Most-substituted bond hypothesis

Examples of such kinetic treatments were provided by work on chiral 1,1,2,2-tetramethylcyclopropane-d630 and rran -l-ethyl-2-methylcyclopropane146 148. At 350.2 °C, the first substrate approached cis, trans equilibrium with rate constant, and suffered loss of optical activity with a rate constant k The /c, /c, ratio was 1.7 130. The second substituted cyclopropane, at 377.2 °C, exhibited kinetic behavior dictated by kf.ka = 2.0 1. Using steady-state kinetic treatments and the most-substituted-bond hypothesis, these rate constant ratios were calculationally transformed into (cyclization) (rotation) ratios of 11 1 and 0.29 1, ratios different by a factor of 38. 

On the applicability of the most-substituted-bond hypothesis to the photochemistry of cyclopropanes, see B. Scholl and H.-J. Hansen, Helv. Chim. Acta, 69,1936 (1986). 

The second, and major, problem with this hypothesis is the fact that N-substitution with propyl groups can ruin concepts of orderly structure-activity relationships. The most glaring example of this is the activity of N,N-di-(n-propyl)-5,6-ADTN in the DA receptor of the renal artery (28). In this case the electron pair must be oriented normal to the plane of the molecule and should not, by the above reasoning, be active. Empirical calculations reveal that the propyl groups essentially "iock the nitrogen so that it cannot rotate about the C(2)-N bond. Thus, the presence of di-n-propyl groups constitutes a unique feature which must somehow distort the receptor so that... 

The water substitute concept states that the stabilizer replaces the water and forms hydrogen bonds with the protein, like water also does. These bonds maintain the native protein conformation and, in this way, stabilize the protein. The water substitution hypothesis has been confirmed either by spectroscopy studies (FTIR), or by experimental observations that have shown that the most efficient stabilizers are sugars which form strong hydrogen bonds with the protein. Indeed, freeze-dried systems with loss of activity present notably altered IR spectra. 

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