/mol.

A quantum chemical study on structure of 1,2-bis(diphenylphosphinoyl)ethane and phenol cocrystal

The cocrystal of 1,2-bis(diphenylphosphinoyl)ethane (DPPEO) with phenol (1:1) were studied theoretically with AM1, PM3, MNDO and MINDO/3 semi-empirical methods to elucidate its structure. The bond lengths and angles from theoretical studies of molecule DPPEO/phenol (1:1) were found to be as expected. Theoretical results, concerning with intermolecular van der Waals forces in cocrystal, were compared with the previously obtained experimental data and AM1 results were found to be the best fit for bond lengths and angles of DPPEO/phenol.

Ab Initio Study of Prednisolone, 6 -Fluoroprednisolone, 9 -Fluoroprednisolone, and 6 ,9 -Difluoroprednisolone

A theoretical study of prednisolone, 6α-fluoroprednisolone, 9α-fluoroprednisolone, and 6α,9α-difluoroprednisolone has been performed at the ab initio HF/6-31G, MP2/6-31G, and B3LYP/6-31G levels. Structural information and the electronic features of prednisolone and its derivatives and the synergistic effect of 6α,9α-difluoroprednisolone was examined. Contrary to the AM1 and MNDO results, we found 9α-fluoroprednisolone is more stable than the 6α-fluoroprednisolone. The increased corticosteroid activity of the 6α,9α-difluoroprednisolone is most likely due to electronic effects, mainly related to the receptor binding.

How quickly do knotty molecules lose their energy as they grow?

AbstractThe results of UFF and AM1 calculations for CNH2N hydrocarbon trefoil knots are reported for the range of N from 12 to 59 and used to discuss stabilities of knots and size‐dependent trends in their structural parameters. Other types of molecular knots, including figure‐eight and five‐crossing knots, were identified on MM3 and UFF potential energy surfaces of C30H60 and C50H100. A simple tubular model of molecular knots is discussed and used to identify the minimum size of a knot that has no excess energy due to its topology. Predictions of the tubular model are consistent with UFF and AM1 results. Copyright © 2004 John Wiley & Sons, Ltd.

Computed structures and reaction enthalpies of the rearrangements of certain cyclic hexaalkynes to ortho-arene cyclynes

Density-functional theory (BLYP/6-31G*) and semiempirical theory was used to study compounds related to a strained cyclic hexaalkyne that was postulated by Staab et al. as a trimeric intermediate in the copper-mediated oxidative coupling of 2,2′-diethynylbiphenyl. Among the products of this reaction is an ortho-arene cyclyne. It was found that the hexaalkyne→ ortho-arene cyclyne rearrangement is quite exothermic (ca. 130 kcal/mol). Of the semiempirical methods tested, the AM1 results were closer than PM3 or MNDO to BLYP/6-31G*. For the intermediate, two conformations were found: the expected D 3-symmetric conformation and an unexpected C 2-symmetric conformation. Structures and energies of hexamethyl- and dodecamethyl-substituted analogues of the intermediate and product were also calculated at the AM1 level, in order to test whether steric effects might stabilize the intermediate, relative to the product. It was found that even very sterically crowded products were much more stable than the relevant intermediates. This suggested that the large exothermicity of the hexaalkyne→ ortho-arene cyclyne rearrangement might be used to drive formation of interesting strained products. An example used to illustrate this is the rearrangement of a binaphthyl analogue of Staab's biphenyl intermediate. BLYP and AM1 calculations suggest that the rearrangement of this intermediate would be exothermic by ca. 105–110 kcal/mol, despite strain induced by formation of three [5]helicene moieties in the product.

The performance of the semi-empirical AM1 method on small and nanometre-sized N2O clusters

Large N2O clusters containing up to 177 molecules were simulated using the semiempirical AM1 method. Simulated spectra of different cluster sizes show excellent agreement with experimental spectra. The vibrational band shape of the strong N–N stretching vibration is more strongly influenced by shape and size than that of the N–O stretching vibration. Stabilization energies and spectral band shapes confirm a crystal like structure of N2O clusters generated in supersonic jet expansions. The AM1 results are carefully checked against experiment and high-level ab initio methods. Overall, AM1 reproduces experimental results (structure and vibrational frequencies) and MP2 dissociation energies of small N2O clusters far better than any other quantum mechanical method studied here, although AM1 is not explicitly calibrated for the (N2O)n van der Waals system. The good performance of AM1 allows us to simulate N2O clusters built from hundreds of molecules, a size range neither accessible by ab initio nor by continuum methods.

Ab initio studies of tamoxifen and related compounds

AbstractAn extensive theoretical study of tamoxifen and related compounds has been performed at the ab initio Hartree–Fock (HF)/6‐31G** and B3LYP/6‐31G** levels. The optimized structures are in good agreement with X‐ray data. Theoretical calculations indicate that the ground state energies of cis‐ and trans‐tamoxifen, as well as the energies of the 4‐hydroxytamoxifen isomeric pair, are close, which confirms experimental and AM1 results and suggests nearly equivalent populations of the two isomers under equilibrium conditions. The effects of solvation were calculated with the Onsager model with full geometry optimization. The results indicate that solvation has little effect on the total energies. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

Vibrational study of dialkylphosphonates: di- n-propyl- and di- i-propylphosphonates by semiempirical and ab initio methods

Fourier transform infrared and Fourier transform Raman spectra of n-C 3H 7 and i-C 3H 7 dialkylphosphonates have been obtained. Semiempirical AM1 and the ab initio orbital molecular RHF/6-31G * theories have been used to study the molecular geometry, and the harmonic vibrational spectra with the purpose to assist the experimental assignments of these compounds. An extensive discussion on the assignment of the CC, CO, PO and PO stretching is carried out based on experimental data of compounds which have the propyl and isopropyl groups, as well as comparing the vibrational spectra of propane. Most of the RHF/6-31G * and AM1 results, once applied the appropriate scaling factor, showed an excellent agreement with the experimental wavenumbers. A few calculated frequencies related to CC and CO stretching do not agree well with the experimental trends.

Early stages in the addition to C 60 to form C 60X n, X=H, F, Cl, Br, CH 3, C 4H 9

The study of the early stages of addition to C 60 forming C 60X n has been extended to X=H, F, Cl, Br, CH 3, C 4H 9, using the AM1 Hamiltonian with the program mopac 6.0 and the density functional technique B3LYP/6-31G* with gaussian 98. For X=H, F, the density functional results show greater stability of structures based on addition to hex–hex edges than do the AM1 results. For X=Cl, Br, CH 3, addition can either be on hex–hex edges or across the para positions of C 6 rings for C 60X 2. A combination of hex–hex addition and para addition can occur for C 60X 4, C 60X 6 and C 60X 12. Isomers with only para addition are found for C 60X 4, C 60X 8, C 60X 18 and C 60X 24. For C 60Bu 2, there is greater separation of the tert-butyl groups.

Estudo semi-empírico de ácidos hidroxâmicos: ácido formoidroxâmico e derivados do aleloquímico dimboa

Open chain hydroxamic acid (Hx) can exist as Z and E diastereomers of two tautomers, hydroxamic acid and hydroximic acid. The conformational stability of the formohydroxamic acid isomers evaluated by PM3 compared better to ab initio results from the literature than AM1 results. Structural data of the cyclic Hx 2,4-dihydroxy-7-metoxy-2H-1,4-benzoxazin-3(4 H)-one (DIMBOA) obtained by both semiempirical methods compared well to ab initio results. pKa data from the literature for derivatives of the aldolic isomer of DIMBOA were compared to the stability of the anions resulting from the loss of protons of their phenol and hydroxamic acid groups, determined as the difference in heat of formation between anionic and neutral forms, calculated by AM1 and PM3 methods. Good correlations between theoretical and experimental data were obtained for both semiempirical methods.

Comparison of enzyme polarization of ligands and charge-transfer effects for dihydrofolate reductase using point-charge embeddedab initio quantum mechanical and linear-scaling semiempirical quantum mechanical methods

Using quantum mechanical (QM) methods, we investigated the dependence of a number of factors on the polarization by the enzyme dihydrofolate reductase (DHFR) of its ligands—the substrates, folate and dihydrofolate, and the cofactor NADPH—and evaluated the implications for facilitation of the enzymic reductions. Two quite different levels of QM description of the biomolecular system were used. State-of-the-art ab initio QM calculations of the ligands were performed with the bulk DHFR environment modeled using atom-centered point charges. At the other extreme, semiempirical AM1 QM calculations using the linear-scaling Mozyme formalism incorporated in MOPAC2000 allowed for consistent treatment of the 3000-atom system of both enzyme and bound ligands. The study considered the effects of a number of factors on the polarization, including: (i) different levels of ab initio QM treatment (HF, MP2, DFT) and basis sets; (ii) different sets of molecular mechanics (MM) point charges in representing the bulk enzyme; (iii) inclusion of the bulk enzyme environment as either point charges in the ab initio calculations, or explicitly in the semiempirical calculations; (iv) ab initio QM calculations of substrate and ligand together (combined system) or separately (noncombined system); (v) degree of charge transfer between substrate and cofactor, and, for the semiempirical calculations, between bound ligands and enzyme; (vi) polarization of the enzyme in the semiempirical calculations; (vii) differences in the behavior of folate and dihydrofolate; and (viii) DHFRs from different species (E. coli and human) and different X-ray structure coordinate sets from the same species. Polarization was analyzed mainly by differences in point-charge distributions between gas-phase and bound ligands at the level of complete ligands, subcomponents of ligands (residues), and individual atoms in the pterin and nicotinamide rings involved in the DHFR reactions, but some electron density differences were also calculated. Consistent with our preliminary study (Greatbanks et al., Proteins 1999, 37, 157), and earlier work by Bajorath et al. (Proteins 1991, 9, 217; 11, 263) for noncombined ligand systems, the DFT calculations showed an unrealistically large dipolar character for individual ligands compared with HF and MP2 results and anomalously large charge transfer to folate from NADPH in combined calculations, which were not shown by the HF or AM1 results. The origin of this behavior is in the representation of the gas-phase anions (the substrates are dianionic and NADPH is tetraanioinic), with the point-charge enzyme-embedded calculations showing polarization similar to the HF results. The analysis highlights that successful modeling of the polarization properties depends on accurate representation of both the gas-phase and enzyme-bound electronic structures of the QM region. For both folate and dihydrofolate at the HF and MP2 levels, changes in density from enzyme binding in the region of the reducible bonds (N8C7 for folate, C6N5 for dihydrofolate) is small, with the bulk of the polarization taking place in the N2C2N3 region near the Asp27 (or Glu30) active-site group. Polarization at C7 for folate and C6 for dihydrofolate is negative (i.e., does not favor hydride-ion transfer), whereas the trend at N8 for folate, but not at N5 for dihydrofolate, favors protonation. For the Mozyme results, the substrate pterin-ring polarization trends are similar, and also with negligible charge transfer to NADPH, and only a very small charge transfer to the enzyme. For NADPH, the HF, MP2, and Mozyme results indicate charge polarization on binding to the enzyme at the active carbon (C4) of the nicotinamide ring is favorable for hydride-ion transfer (i.e., slightly more negative), with the active hydrogen (H4) also being more negative for the HF and MP2 results. For all methodologies, the nonactive hydrogen (H4′) becomes significantly more positive, which would reduce its potential for transfer. The Mozyme results show a net loss to the enzyme of ∼0.3 electrons, mostly from NADPH, which is strongly localized in the vicinity of the substrate glutamate and NADPH diphosphate and 3′-phosphate groups. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 788–811, 2000

Ab initio molecular orbital calculations on silica rings

The ab initio molecular orbital 3-21G method was applied to silica rings with two to six tetrahedra per ring. The geometries of the rings and their total electronic energies are compared with previous ab initio, AM1 and PM3 results and with experimental values for amorphous silica. The 3-21G method appears to reproduce with accuracy the experimental results. The semi-empirical PM3 method also gives results that compare favourably with the ab initio calculations and thus is concluded to be suitable for use in calculations on bigger silica clusters.

A semi–empirical study on the electronic structure of ellipticines

Ellipticine and some of its derivatives are organic molecules with intense antitumor activity. In this work we report a semi–empirical study on the electronic structure of ellipticine and some derivatives. Geometrical and spectroscopic aspects were investigated through the use of the well–known PM3 (Parametric Method 3) and ZINDO (Zerner’s Intermediate Neglect of Differential Overlap) methods. Comparing PM3 and previously reported AM1 (Austin Method One) results, we found out that overall PM3 results are better. The ZINDO simulated absorption spectra compare well to the available experimental data. We have observed a very simple correlation between the dipole moment value (DM) and the antitumor activity. These results suggest a way to improve and design new antitumor ellipticine derivatives, as well as, to select promising molecules from untested groups.

The thermodynamic stabilities of tricyclic tetraene C12H12 hydrocarbons

The thermodynamic stabilities and heats of formation of tricyclic C12H12 tetraenes 1–6 as well as of a truncated tetrahedron hydrocarbon isomer 7 were computed by various density functional methods in conjunction with a polarized double-ζ basis set. As the DFT stabilities of 1–7 differ significantly from the MM2, MM3, MM4 and AM1 results, we conclude that these empirical and semiempirical methods are inappropriate to study such polycyclic hydrocarbons. Compound 6 with only endocyclic double bonds, a potential synthetic precursor of 7, is found to be less favorable energetically than the other isomers. Although the Csp3–Csp3 single bonds in 1–6 are rather long (1.601 to 1.620 A) due to a combination of ring strain and hyperconjugation, the small nucleus-independent chemical shift (NICS) values of 1 and 6 confirm the expectation that cyclic electron delocalization is lacking. In contrast, NICS is unusually large in the cage center (–14.6) of 7, but this is due to the cumulative diatropic influence of the four cyclopropane rings.

Critical test of PM3-calculated proton transfer activation energies: a comparison with ab initio and AM1 calculations

Intra- and intermolecular proton transfer activation energies are calculated by means of the semiempirical PM3 method and compared with ab initio results obtained at MP2/6–31G ∗ or MP2/6–31G ∗∗ level. It is shown that corrections for zero-point vibrational energy (ZPVE) and thermal contributions do not affect the correlation between semiempirical and ab initio results. The linear relationship obtained suggests that PM3, in spite of some weaknesses, can be employed with a certain confidence to predict proton transfer activation barriers of large molecules or to obtain semi-quantitative trends for large numbers of interrelated systems. It is also shown that PM3 and AM1 results are of comparable quality for intramolecular proton transfers, whereas PM3 is to be preferred for intermolecular reactions, in particular when water molecules are involved.