Noncovalent Models

Steady-state fluorescence spectra recorded after the addition of the NDI or PM I acceptor to the bisporphyrin tweezer ( rrl = 660 nm), demonstrated substantial quenching (75%) with increasing quantities of the NDI or PM I acceptors. Time-resolved emission spectra recorded in toluene for the complex 26 were biexponential containing a dominant short-lived CS components (80 ps, -95%) attributed to photoinduced ET from donor porphyrin to NDI, and a minor long-lived component (Ins, 5%). The lifetime of the dominant short-lived CS state is increased two- to threefold relative to covalently linked systems under similar conditions of solvent, donor-acceptor distance and thermodynamics [37]. Charge recombination rates from 1.4 to 3.8 x 1()9s 1 were observed, depending on whether the NDI or PM I acceptor was bound within the cavity. 

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In the described examples, the pyridoxamine was covalently attached to the polymer while in most real transaminase enzymes the pyridoxamine coenzyme forms a noncovalent active holoenzyme with the protein (apoenzyme). A new artificial transaminase mimic was developed, in which the pyridoxamine binds noncovalently and reversibly to the polymer. The pyridoxamine attached, for example, to a steroid side chain 99 or 100, together with modified PEI 101 (molecular weight of 60000 and 8.7% dodecyl chains) forms the artificial holoenzyme (Figure 38a). The transamination of pyruvic acid was accelerated 28000-fold with 99 + 101 compared to 10 000 with the covalent pyridoxamine-polymer 98 enzyme mimic. This was due to the fact that the noncovalent system 99 - -101 is more dynamic and therefore can adopt a more suitable geometry for the reaction. The artificial transaminase shows effective rate enhancements in converting the ketoacid into the amino acid, but also the pyridoxamine is converted to pyridoxal. The conversion to pyridoxamine is a necessary step in the catalytic cycle to achieve high turnovers however, this was still not possible with the noncovalent model system. It was observed that the reverse process is very slow and actually in all artificial models so far thermodynamically unfavorable. However, it was possible to use sacrificial amino acids at elevated temperatures (60 °C) that were decarboxy-lated to recycle the pyridoxal 102 to pyridoxamine 100 with modest turnover numbers of 81 (Figure 38b). " ... 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

The correct pairing of half-cystine residues is shown to be dependent upon specific noncovalent bonds 17). With this finding in mind, oxidation of a pair of associating thiols (7 and 2) was chosen as a model reaction. Thiol 7 has the same group as cysteine side chain (HSCH2), 2 being a derivative of cysteamine. 

Initial theoretical studies focused on steps (1) and (2). Several model systems were examined with ab initio calculations.1191 For the reaction of methyl amine with methyl acetate, it was shown that the addition/elimi-nation (through a neutral tetrahedral intermediate) and the direct displacement (through a transition state similar to that shown in Figure 5a) mechanisms for aminolysis had comparable activation barriers. However, in the case of methyl amine addition to phenyl acetate, it was shown that the direct displacement pathway is favored by approximately 5 kcal/mol.1201 Noncovalent stabilization of the direct displacement transition state was therefore the focus of the subsequent catalyst design process. 

The rate constants for micelle-catalyzed reactions, when plotted against surfactant concentration, yield approximately sigmoid-shaped curves. The kinetic model commonly used quantitatively to describe the relationship of rate constant to surfactant, D, concentration assumes that micelles, D , form a noncovalent complex (4a) with substrate, S, before catalysis may take place (Menger and Portnoy, 1967 Cordes and Dunlap, 1969). An alternative model... 

Y. Zhao and D. G. Truhlar, Hybrid Meta Density Functional Theory Methods for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions The MPW1B95 and MPWB1K Models and Comparative Assessments for Hydrogen Bonding and van der Waals Interactions, J. Phys. Chem. A 108 (2004), 6908. 

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