Transition State Structure of the Solvolytic Hydrolysis of NAD+ †

The transition state structure has been determined for the pH-independent solvolytic hydrolysis of NAD+. The structure is based on kinetic isotope effects (KIEs) measured for NAD+'s labeled in various positions of the ribose ring and in the leaving group nitrogen. The KIEs for reactions performed at 100 °C in 50 mM NaOAc (pH 4.0) were as follows: 1-15N, 1.020 ± 0.007; 1‘-14C, 1.016 ± 0.002; [1-15N,1‘-14C], 1.034 ± 0.002; 1‘-3H, 1.194 ± 0.005; …