Base catalyzed proton exchange rates of a model cyclopeptide in water-dimethylsulphoxide solutions

Proton tranfers on the peptide bond of cyclo-Glycyl-L-Prolyl (PH) were studid at 25°C by DNMR in seven H2O/DMSO mixtures (SH) ranging from pure water to anhydrous DMSO. Two kinetic processes (I) and (II) are observed, catalyzed by the conjugate base of either the solvent (OH-) or of the peptide (P-). Mechanisms (I) and (II) were observed alone in the most or least aqueous solvents, respectively. The rate constant of mechanism I, kI $109 M-1s-1 is nearly constant along the series of solvents, being levelled to its diffusion limit. The backward reaction is made slower by addition of DMSO, so that the pK of the peptide (pKNH) becomes smaller than that of the solvent (pKSH) in the least aqueous mixtures, pKNH=18.3 against pKSH=22 to 33. Rate constants for mechanism (II) increase from pure DMSO (1.81×1O6M-1s-1) to the more aqueous solvents (-5×1O8M-1s-1 when XDMSO=0.35), mainly because of bridging water molecules transferring protons within the acid-base pair PH/P-through a Grotthus mechanism.