Sulphonamides conformation

The reaction involves the oxyanion of the alcohol which then undergoes an SNAr attack at the ipso sulphonyl carbon atom of the activated aryl ring. The SNAr process is faster for secondary sulphonamides, than for tertiary ones, i.e., R = H Et > Me Ph. This is attributed to formation of the sulphonamide anion and that this anion adopts a preferred conformation conducive to the S Ar reaction127. Alkyl substituents in the hydroxy alkyl group also increase the rate of the rearrangement reaction127. 

The kinetics of the binding of anions and sulphonamides to carbonic anhydrase have been measured by the stopped-flow technique. The results are consistent with a mechanism involving a pH-dependent equilibrium between two co-ordination forms of the enzyme in which anions selectively combine with the low-pH form of the enzyme whereas sulphonamides combine with the high-pH form. The effect of pH on the anion affinity correlates with the pH dependence of the spectral change associated with the cobalt(n) form of the enzyme. Further evidence on the similarity of the conformations at the active sites of the zinc and cobalt(n) forms of carbonic anhydrase has been provided by spin-labelling. A nitroxide-substituted sulphonamide was used as the spin label and its e.s.r. spectrum was found to be almost identical in the two forms of the enzyme-inhibitor complex. 

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