NH tautomerism in the natural chlorin derivatives

NH tautomerism of five Mg-free chlorophyll a and b derivatives 2-6 was stud ied utilizing NMR spectroscopy and molecular modeling. The results from the dynamic NMR measurements of the chlorins revealed that substituent effects contribute crucially to the free energy of activation (Delta G(double dagg er)) in the NH tautomeric processes. An intermediate tautomer for the total tautomeric NH exchange in a chlorin was observed for the first time, when the H-1 NMR spectra of chlorin e(6) TME (3) and rhodin g(7) TME (4) (TME = trimethyl eater) were measured at lower temperatures. The lower energy barr iers (Delta G(1)(double dagger)) obtained for the formation of the intermed iate tautomers of 3 and 4, assigned to the N-22-H, N-24-H trans-tautomer, w ere 10.8 and 10.6 kcal/mol, respectively. The energy barrier (Delta G(2)(do uble dagger) value) for the total tautomeric NH exchange in the five chlori ns was found to vary from 13.6 kcal/mol to values higher than 18 kcal/mol. The lowest Delta G(2)(double dagger) value (13.6 kcal/mol) was obtained for rhodochlorin XV dimethyl ester (2), which was the only chlorophyll derivat ive lacking the C-15 substituent. In the case of chlorins 4 and 5, the ster ic crowding around the methoxycarbonylmethyl group at C-15 raised the Delta G(2)(double dagger) activation free-energy to 17.1 kcal/mol. However, the highest energy barrier with Delta G(2)(double dagger) > 18 kcal/mol was obs erved for the NH exchange of pyropheophorbide a methyl ester (6), possessin g the macrocycle rigidifying isocyclic ring E. Our results demonstrate that the steric strain, arising either from the steric crowding around the bulk y substituent at C-15 or the macrocycle rigidifying isocyclic ring E, slows down the NR tautomeric process. We suggest that deformations in the chlori n skeleton are closely connected to the NH tautomeric exchange and that the exchange occurs by a stepwise proton-transfer mechanism via a hydrogen bri dge.