Intramolecular catalysis hydrogen bonding

In summary, although subtle conformational differences between the various cycloamyloses and the effect of intramolecular hydrogen bonds on their solution conformations remain to be accurately resolved, overall structural features have been clearly defined. This is particularly advantageous and, in fact, a prerequisite if the cycloamyloses are to be profitably used as models for enzymatic or other catalytic processes. In subsequent sections of this article, various aspects of binding and catalysis will be explained on the basis of the chemical nature and geometrical dimensions of the cycloamylose cavity which is, in fact, their active site. 

In the two examples of buffer catalysis of proton transfer from an intramolecularly hydrogen-bonded acid which have been discussed, it seems reasonably certain that the mechanism in Scheme 7 applies. The reactions are of the first order with respect to the catalyst B and it therefore follows that proton removal from the non-hydrogen-bonded species is rate-limiting k j > 2[B]- If this step consists of diffusion-controlled proton removal from a low concentration intermediate, the value k2 lx 109dm3 moP s-1 will apply for proton transfer to an amine. In the case of proton removal by hydroxide ion from 4-(3-nitrophenylazo)salicylate ion, the reaction was found to be of the first order in hydroxide ion up to the highest concentrations which could be studied (0.003 mol dm-3) with a rate... 

Chemical reactivity and hydrogen bonding 320 Proton-transfer behaviour 321 Intramolecular hydrogen-bond catalysis 344 Enzyme catalysis and hydrogen bonding 354 Chymotrypsin 354 Thermolysin 355 Carboxypeptidase 355 Tyrosyl tRNA synthetase 356 Summary 366 Acknowledgements 367 References 367... 

Intramolecular reactions often differ from their intermolecular counterparts in the exceptionally high rates that are observed and some reactions can occur intramolecularly that are impossible between separate molecules. Because of the importance of intramolecular catalysis, the subject has been reviewed frequently, particularly with reference to its connection with enzymic catalysis (Page, 1973, 1984 Fife, 1975 Jencks, 1975 Kirby, 1980 Fersht, 1985 Menger, 1985). The present coverage is limited to examples of intramolecular catalysis that owe some of their efficiency to intramolecular hydrogen bonding. The role that hydrogen bonds play in enzymic reactions is discussed in Section 5. 

In another estimate (Kirby and Percy, 1989), the carboxyl group in l-methoxymethoxy-8-naphthoic acid and the dimethylammonium group in the l-methoxymethoxy-8-A, A -dimethylnaphthylammonium ion are estimated to lead to rate increases by intramolecular catalysis of < ca. 900 and 1.9 X 10 compared to the value of ca. 1 x 10 calculated for the intramolecular catalytic effect of the carboxyl group in 2-methoxymethoxybenzoic acid. The salicylate ion remains the most efficient leaving group thus far discovered that can take part in hydrogen-bond catalysis of the hydrolysis of acetals. 

The mechanism of hydrolysis of 2-carboxyphenylsulphamic acid (42) might be expected to follow that for the hydrolysis of salicyl sulphate, but actually it is thought to proceed by classic intramolecular acid catalysis rather than by hydrogen-bond catalysis. Evidence for a substantial degree of proton transfer from the carboxyl group in the transition state has been obtained (Hopkins and Williams, 1982). 

The reactions that occur when a substrate is bound to an enzyme can be looked upon as multifunctional intramolecular catalysis within a macro-molecular complex. The purpose of the present section is to illustrate some of the varied and important roles that hydrogen bonds play in this form of intramolecular catalysis. 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

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