Lipscomb model

Figure 3-51. Lipscomb model of the rearrangement in polyhedral boranes top) with the polyhedral rearrangement of icosahedron/cuboctahedron/icosahedron [122],...

Figure 3-58. (a) The Lipscomb model of the rearrangement in polyhedral boranes [3-86]. (b) An example of icosahedron/cuboctahcdron/icosahedron rearrangement [3-86]. 

Theoretical work by Merz and co-workers" essentially follows the pathway in Scheme 8.7 and finds that the bicarbonate is bound in the Lipscomb model, with the Lindskog structure being an intermediate or transition state on the pathway to the more stable form. More recent theory" has emphasized the importance of H2O and other groups at the active site in facilitating the proton transfer reactions. It should be noted that the theoretical conclusions have changed and evolved with time" and must be viewed accordingly. Two X-ray structures with bicarbonate bound to CA I " and a CA II" mutant have been used to support the Lindskog structure. In simple models, both bidentate and monodentate HCOj" has been observed in Cu(II) complexes," while examples of bidentate Co(III)" and monodentate Ni(II)" coordination are known. These and other models have been reviewed recently." ... 

Kihara20 used a core model in which the Lennard-Jones potential is assumed to hold for the shortest distance between the molecular cores instead of molecular centers. By use of linear, tetrahedral, and other shapes of cores, various molecules can be approximated. Thomaes,41 Rowlinson,35 Hamann, McManamey, and Pearse,14 Atoji and Lipscomb,1 Pitzer,30 and Balescu,4 have used other models of attracting centers and other mathemtical methods, but obtain similar conclusions. The primary effect is to steepen the potential curve so that in terms of inverse powers of the inter-... 

Structural model for conformational changes in ATCase, based on the X-ray crystallographic investigations of Lipscomb and colleagues. Note that substrates are thought to enter through a channel, and allosteric effectors alter channel accessibility. 

Carboxypeptidase A was the first zinc enzyme to yield a three-dimensional structure to the X-ray crystallographic method, and the structure of an enzyme-pseudosubstrate complex provided a model for a precatalytic zinc-carbonyl interaction (Lipscomb etai, 1968). Comparative studies have been performed between carboxypeptidase A and thermolysin based on the results of X-ray crystallographic experiments (Argosetai, 1978 Kesterand Matthews, 1977 Monzingoand Matthews, 1984 Matthews, 1988 Christianson and Lipscomb, 1988b). Models of peptide-metal interaction have recently been utilized in studies of metal ion participation in hydrolysis (see e.g., Schepartz and Breslow, 1987). In these examples a dipole-ion interaction is achieved by virtue of a chelate interaction involving the labile carbonyl and some other Lewis base (e.g.. 

CA has been the snbject of numerous theoretical studies, most of which have centered on differentiating between the Lipscomb and Lindskog mechanisms or on the proton-transfer step. Early studies concentrated on substrate binding and simple models for the active site jqqj, mechanistic studies on model active sites were being published229.254- 268 suggested quite early that active-site water molecules may... 

The two metal atoms make use of hybrid orbitals as indicated, and each of these overlaps a hydrogen orbital that is centered midway between the metals but substantially above the metal-metal axis. For a dimeric species, such as diborane, this is repeated with a second set of orbitals and hydrogen atom symmetrically placed on the opposite side of the metal-metal axis. Examination of this model shows that each of the terminal bonds is a normal 2-electron-2-center bond. Only the bonds between the metal centers are nonconventional. An extensive review of these systems has been given by Lipscomb (69). 

CARBONATO COMPLEXES MODELS FOR CARBONIC ANHYDRASE Lipscomb Pathway (Proton Transfer)... 

Kedderis, G.L., and J.C. Lipscomb. 2001. Application of in vitro biotransformation data and pharmacokinetic modeling to risk assessment. Toxicol. Ind. Health 17(5-10) 315-321. Kershaw T.G., T.W. Clarkson, and P.H. Dhahir. 1980. The relationship between blood levels and dose of methylmercury in man. Arch. Environ. Health 35(l) 28-36. 

These methods appear rather simple, yet they were the starting point of a long evolution. Gilles Klopman, whose research interests at Case-Western Reserve University later turned to modeling bioactive molecules, was the first to use Sandorfy s methods. Kenichi Fukui made extensive use of them in his well-known work on the structures and reactions of saturated hydrocarbons and their derivatives. Fukui added his frontier orbital considerations. Around 1959 the milieu of developments in quantum chemistry contributed to inspire William N. Lipscomb to conceive the extended Hiickel method, which was subsequently implemented by Lawrence L. Lohr and Roald Hoffmann.83 Soon thereafter, John Pople and his coworkers introduced self-consistent field methods based on the zero-differential overlap approximation.815... 

Chang, S. L., Wallar, B. J., Lipscomb, J. D., and Mayo, K. H., 1999, Solution structure of component B from methane monooxygenase derived through heteronuclear NMR and molecular modeling, Biochemistry 38 5799n5812. 

Most clusters, however, caimot be described adequately in terms of two-center, two-electron bonds because the coimectivity of the vertices exceeds the number of valence orbitals that are available for bonding. Early efforts to rationalize such systems, such as Lipscomb s styx approach and Kettle s Topological Equivalent Orbital Method, are described by Mingos and Johnston. In these more difi cult cases, the simple valence-bond picture is inappropriate examples are deltahedral clusters composed of B-H vertices or conical M(CO)3 fragments, both of which usually have only three orbitals available for skeletal bonding. Theoretical models for describing these systems will be discussed in the next section. 

Lyons, C.R., Lovchik, J., Hutt, J., Lipscomb, M.F., Wang, E., Heninger, S., Berliba, L., Garrison, K. (2004). Murine model of pulmonary anthrax kinetics of dissemination, histopa-thology, and mouse strain susceptibility. Infect. Immun. 72 4801-9. 

Hoffman, R., and W. N. Lipscomb (1962). Theory of polyhedral molecules. I. Physical factorization of the secular equation. II. A crystal field model. J. Chem. Phys. 36, 2179-95. 

Empirical Potential Functions. There is one more type of treatment which is properly classified as an empirical model of the H bond. An explicit form is assumed for the potential function associated with the movement of the H atom within the H bond. Nordman and Lipscomb have proposed such a model based upon a Morse function (1521). This proposal will not be explored, however, in favor of the similar and more completely developed potential Junction model of Lippincott and Schroeder (1242, 1815). The potential function is written as a sum of four terms, the first of which has the form... 

The molecular structure, a tetragonal pyramid of boron atoms, and constants were obtained from Hrostowski and Myers (3). The vibrational frequencies were reported by Hrostowski and Pimentel (4). The earlier models of pentaborane were assumed to have a hydrocarbon-like structure of low symmetry by Bauer and Pauling (5), and Pitzer (6). However, the electron diffraction and X-ray data by Hedberg, Jones and Schomaker (7), and Dulmage and Lipscomb (8) revealed an unusual pyramidal structure of C y symmetry. 

The TEC model developed by Teo also has been successfully applied to rationalize the geometries of a large number of cluster compounds. The TEC model combines Lauher s rule with Euler s theorem and adds an adjustable parameter This parameter X is equal to the number of electron pairs present in excess of that predicted by the 18-electron rule. " X has also been interpreted in terms of the number of missing antibonding orbitals. Given a value for X, determined by the shape of the cluster, an equation predicts the electron count for a cluster. Theoretical justification of the parameter X is based largely upon the classical molecular orbital calculations performed by Hoffmann and Lipscomb via the extended Hiickel method on the corresponding polyhedral boron hydride clusters The values... 

The catalytic mechanism of carbonic anhydrase has been investigated by Pullman (1981), Cook et al. (1984), Liang and Lipscomb (1988), Merz et al. (1989) and Jacob et al. (1990), who studied gas-phase models using molecular orbital methods. The special importance of electrostatics in the action of this enzyme has been stressed by several authors in the last two decades (Sawaryn and Sokalski, 1979 Sheridan and Allen, 1981 Ressler, 1982 Krauss and Garmer, 1991 Aqvist and Warshel, 1992, 1993). 

The ability of the quantum chemical approaches to analyze, interpret and rationalize all experimental observations on molecular processes in a unified language based on the primary principles of physics, represents an important asset in the study of biological systems where experimental data has to be obtained in a variety of forms and from many different sources. Taking advantage of this formal and anlytic power of the quantum chemical approaches, Lipscomb and his coworkers studied models of enzymatic mechanisms in chymotrypsin (21) and caboxypeptIdase (22). 

Kedderis, GM. In vitro to in vivo extrapolation of metabolic rate constants for physiologically based pharmacokinetic models. In JC Lipscomb and EV Ohanian, editors Toxicokinetics and Risk Assessment. Informa Healthcare Publishers, New York, 2007. 

Fifth, the PBPK model parameters should be estimated using valid in vivo, in vitro, or in silico methods. The current methods for estimation and analysis of chemical-specific parameters as well as biological input data for PBPK models can be found in Krishnan and Andersen (2007) as well as in Lipscomb and Ohanian... 

Lipscomb, J. C., and Poet, T. S. (2008). In vitro measurements of metabolism for apphcation in pharmacokinetic modeling. Pharmacol Ther 118, 82-103. 

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