Semiempirical techniques applications

In Pople s career in computational chemistry he was first instrumental in the introduction and dissemination of semiempirical techniques, and contributed to the development of a whole set of successful methods that gained broad acceptance and applications. Here we mention only two of the several major figures in addition to Pople who contributed greatly to the development and spreading of semiempirical methods, Robert G. Parr (Fig. 1.16a) and Michael Dewar (Fig. 1.16b). 

This textbook on the application of ab initio and semiempirical techniques for the analysis of organic reaction mechanisms is designed for chemistry undergraduates. 

Much effort is currently devoted to developing more economical quantum-chemical methods for biopolymers. Semiempirical techniques are very inaccurate (even compared to force fields) for description of molecular interactions [12d,e]. More promising are the Density Functional Theory methods [14]. A high quality DFT method can provide, for some applications, results comparable to those obtained by good quality, traditional ab initio techniques. However, high quality DFT techniques are still costly. Furthermore, no DFT method currently works for dispersion-controlled interactions [12b, 15]... 

The importance of the solid-liquid interface in a host of applications has led to extensive study over the past 50 years. Certainly, the study of the solid-liquid interface is no easier than that of the solid-gas interface, and all the complexities noted in Section VIM are present. The surface structural and spectroscopic techniques presented in Chapter VIII are not generally applicable to liquids (note, however. Ref. 1). There is, perforce, some retreat to phenomenology, empirical rules, and semiempirical models. The central importance of the Young equation is evident even in its modification to treat surface heterogeneity or roughness. ... 

This technique has been applied occasionally to orbital-based methods, where it is called seam searching. The rest of the techniques mentioned in this chapter are applicable to semiempirical, density functional theory (DFT), and ah initio techniques. 

The final application considered in this chapter is chosen to illustrate the application of a QM-MM study of an enzyme reaction that employs an ab initio Hamiltonian in the quantum region [67]. Because of the computational intensity of such calculations there are currently very few examples in the literahire of QM-MM shidies that use a quanhim mechanical technique that is more sopliisticated than a semiempirical method. MuUiolland et al. [67] recently reported a study of part of the reaction catalyzed by citrate synthase (CS) in wliich the quanhim region is treated by Hartree-Fock and MP2 methods [10,51],... 

At the present time, it appears that the applicability of semiempirical methods to the study of carbohydrate chemistry has been neglected. Methods are now available for the non—theoretician to investigate molecular systems, reaction mechanisms, and fundamental physical properties, without the need for any extensive knowledge of theoretical methods. Despite this, most computational studies appear to be limited to the use of molecular mechanics techniques. 

Gerald A. Segal, Semiempirical Methods of Electronic Structure Calculation, Pt. A Techniques, in Modern Theoretical Chemistry, Vol. 7, Plenum, New York, 1977. Mark A. Ratner, John R. Sabin, and Samuel B. Trickey, Applications of Model Hamiltonians to the Electron Dynamics of Organic Charge Transfer Salts in Uncertainty Princ. Found. Quantum Mech., William Charles Price and Seymour S. Chissick, Eds., Wiley, Chichester, 1977. 

A study of the electronic nature of metal clusters is a difficult theoretical and experimental problem. Information on small isolated clusters has been obtained with the field-ion microscope, mass spectrometer, or electron microscope, but other techniques are needed for such studies. The semiempirical MO procedure is applicable to this problem and can provide a great deal of detailed information to compare with experiment concerning the electronic structure of the metal cluster. 

For some enzymes, for example many metalloenzymes, a semiempirical QM/MM treatment is inadequate due to the limitations of the semiempirical methods. In such situations, a more sophisticated level of QM treatment (such as ab initio molecular orbital or density-functional theory) may well be required. An recent example of the application of ab initio QM/MM techniques to an enzyme mechanism is a study of acetyl-CoA enolization in citrate synthase... 

The development of molecular orbital (MO) techniques and their applications to structural and reactivity problems in surface chemistry were improved by density functional theory (DFT) methods. In the case of semiempirical MO methods, symmetry arguments in structural chemistry and reactivity were provided however, DFT has allowed theoretical chemistry to predict accurately the structures of clusters in surfaces and organometallic compounds. 

Before delving into the techniques, a semantic excursion seems necessary. First, computational quantum chemistry as used in this chapter reflects the broader definition, referring to any technique that uses computers to model a chemical system via the Schrodinger equation or some approximation thereof this is a catch-all for every ab initio method, semiempirical scheme, and theoretical model chemistry. (Density functional theory also is included, although it does not stringently satisfy this definition, because it enjoys widespread identification with the ab initio methods.) Molecular mechanics, therefore, is not computational quantum chemistry, but its application to hybrid QM/MM methods will be discussed regardless. 

Segal GA, ed. Semiempirical Methods of Electronic Structure Calculation Part A. Techniques Part B. Applications. New York Plenum, 1977. 

These successes did not go unnoticed by industry. Several pharmaceutical companies (1963-1964) became interested in applications of it-electron theory to biochemistry. While it was admittedly premature, it was felt that quantum chemistry was both the wave of the future and the very matrix for rational drug design. Hiickel energies of cephalosporins could be correlated with their biological activities.While companies were applying some mathematical methods of correlation techniques in quantitative structure-activity relationships (QSAR), it was chiefly the Hiickel theory and various forms of semiempirical quantum mechanics that was using a large share of computer time on the IBM 7094 mainframe in 1966. 

---