NH Tautomerism in the Dimethyl Ester of Bonellin, a Natural Chlorin

Abstract

The NH protons of the chlorins (17,18-dihydroporphyrins) and fully conjugated porphyrins can undergo tautomerization between the four central nitrogens. We have investigated the NH tautomerization process of bonellin dimethyl ester by NMR spectroscopy and molecular modeling. In this natural chlorin derivative, the tautomerization was observed to occur between the two degenerate N21−H, N23−H trans-tautomers. The dynamic 1H NMR measurements showed a coalescence temperature of 297 K for the total tautomeric exchange process (N21−Ha ⇌ N23−Hb). The free energy of activation ΔG297⧧ was calculated to be 14.4 kcal/mol on the basis of the Eyring equation. The two-dimensional 1H and 15N heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) NMR techniques were used to assign the 15N and NH proton resonances at natural abundance. In addition to the strong 15N−1H one-bond correlations, the HSQC spectrum showed weak correlations between the diagonally opposite nitrogen and proton, thus providing clear evidence for the NH tautomeric exchange. These weak correlations arise from the exchange between the NH protons after the refocusing period of the HSQC pulse sequence. The semiempirical molecular modeling methods AM1 and PM3 were used to estimate the energies of the possible tautomers. The AM1 and PM3 methods with an unrestricted Hartree−Fock (UHF) spin-pairing option both favor strongly the chlorin tautomers in which an aromatic 18-atom 18 π-electron delocalization pathway is possible without delocalizing the lone-pair electrons of N24 in the reduced sub-ring. In the proposed tautomerization pathway, the fully aromatic N21−H, N22−H and N22−H, N23−H cis-tautomers were found to be energetically more advantageous than the less aromatic N21−H, N24−H and N23−H, N24−H cis-tautomers. The stepwise tautomerization mechanism is concluded for the proton transfer.