Effect on substitution

Steric and Strain Effects on Substitution and Ionization Rates... 

SECTION 5.7 STERIC AND STRAIN EFFECTS ON SUBSTITUTION AND IONIZATION RATES... 

IV, C, 1, d). Second, for both classes of aromatic compounds such values show a surprisingly small dependence on the nature of the attacking reagent, probably indicating the predominant role of the reorganization of the substrate toward a new state represented by structure 63 or 65. FinaUy, it may not be fortuitous that a correspondence is found between structural effects on substitution rates and on ionization constants (Section IV,C, l,a). Bond-making would in fact be the essential analogy between these phenomena [Eqs. (16) and (17)], and... 

Kinetic studies are of little value in attempting to determine the extent of complex formation in the reaction path of electrophilic substitution. The reasons for this have been adequately presented elsewhere29 and the conclusions are that, unless the formation of the complex is rate-determining, the kinetic form is independent of complex formation. Further, the influence of complex formation on reaction rates only comes from the factors which lead in the first place to complex formation, and substituent effects are inadequate for showing the extent of complex formation though when they indicate similar effects on substitution and complex formation they provide evidence that the latter is a pathway of the former. 

Table 17 Steric Effects on Substitution Rates of PtQL(PEt3)2...

Consistent with the proposed intermediate, 48, steric effects on substitution are probably negligible. Rates of substitution of cis- or trans- species do not differ greatly (Ghersetti et al., 1965), e.g. (141)... 

Lanthanides are better cofactors than Ca2+ for the activation of trypsinogen by trypsin. Proteins like calmodulin retain their biochemical activity even after substitution by a lanthanide. This is due to the same degree of conformational changes produced by Ca2+ and Ln3+ ions. But most Ca2+ requiring proteins function less effectively on substitution... 

In this chapter, only a brief description of some of the main elements of REACH is provided, and its effect on substitution discussed. Somewhat simplified, the main elements of REACH are as follows ... 

The effects of bromo and iodo substituents in the major groove of DNA have been investigated using 7-halo-7-deaza-8-aza-adenosine and 5-halo-dU derivatives. The incorporation of bromo or iodo groups onto the purine derivative always gave higher stability compared to dA or 7-deaza-8-aza-adenosine. However, there was little effect on substitution of dU. The N -linked 8-aza-7-deaza-... 

The use of pH variation and isotope effects in transient kinetics can be illustrated with a recent study on dihydrofolate reductase. Analysis by steady-state methods had indicated an apparent p/fa of 8.5 that was assigned to an active site aspartate residue required to stabilize the protonated state of the substrate (59). In addition, it was shown that there was an isotope effect on substitution of NADPD (the deuterated analog) for NADPH at high pH but not at low pH, below the apparent p/fa This somewhat puzzling finding was explained by transient-state kinetic analysis. Hydride transfer, the chemical reaction converting enzyme-bound NADPH and dihydrofolate to NAD+ and tetrahydrofolate, was shown to occur at a rate of approximately 1000 sec at low pH. The rate of reaction decreased with increasing pH with a of 6.5, a value more in line with expectations for an active site aspartate residue. As shown in Fig. 14, there was a threefold reduction in the rate of the chemical reaction with NADPD relative to NADPH. Thus direct measurement of the chemical reaction revealed the full isotope effect. 

---