Charge calculations in molecular mechanics. IX. A general parameterisation of the scheme for saturated halogen,oxygen and nitrogen compounds

Summary The CHARGE2 program for the calculation of partial atomic charges has been amended to include bond parameters for a number of organic functional groups, including halogens, nitrogen and oxygen. These minor amendments to the original scheme produce dipole moments for the fluoro and chloro compounds which are in complete agreement with the observed values.The less complete data sets for the bromo and iodo compounds are also well reproduced, and the dipole moments of a variety of mixed halo compounds are now in better agreement with experiment than previously.The calculated dipole moments of the saturated nitrogen and oxygen compounds are now in much better agreement than in the original scheme, thus the revised parameterisation may be employed with confidence to predict the electrostatic energies of these compounds.Furthermore, the revised scheme now gives a precise proportionality between the charge on the proton in a CH group and the ¹H chemical shift of the corresponding proton, allowing the general prediction, in principle, of ¹H chemical shifts. In addition, attempts to include variable electronegativity in the effect are described for fluoro compounds.For part VIII see Ref. 1.     

Electrostatic interactions in molecular mechanics (MM2) calculations via PEOE partial charges I. Haloalkanes

The PEOE (partial equalization of orbital electronegativity) procedure has been modified slightly and reparametrized for haloalkanes to calculate partial atomic charges suitable for evaluation of dipole moments and electrostatic energies in conjunction with molecular mechanics (MM2) calculations. Dipole moments of 66 haloalkanes are calculated with an average absolute deviation of 0.14 D from experimental values. The conformational energies of 40 compounds have been calculated and the agreement with experimental data is generally good and compares well with calculations by the IDME (induced dipole moment and energy) method. In addition, carbon and proton charges correlate well with C-1s core binding energies and ¹H-NMR (nuclear magnetic resonance) shifts for halomethanes. The most striking benefit of treating electrostatics through a set of partial charges compared to the standard MM2 bond dipole approach is demonstrated by calculations on 1,4-disubstituted cyclohexanes, for which standard MM2 fails to predict the most stable conformation.     

Class IV charge models: A new semiempirical approach in quantum chemistry

Summary We propose a new criterion for defining partial charges on atoms in molecules, namely that physical observables calculated from those partial charges should be as accurate as possible. We also propose a method to obtain such charges based on a mapping from approximate electronic wave functions. The method is illustrated by parameterizing two new charge models called AM1-CM1A and PM3-CM1P, based on experimental dipole moments and, respectively, on AM1 and PM3 semiempirical electronic wave functions. These charge models yield rms errors of 0.30 and 0.26 D, respectively, in the dipole moments of a set of 195 neutral molecules consisting of 103 molecules containing H, C, N and O, covering variations of multiple common organic functional groups, 68 fluorides, chlorides, bromides and iodides, 15 compounds containing H, C, Si or S, and 9 compounds containing C-S-O or C-N-O linkages. In addition, partial charges computed with this method agree extremely well with high-level ab initio calculations for both neutral compounds and ions. The CM1 charge models provide a more accurate point charge representation of the dipole moment than provided by most previously available partial charges, and they are far less expensive to compute.     

Halogen bonding: a theoretical study based on atomic multipoles derived from quantum theory of atoms in molecules

Atomic multipole moments derived from quantum theory of atoms in molecules are used to study halogen bonds in dihalogens (with general formula YX, in which X refers to the halogen directly interacted with the Lewis base) and some molecules containing C–X group. Multipole expansion is used to calculate the electrostatic potential in a vicinity of halogen atom (which is involved in halogen bonding) in terms of atomic monopole, dipole, and quadrupole moments. In all the cases, the zz component of atomic traceless quadrupole moments (where z axis taken along Y–X or C–X bonds) of the halogens plays a stabilizing role in halogen bond formation. The effects of atomic monopole and dipole moments on the formation of a halogen bond in YX molecules depend on Y and X atoms. In Br₂ and Cl₂, the monopole moment of halogens is zero and has no contribution in electrostatic potential and hence in halogen bonding, while in ClBr, FBr, and FCl it is positive and therefore stabilize the halogen bonds. On the other hand, the negative sign of dipole moment of X in all the YX molecules weakens the corresponding halogen bonds. In the C–X-containing molecules, monopole and dipole moments of X atom are negative and consequently destabilize the halogen bonds. So, in these molecules the quadrupole moment of X atom is the only electrostatic term which strengthens the halogen bonds. In addition, we found good linear correlations between halogen bonds strength and electrostatic potentials calculated from multipole expansion.     

A Series of Isolable Silanoic Thio‐, Seleno‐, and Telluroesters (LSi(X)OR) with Donor‐Supported SiX Double Bonds (L=β‐Diketiminate; X=S,Se, Te)

The first silicon analogues of carbonic (carboxylic) esters, the silanoic thio‐, seleno‐, and tellurosilylesters 3 (Si?S), 4 (Si?Se), and 5 (Si?Te), were prepared and isolated in crystalline form in high yield. These thermally robust compounds are easily accessible by direct reaction of the stable siloxysilylene L(Si:)OSi(H)L′ 2 (L=HC(CMe)₂[N(aryl)₂], L′=CH[(C?CH₂)‐CMe][N(aryl)]₂; aryl=2,6‐iPr₂C₆H₃) with the respective elemental chalcogen. The novel compounds were fully characterized by methods including multinuclear NMR spectroscopy and single‐crystal X‐ray diffraction analysis. Owing to intramolecular N→Si donor–acceptor support of the Si?X moieties (X=S, Se, Te), these compounds have a classical valence‐bond N⁺–Si–X^? resonance betaine structure. At the same time, they also display a relatively strong nonclassical Si?X π‐bonding interaction between the chalcogen lone‐pair electrons (n_π donor orbitals) and two antibonding Si? N orbitals (σ*_π acceptor orbitals mainly located at silicon), which was shown by IR and UV/Vis spectroscopy. Accordingly, the Si?X bonds in the chalcogenoesters are 7.4 ( 3 ), 6.7 ( 4 ), and 6.9 % ( 5 ) shorter than the corresponding Si? X single bonds and, thus, only a little longer than those in electronically less disturbed Si?X systems (“heavier” ketones).     

Geometry optimization and electronic structures of molecules H_3AXAH_3

The geometries of molecules H_3AXAH_3(X=O,S,Se and A=C,Si)have been optimizedusing STO-3G ab initio calculations and gradient method and the results are in good agreement withreported experimental values.From the STO-3G optimized geometries,we have also calculated theelectronic structures of these molecules using 4-31G and 6-31G basis sets to obtain the MO energies.atomic net charges and dipole moments.The ionization potentials calculated by 6-31G basis set are ingood agreement with experimental values.     

Conformational analysis—CXIX : Charge distribution in the molecular mechanics method

The method originally proposed by Smith and Eyring for calculating dipole moments of molecules by taking into account the effect of induction and the polarizability of bonds has been extended from an adjacent-bond to an all-bond procedure.The method is applied to some simple mono- and dihalogen compounds. Total dipole moments are reasonably well calculated. The dipole moments of 1,2-diaxial dihalides are correctly calculated for the first time.     

Molecular polarizability of organic molecules and their complexes: LIV. Molar volumes of polyaryl organoelement compounds in solutions,extrapolated to infinite dilution,and steric structure of the molecules

Molar volumes in various solvents were determined for organic derivatives of silicon, phosphorus, arsenic, sulfur, and tellurium, containing aryl nuclei capable to internal rotation about single bonds between them and bridging groups. Additive analysis of the molar volumes of these compounds showed that the aryl nuclei are acoplanar with respect to the bridging groups. Most probable is a conrotatory mutual orientation of the aromatic rings. Molar volumes were also determined for a series of compounds with two bridging groups, which can serve as models of an extreme case of mutual proximity of aryl ring planes in diaryl systems with one bridging group. A possibility for considerably simplifying the methods for determination of dipole moments and Kerr constants for compounds whose molar volumes can be calculated by our developed additive scheme is demonstrated.     

Parameterization of charge model 3 for AM1, PM3, BLYP,and B3LYP

We have recently developed a new Class IV charge model for calculating partial atomic charges in molecules. The new model, called Charge Model 3 (CM3), was parameterized for calculations on molecules containing H, Li, C, N, O, F, Si, S, P, Cl, and Br by Hartree-Fock theory and by hybrid density functional theory (DFT) based on the modified Perdew-Wang density functional with several basis sets. In the present article we extend CM3 to semiempirical molecular orbital theory, in particular Austin Model 1 (AM1) and Parameterized Model 3 (PM3), and to the popular BLYP and B3LYP DFT and hybrid DFT methods, respectively. For the BLYP extension, we consider the 6-31G(d) basis set, and for the B3LYP extension, we consider three basis sets: 6-31G(d), 6-31+G(d), and MIDI!6D. We begin with the previous CM3 strategy, which involves 34 parameters for 30 pairs of elements. We then refine the model to improve the charges in compounds that contain N and O. This modification, involving two new parameters, leads to improved dipole moments for amides, bifunctional H, C, N, O compounds, aldehydes, ketones, esters, and carboxylic acids; the improvement for compounds not containing N results from obtaining more physical parameters for carbonyl groups when the O=C-N conjugation of amides is addressed in the parameterization. In addition, for the PM3 method, we added an additional parameter to improve dipole moments of compounds that contain bonds between C and N. This additional parameter leads to improved accuracy in the dipole moments of aromatic nitrogen heterocycles with five-membered rings.     

极性分子键角与键偶极矩的关系

研究了基态极性分子的键角和键偶极矩之间的关系。我们采用原子偶极矩校正的Hirshfeld （ADCH）电荷来计算键偶极矩,利用电子的局域函数和键临界点处的局域函数值来分析键的电子结构。通过对IVA族（IVA = C,Si,Ge）、VA族（VA = N,P,As ）、VIA族（VIA = O,S,Se）和VIIA族（VIIA = F,Cl,Br）元素形成的系列共价型基态分子,以及环状基态分子的键角和键偶极矩数据进行分析,发现在键的电子结构类似的情况下,由于键偶极矩的排斥作用,这些分子的键角随键偶极矩的增加而增大。这一发现有助于加深我们对分子几何结构的认识。     

Conformational simulations of aqueous solvated alpha-conotoxin GI and its single disulfide analogues using a polarizable force field model

The solution conformation of alpha-conotoxin GI and its two single disulfide analogues are simulated using a polarizable force field in combination with the molecular fragmentation quantum chemical calculation. The polarizability is explicitly described by allowing the partial charges and fragment dipole moments to be variables, with values coming from the linear-scaling energy-based molecular fragmentation calculations at the B3LYP/6-31G(d) level. In comparison with the full quantum chemical calculations, the fragmentation approaches can yield precise ground-state energies, dipole moments, and static polarizabilities for peptides. The B3LYP/6-31G(d) charges and fragment-centered dipole moments are introduced in calculations of electrostatic terms in both AmberFF03 and OPLS force fields. Our test calculations on the gas-phase glucagon (PDB code: 1gcn) and solvated alpha-conotoxin GI (PDB code: 1not) demonstrate that the present polarization model is capable of describing the structural properties (such as the relative conformational energies, intramolecular hydrogen bonds, and disulfide bonds) with accuracy comparable to some other polarizable force fields (ABEEM/MM and OPLS-PFF) and the quantum mechanics/molecular mechanics (QM/MM) hybrid model. The employment of fragment-centered dipole moments in calculations of dipole-dipole interactions can save computational time in comparison with those polarization models using atom-centered dipole moments without much loss of accuracy. The molecular dynamics simulations using the polarizable force field demonstrate that two single disulfide GI analogues are more flexible and less structured than the native alpha-conotoxin GI, in agreement with NMR experiments. The polarization effect is important in simulations of the folding/unfolding process of solvated proteins.     

Infrared Spectroscopic and dielectrometric investigation of the molecular geometry of isocyanato- and isothiocyanato-silane derivatives

The molecular geometry of compounds of the series (CH₃)_nSi(NCX)_4-n, (where n  0, 1, 2, 3 X  S, O) were investigated with the objective of determining the magnitudes of the SiNC angles. Measurement of the infrared spectra and dipole moments were carried out. The infrared spectra unambiguously suggest linearity, and this is supported by dipole moment calculations. The deviation from linearity observed by electron diffraction is a consequence of shrinkage effects δ(SiNCX) resulting from low frequency, large amplitude vibrations. From the dipole moment values it is concluded that the N—Si—N angle in the di- and trifunctional isothiocyanates is larger than the tetrahedral angle. The structural differences between the silicon and carbon compounds can be attributed to (dp)π bonding in the former.     

A dipole moment study of the conformational properties of diaryl diselenides and related compounds

The electric dipole moments of the diaryl diselenides (RC₆H₄)₂Se₂ (R  H, 4-F, 4-Br, 4-CH₃, 3-F) were measured in benzene solution at 25 and 45°C. The conformations of these compounds were deduced by matching experimental moments with values calculated for a variety of possible conformations. In the dissolved state the diselenides exist at 25°C in fixed “skew” conformations characterized by dihedral angles of 75–106° between the CSeSe planes, corresponding to the conformational energy minima. At 45°C oscillations about the SeSe bonds are excited in the diphenyl and bis(4-methylphenyl) diselenides, whereas the 4-bromophenyl derivative exhibits free rotation. The fluoro compounds have temperature-independent dipole moments, suggesting “rigid conformations” with dihedral angles of 106° (4-F) and 74.4° (3-F). An analysis of the dipole moments at 25 and 45°C obtained for the compounds (RC₆H₄)₂X₂ (R  H, 3-F, 4-F, 4-Br, 4-CH₃; X  S, Se, Te) showed that the conformational properties of these derivatives change on passing from X  S to X  Te. The observed variations are explicable in terms of a decreasing repulsion between the lone electron pairs of the chalcogen atoms on going from the disulfides to the ditellurides and a concomitant reduction of the energy barrier to rotations about the XX bonds.     

Atranes

The dipole moments of the Si(OCH₂CH₂)₃N heterocyclic framework were calculated within the framework of an additive scheme by means of data from x-ray diffraction and conformational analysis of silatranes. The direction of the dipole moment of this fragment coincides with the “experimentally” determined value (from nitrogen to silicon), and its magnitude is ～3 D. The dipole moment of the Si ← N coordinate bond was estimated to be 2.2 D, which corresponds to charge transfer from the nitrogen atom to the silicon atom (to the extent of 0.2 e). These results refute the existing concepts of the exceptionally high polarity of the transannular Si ← N bond in silatranes.     

SCF CI PPP study of the electronic structure of bromo derivatives of isomeric 1,5-, 1,6- and 4,6-benzo[h]naphthyridines

For six isomeric bromo 1,5-, 1,6- and 4,6-benzo[h]naphthyridines (bn) 1–6 and three dibromo derivatives 7–9, the electronic structure, wave number, oscillator strength values and dipole moments have been calculated by SCF CI PPP methods, also using the HMO approximation for comparison purposes. The calculated oscillator strength and wave number values were compared with the experimental data of ultraviolet spectroscopy; also comparison of the ultraviolet spectra of 1–9 with those of unsubstituted bn has been made. Plots of the calculated and observed wave number values of the investigated compounds show good correlation.     

Building molecular charge distributions from fragments: Application to HIV-1 protease inhibitors

Interaction energies are a function of the molecular charge distribution. In previous work, we found that the set of atomic partial charges giving the best agreement with experimental vacuum dipole moments were from density functional theory calculations using an extended basis set. Extension of such computations to larger molecules requires an atomic partial charge calculation beyond present computational resources. A solution to this problem is the calculation of atomic partial charges for segments of the molecule and reassociation of such fragments to yield partial charges for the entire molecule. Various partitions and reassociation methods for five molecules relevant to HIV-1 protease inhibitors are examined. A useful method of reassociation is introduced in which atomic partial charges for a large molecule are computed by fitting to the combined electrostatic potential calculated from the fragment partial charges. As expected, the best sites for partitions are shown to be carbon—carbon rather than carbon—nitrogen bonds. © 1997 by John Wiley & Sons, Inc.     

Analysis of competing bonding parameters. Part 2. The structure of halosilanes and halogermanes (MH4−nXn,n=1–4; M=Si,Ge; X=F,Cl, Br)

A qualitative rationalization of bonding patterns in halosilanes and halogermanes (MH_4−nX_n, n=1–4; M=Si, Ge; X=F, Cl, Br) is presented. Geometrical and bonding properties in these molecules are discussed on the basis of ab initio molecular orbital calculations employing the natural bond orbital population analysis. The results have been compared with data derived previously for halomethanes. Differences in the n-dependence of the M–Cl and M–Br bond lengths for M=C, Si, Ge are explained by a significant reduction in the closed-shell repulsion between the halide atoms. As M gets larger, a continuous decrease in the X–M–X bond angle is observed. Small bond angles (for n=2, 3) are favoured by the p-rich M orbitals in the M–X bonds. They are opposed, however, by the X⋯X repulsion. As M gets larger, the X⋯X separation for a given bond angle increases. A reduction in the X–M–X bond angle is therefore accomplished without overcompensation due to the X⋯X repulsion energy. The variation in the charge density at M as a function of n has been rationalized by differences in the electronegativity of the terminal atoms H and X. Dipole moments have been computed for the molecules in the series. As in the fluoromethanes, a maximum in the dipole moments at n=2 is explained by a combination of geometric and electronic properties unique to the fluoro-compounds. These are, an n-independent charge density at the F sites and a significant decrease in the M–F bond distance as n increases.     

Solvent effect on tautomeric equilibria and dipole moments of some alpha substituted benzoylacetanilides

Based on dipole moment measurements, a study was made of the keto-enol equilibria of five alpha substituted benzoylacetanilide derivatives in two non-polar and one polar solvents at 30°C. The enol mole fractions of the compounds investigated were determined by analysis of their ultraviolet spectra. The same type of study was extended to salicylanilide for its resemblance to the enol tautomer of these compounds. A deduction of the most probable configurations of the keto and enol forms was tentatively made through a comparison between the dipole moments of some suggested configurations for these forms of benzoylacetanilide and those measured in benzene for the alpha methyl benzoylacetanilide and salicylanilide, respectively. These inferred configurations were used to calculate the dipole moments of both tautomers of the other compounds, and consequently, the dipole moment values of their tautomeric mixtures in dioxane and chloroform. A comparison between the dipole moment values of their tautomeric mixtures in dioxane and chloroform. A comparison between the dipole moment values calculated in this way and those measured indicated a solute-solvent interaction with dioxane, which chloroform behaved as a non-interacting solvent.     

Charge calculations in molecular mechanics 7: Application to polar π systems incorporating nitro,cyano, amino,C=S and thio substituents

Summary A previously described method for calculating partial atomic charges in molecules has been applied to a variety of different functional groups with electrons. The charges have been determined by varying the relevant Hückel coulombic and resonance integrals so as to reproduce the experimental dipole moments of known compounds. These include nitro, cyano, mercapto and thiocarbonyl compounds, anilines and a series of heterocyclic ring compounds involving nitrogen, oxygen and sulphur atoms. The calculated dipole moments are in good agreement with experimental values and are a considerable improvement on other calculated values, while requiring only a fraction of the computational time necessary for more rigorous methods. The resulting densities compare favourably with other theoretical (CNDO, MNDO and STO-3G) methods.For part 6, see Ref. 7.