Tenured and Tenure-Track Faculty

Synthesis of Porphyrins, Carbaporphyrins and Other Biologically and Medicinally Active Macrocycles

Nature has selected the porphyrin nucleus, generally in metallated form, for a surprising number of functions that include oxygen transportation in mammals (hemoglobin), energy production from O2 reduction as part of the respiratory chain (cytochrome oxidase), electron transport/redox (cytochromes), peroxide breakdown (catalase, peroxidases), photosynthesis (chlorophylls) and so on. The versatility of this tetrapyrrolic system stems in part from its intrinsic stability and its ability to form chelates with many different transition metals at varying oxidation levels. Porphyrins also represent an unparalleled family of aromatic macrocycles that formally possess [18]annulene characteristics and as such are the only naturally occurring examples of higher bridged annulene structures. Although the porphyrin system is generally near planar, it can be severely distorted from planarity without significantly sacrificing its aromatic properties. On the other hand, the biological functions of metalloporphyrins are known to be modulated by conformational restrictions within protein environments. Porphyrin and their derivatives are often used as photosensitizers in a type of cancer treatment known as photodynamic tumor therapy (PDT) and have found many other medicinal applications, e.g. in the treatment of age-related macular degeneration. In my laboratory, we are developing new synthetic routes to these important macrocyclic compounds. These projects are directed at the synthesis of true porphyrins and related species with novel spectroscopic and chemical properties.

The major emphasis of our current investigations involves the synthesis of porphyrin analogues with exotic subunits such as azulene or indene replacing one or more of the usual pyrrole rings. These studies provide new insights into the nature of aromaticity in these “[18]annulenes of nature” and have resulted in the discovery of remarkable new chemistry. For instance azuliporphyrins have been shown to readily form stable organometallic derivatives with nickel(II), palladium(II) or platinum(II) salts, whereas copper(II) salts give rise to a regioselective oxidation at the internal carbon. In contrast, benzocarbaporphyrins act as trianionic organometallic ligands, generating stable silver(III) and gold(III) derivatives. Benzocarbaporphyrins also react with ferric chloride in alcohol solvents to give carbaporphyrin ketals with strong long wavelength absorptions that make these structures good candidates as superior photosensitizers for applications in PDT. In addition, carbaporphyrin ketals show some promise in the treatment of leishmaniasis. Another carbaporphyrinoid system synthesized by our research group is oxybenziporphyrin, and this acts as both a dianionic or a trianionic ligand generating palladium(II), platinum(II), copper(III), silver(III) and gold(III) complexes. New methodologies are also being developed to synthesize dicarbaporphyrinoid systems which are likely to exhibit equally exciting reactivity.

Research from our group has been highlighted on two journal covers (Tetrahedron in 2005 and the European Journal of Organic Chemistry in 2007) and as a frontispiece for the top ranked journal Angewandte Chemie in 2004:

University of Exeter (United Kingdom): B.Sc. (Hon.), Chemistry, 1975.

University of Wales, College of Cardiff (UK): Ph.D. (Organic Chemistry), 1979.