Direct meso-Alkynylation of Metalloporphyrins Through Gold Catalysis for Hemoprotein Engineering


  • Part of this work was performed at the Department of Chemistry, California Institute for Quantitative Biosciences (QB3, University of California Berkeley, CA 94720 (USA).). A.N. is grateful for a research fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, NI 1341/1-1). We thank Lars Plate and Charles Hespen for helpful discussions regarding H-NOX protein expression. We thank Prof. Christopher J. Chang (University of California, Berkeley) and Prof. Kim D. Janda for access to the microwave reactors. We are also thankful for the support of Dr. Rita Nichiporuk (University of California, Berkeley) for mass spectrometry and Dr. Laura Pasternack for NMR spectroscopy. This is manuscript no. 23004 from The Scripps Research Institute.


A method was developed for the direct functionalization of metalloporphyrins at the methine protons (meso positions) to yield asymmetric alkynylated derivatives by using gold catalysis and hypervalent iodine reagents. This single-step procedure was applied to b-type heme and the product was incorporated into a gas-sensor heme protein. The terminal alkyne allows fluorophore labeling through copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Hemoproteins with this type of engineered cofactor have several potential applications in labeling and imaging technologies. Additionally, the alkyne provides a handle for modulating porphyrin electron density, which affects cofactor redox potential and ligand affinity. This method will be helpful for investigating the chemistry of natural heme proteins and for designing artificial variants with altered properties and reactivities.