Calculated structures and heats of formation of some predicted C,N, O,F molecules

Twelve molecules containing only C, N, O, and F, which are of interest in the context of energetic materials, were found to have true local energy minima at the HF/6-31G^* computational level. Both HF/6-31G^* and MP2/6-31G^* geometries are presented. A density functional procedure was used to find gas phase heats of formation. These are strongly positive for most of the molecules. The nitroso group significantly increases H _o ^f.25C compared to the nitro analogue.     

Some reactive properties of chlorooxirane,a likely carcinogenic metabolite of vinyl chloride

We have carried out a computational study of the reactive properties of chlorooxirane, the metabolically produced epoxide of vinyl chloride that is believed to be a direct-acting carcinogenic form of this molecule. An ab initio SCF-MO procedure (GAUSSIAN 70) was used to compute the energy requirements for stretching the C? Cl and both C? O bonds (S_N 1 reactivity) and to determine the course of the epoxide's possible S_N 2 reactions with ammonia, taken as a model for nucleophilic sites on DNA. The epoxide was assumed to be protonated; both the oxygen- and chloro-protonated forms were considered. At each step along the various reaction pathways, the structure of the system was reoptimized. For the oxygen-protonated epoxide, the C₁? O bond has a significantly lower energy barrier to stretching than does the C₂? O. (The carbon bearing the chlorine is designated C₁.) However, both are very much higher than that of the C? Cl bond in the chloro-protonated form, confirming our earlier finding of the relative weakness of this bond. In the S_N 2 processes involving ammonia, intermediate complexes are formed with both carbons of the oxygen-protonated epoxide, the C₂-complex being the more stable. However, the most stable ammonia complex occurs at C₁ of the chloro-protonated epoxide. Our calculated results, both the energies and also the geometry changes, allow us to propose two possible mechanisms for the formation of the 7-N-(2-oxoethyl) derivative of guanine that has been observed to be the major in vivo DNA alkylation product of vinyl chloride and has been suggested as possibly being responsible for its carcinogenicity. One of these mechanisms is S_N 1 and starts with the chloro-protonated epoxide; the other is S_N 2 and involves the oxygen-protonated form.     

Atomic and molecular energies as functionals of the electrostatic potential

Starting from the Hohenberg–Kohn theorem, atomic and molecular energies have been expressed rigorously as functionals of the electronic electrostatic potential, V_elec(r). Explicit formulations have been derived for the functionals representing the kinetic energy and electronic interaction contributions to the total energies.Acknowledgements. The assistance of Dr. Jane S. Murray is greatly appreciated.Contribution to the Jacopo Tomasi Honorary Issue     

Molecular electrostatic potentials-II: Mechanistic aspects of electrophilic interactions of some five-membered heterocycles

The interactions of furan, pyrrole and N-methyl pyrrole with electrophiles have been investigated by means of the calculated molecular electrostatic potentials, obtained from INDO wave functions, which indicate the most attractive sites and pathways of attack for an approaching electrophile. The very distinct preference of these heterocycles for α-substitution can be interpreted quite satisfactorily in the case of furan if it is assumed that the α-hydrogen moves out of the plane of the molecule, forming a quasi-tetrahedral carbon, as an initial step in the reaction. For pyrrole and N-methyl pyrrole it is found to be necessary to invoke out-of-plane “bending” of the N-H, N-CH₃ and C_α-H_α bonds to explain both the preference for α-substitution, and also the relative selectivities of furan, pyrrole and N-methyl pyrrole. The energies, atomic charges and bond orders of various forms of these heterocycles are also discussed.     

Calculated properties of some possible vinyl chloride metabolites

There is considerable evidence indicating that the carcinogenic action of vinyl chloride involves metabolic conversion to the epoxide (chlorooxirane) as the initial step. In order to learn more about its subsequent behavior, we have computed structures, energies and other properties for two different protonated forms of the epoxide, and also for two possible rearrangement products, chloroacetaldehyde and acetyl chloride. An ab initio SCF -MO procedure (GAUSSIAN 70) was used. Oxygen protonation is found to weaken both C? O bonds, the effect being greater for the bond involving the carbon bearing the chlorine. Chlorine protonation leads to a marked weakening of the C? Cl bond; this suggests a possible loss of HCl, leaving behind a carbonium ion (and possible alkylating agent or rearrangement precursor). Thus, while C? O bond breaking is doubtless an important reaction pathway for chlorooxirane, our results indicate that attention should also be focused upon the C? Cl bond; its rupture may conceivably be a key step in the biological action of vinyl chloride.     

Evaluation of a finite multipole expansion technique for the computation of electrostatic potentials of dibenzo-p-dioxins and related systems

The electrostatic potential V( r ) that the nuclei and electrons of a molecule create in the surrounding space is well established as a guide in the study of molecular reactivity, and particularly, of biological recognition processes. Its rigorous computation is, however, very demanding of computer time for large molecules, such as those of interest in recognition interactions. We have accordingly investigated the use of an approximate finite multicenter multipole expansion technique to determine its applicability for producing reliable electrostatic potentials of dibenzo-p-dioxins and related molecules, with significantly reduced amounts of computer time, at distances of interest in recognition studies. A comparative analysis of the potentials of three dibenzo-p-dioxins and a substituted naphthalene molecule computed using both the multipole expansion technique and Gaussian 82 at the STO-5G level has been carried out. Overall we find that regions of negative and positive V( r ) at 1.75 Å above the molecular plane are very well reproduced by the multipole expansion technique, with up to a 20-fold improvement in computer time.     

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.     

The reaction force constant: an indicator of the synchronicity in double proton transfer reactions

Earlier work, both experimental and computational, has drawn attention to the transition region in a chemical reaction, which includes the traditional transition state but extends along the intrinsic reaction coordinate ξ from perturbed forms of the reactants to perturbed forms of the products. The boundaries of this region are defined by the reaction force F(ξ), which is the negative gradient of the potential energy V(ξ) of the system along ξ. The reaction force constant κ(ξ), the second derivative of V(ξ), is negative throughout the transition region. We have now demonstrated, for a series of twelve double proton transfer processes, that the profile of κ(ξ) in the transition region is an indicator of the synchronicity of the two proton migrations in each case. When they are fully or nearly fully synchronous, κ(ξ) has a single minimum in the transition region. When the migrations are considerably nonsynchronous, κ(ξ) has two minima separated by a local maximum. Such an assessment of the degree of synchronicity cannot readily be made from an examination of the transition state alone, nor it is easily detected in the profiles of V(ξ) and F(ξ).     

A computational analysis of the structural features and reactive behavior of some heterocyclic aromatic N-oxides

An ab initio self-consistent-field molecular orbital analysis of the structural features and reactive behavior of pyridine, pyrazine and some of their N-oxide and nitro derivatives has been carried out. Optimized structures have been computed at the 6-31G^* level, yielding geometries in good agreement with experiment. These structures have been used to compute STO-5G electrostatic potentials and average local ionization energies on the respective molecular surfaces. There is considerable conjugation between the N-oxide groups and the aromatic rings, leading to significant para-quinonoid influence, manifested both in terms of structures and reactive properties. The charge-donor role of the N-oxide group allows the aromatic ring in pyridine N-oxide to be susceptible to electrophiles (at the para position) as well as nucleophiles; however, the rings in the pyrazine oxides are only receptive to the latter. The local ionization energies have permitted predictions of pK_a values for pyrazine N-oxide and p-nitropyridine.