Semiempirical MO methods

Thermodynamic properties such as heats of reaction and heats of formation can be computed mote rehably by ab initio theory than by semiempirical MO methods (55). However, the Hterature of the method appropriate to the study should be carefully checked before a technique is selected. Finally, the role of computer graphics in evaluating quantum mechanical properties should not be overlooked. As seen in Figures 2—6, significant information can be conveyed with stick models or various surfaces with charge properties mapped onto them. Additionally, information about orbitals, such as the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), which ate important sites of reactivity in electrophilic and nucleophilic reactions, can be plotted readily. Figure 7 shows representations of the HOMO and LUMO, respectively, for the antiulcer dmg Zantac. 

Even though molecular mechanics has given satisfactory results (i.e., results that agree with experimental measurements) for many molecules, it is still not totally reliable, since it does fail in certain cases. A further limitation is that it can be used only in cases for which transferable parameters can be obtained from simple molecules. Molecular orbital calculations do not have this limitation, but to some extent semiempirical MO methods do. 

The statistical evaluations of the preceding section indicate that the semiempirical MO methods can predict heats of formation with useful accuracy and at very low computational costs. When comparing with... 

In principle there are three methods of calculation the ab initio molecular orbital (MO) method, the semiempirical MO method, and molecular mechanics. The choice depends on a number of factors such as the size of the molecule, the type of information required, and the budget. Whereas the ab initio method is the most basic and reliable quantum mechanical method,t the time requirement is so... 

Gas-phase nucleophilic substitution reactions of Y-benzyl chlorides and X-phenoxide or X-thiophenoxide nucleophiles have been investigated by using the PM3 semiempirical MO method. The structure of the transition state was examined. The values of the gas-phase Hammett constants px and py are much greater than for the solution reactions, but a theoretical cross-interaction constant pxy (ca —0.60 for both phenoxides and thiophenoxides) agrees well with an experimental value of —0.62 for the thiophenoxide reactions in MeOH at 20 °C. Other work by the same group has involved theoretical studies of competitive gas-phase 5 n2 and E2 reactions of NCCH2CH2CI with HO and An ab initio method at the 6-31-l-G level was... 

Results obtained with semiempirical MO methods have supported595 a mechanism for the pyrolysis of vinylphosphirane to phosphapropyne, in which extrusion of ethylene leads to a vinylphosphinidene intermediate. 

Semiempirical MO methods have been employed to determine the reaction surface for intramolecular bromoetherification reactions. Bromonium ions have not been identified as intermediates instead, the additions involve the formation of a weak olefin/Br+ 7r-complex, which is subsequently captured by a proximate nucleophile196. 

The semiempirical MO method has been used to calculate the ground level splitting of Tm2+(f13) ion in the cubic field CaF2 taking into account a and n interactions. The covalent contribution in the ground level splitting of the Tm2+ ion was found to be nearly 50 percent [32]. 

This chapter is devoted to SCF calculations which represent the overwhelming majority of the reported ab initio calculations. We are not going here to treat general problems of SCF theory which are also inherent in popular semiempirical methods such as PPP and CNDO, These features will be intentionally suppressed. Instead, emphasis will be laid on specific problems of the ab initio SCF approach that are not encountered in semiempirical MO methods and on the progress achieved in solution of these problems in last years. 

The simulations in this study were done using the semiempirical MO method PM3(Stewart, 1989 Stewart, 1989 Stewart, 1991) within the context of the QM/MM coupled potential recently implemented within our lab.(Hartsough and Merz, 1995) A modified version of MOP AC 5.0 (Besler, Merz et al., 1990 Merz and Besler, 1990), was used for the QM calculations and the driver MD program was a customized version of AMBER (Pearlman, Case etal., 1991). The PM3 Hamiltonian was selected because of its superior correlation with experimental heats of formation for the compounds studied herein (Stewart, 1989). From a methodological perspective, AMI (Dewar, Zoebisch et al., 1985), or MNDO (Dewar and Thiel, 1977), or any other LCAO based method could have been used. 

Some of the more widely used semiempirical MO methods in recent years have been the MNDO and AMI approximations developed by Dewar and co-workers [20, 21]. They have been parameterized for calculations on systems containing first row elements and some heavier atoms and their reliability has been extensively documented, both in tests of the parameterization and in applications to real problems. 

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