Synthesis of a water-soluble, axial-S-ligated Zn(II) porphyrin and its encapsulation by methylated cyclodextrins

Cytochrome P450 (P450) is the ubiquitous enzyme that contains a heme active site axially coordinated by a thiolate ligand. To mimic the structural feature in aqueous solution, we herein synthesized a water-soluble metalloporphyrin bearing a thiolate ligand on its side chain. A zinc complex of meso-tetraarylporphyrin having three sulfonates and one acetylthio (SAc) pendant moiety (SAc-ZnTPPS) was hydrolyzed in NaOH(aq), causing significant red-shifts of Soret and Q-bands due to axial coordination of the thiolate to Zn(II) (S-ZnTPPS). Encapsulation of S-ZnTPPS by two methylated cyclodextrins (TMe-β-CD) caused a further red-shift, indicating enhanced electron donation from the axial thiolate. Structural analysis of SAc-ZnTPPS before and after hydrolysis was performed by NMR spectroscopy and molecular mechanics (MM) calculation, revealing clear structural change to an axially S-ligated Zn complex in the cavity of two TMe-β-CDs. The molecular design of S-ZnTPPS/TMe-β-CD complex successfully achieved the stable thiolate-metal complex formation, promising to create a novel P450 model that functions in aqueous solution.