Redox potentials, calculations computational methods

AMI semi-empirical and B3LYP/6-31G(d)/AMl density functional theory (DFT) computational studies were performed with the purpose of determining which variously substituted 1,3,4-oxadiazoles would participate in Diels-Alder reactions as dienes and under what conditions. Also, bond orders for 1,3,4-oxadiazole and its 2,5-diacetyl, 2,5-dimethyl, 2,5-di(trifluoromethyl), and 2,5-di(methoxycarbonyl) derivatives were calculated <1998JMT153>. The AMI method was also used to evaluate the electronic properties of 2,5-bis[5-(4,5,6,7-tetrahydrobenzo[A thien-2-yl)thien-2-yl]-l,3,4-oxadiazole 8. The experimentally determined redox potentials were compared with the calculated highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) energies. The performance of the available parameters from AMI was verified with other semi-empirical calculations (PM3, MNDO) as well as by ab initio methods <1998CEJ2211>. 

Whilst this Chapter is primarily concerned with the methods of determining the free energies of tautomeric or ionisation equilibria via computer simulation of free energy differences, many of the issues raised relate also to the determination of other molecular properties upon which behaviour of the molecule within the body may depend, such as the redox potential or the partition coefficient.6 In the next section, we shall give a brief explanation of the methods used to calculate these free energy differences -namely the use of a thermodynamic cycle in conjunction with ab initio and free energy perturbation (FEP) methods. This enables an explicit representation of the solvent environment to be used. In depth descriptions of the various simulation protocols, or the accuracy limiting factors of the simulations and methods of validation, have not been included. These are... 

The studies discussed here, have been used to establish the scope and accuracy of the MM-AOM method. The results obtained indicate that combined MM-AOM calculations are potentially a powerful tool for the design of novel compounds with particular spectroscopic properties and for the determination of solution structures. The study involving EPR spectroscopy and MM-AOM calculations, discussed in the next section, was the first example of this approach. Others have been published since and confirm the general applicability of the method. Another, particularly instructive example, which also involves the computation of redox potentials is given in Chapter 11. 

The triangle relation of Equation 13.6 is a strong and most useful constraint for computation. The methods for calculation of pK and redox potentials must be consistent and satisfy Equation 13.6 by construction. Quantum chemistry schemes based on implicit solvent models normally meet this consistency requirement. " For all-atom schemes, this is much harder to achieve. This is ultimately why we decided to compute pK by completely removing the acid proton from solution - rather than transferring it to the solvent, which would be the natural approach in DFTMD.35.36... 

Calculations of electrode potentials for metal complexes in solution and metalloproteins have progressed remarkably with increasing computational power and the greater sophistication of combined quantum/classical models. It is clear that the portion of the problem accessible to quantum methods will continue to expand in the future, revealing even more subtle aspects of the relation of redox thermochemistry to structure, bonding, and solvation. 

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