232Organic Chemistry II
Organic Chemistry, Heterocyclic Chemistry, Organic Synthesis, Structure Determination using Spectroscopic Methods
Synthesis of Porphyrins, Carbaporphyrins and Other Biologically and Medicinally Active Macrocycles. Nature has selected the porphyrin nucleus, generally in metalated form, for a surprising number of functions that include oxygen transportation in mammals (hemoglobin), energy production from molecular oxygen 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 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, benzene, naphthalene, indene, cyclopentadiene, cycloheptatriene, pyridine or pyrazole replacing one or more of the usual pyrrole rings. These studies provide new insights into the nature of aromaticity in these "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), platinum(II), iridium(III) and rhodium(III), 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 that exhibit equally exciting reactivity.
Research from our group has been highlighted on four journal covers (Tetrahedron in 2005, the European Journal of Organic Chemistry in 2007 and Organic & Biomolecular Chemistry in 2013 and 2015) and as a frontispiece for the top ranked journal Angewandte Chemie in 2004. To date, I have published over 220 papers in international research journals and received 23 external grants from NSF, NIH, the Petroleum Research Fund and the Camille and Henry Dreyfus Foundation for a total of over 3 million dollars.
T. D. Lash, “Carbaporphyrins and Related Systems. Synthesis, Characterization, Reactivity and Insights into the Nature of Porphyrinoid Aromaticity” in Handbook of Porphyrin Science - With Applications to Chemistry, Physics, Material Science, Engineering, Biology and Medicine, Ed. K. M. Kadish, K. M. Smith and R. Guilard, World Scientific Publishing, Singapore, 2012, Volume 16, Chapter 74, pp 1-329.
T. D. Lash, “Syntheses of Novel Porphyrinoid Chromophores” in The Porphyrin Handbook, Ed. K. M. Kadish, K. M. Smith and R. Guilard, Academic Press: San Diego, CA, 2000, Volume 2: Heteroporphyrins, Expanded Porphyrins and Related Macrocycles, Chapter 10, pp 125-199.
T. D. Lash, “Synthesis of porphyrins with exocyclic rings from cycloalkenopyrroles” in Advances in Nitrogen Heterocycles, Volume 1, Ed. C. J. Moody, JAI Press Inc., 1995, pp 19-69.
T. D. Lash, “Heteroporphyrins and Carbaporphyrins” in Porphyrins for the 21st Century, Volume 1 – Fundamentals, Ed. P. Brothers and M. Senge, Wiley, 2021, in press.
T. D. Lash, “Dicarbaporphyrins and beyond: the quest for quatyrin”, Invited lecture for the 25th Biennial Congress of the International Society of Heterocyclic Chemistry, Santa Barbara, California, August 23-28, 2015.
My research group has given more than 320 presentations at international, national and regional meetings, including approximately 150 presentations at national meetings of the American Chemical Society.
A. Almejbel and T. D. Lash, “Synthesis of neo-confused porphyrins”, 249th ACS National Meeting, Denver, CO, March 22-26, 2015. Abstracts of Papers, ORGN-520.
L. M. Stateman and T. D. Lash, “Development of a carbatripyrrin strategy for synthesizing carbaporphyrinoid systems”, 249th ACS National Meeting, Denver, CO, March 22-26, 2015. Abstracts of Papers, ORGN-525.
L. M. Stateman and T. D. Lash, “Synthesis of rhodium(III) azuliporphyrins”, 249th ACS National Meeting, Denver, CO, March 22-26, 2015. Abstracts of Papers, CHED-1098.
D. I. AbuSalim and T. D. Lash, “Synthesis of new dicarbaporphyrinoid systems”, 247th ACS National Meeting, Dallas, Texas, March 16-20, 2014. Abstracts of Papers, ORGN-676.
S. C. Fosu and T. D. Lash, “Synthesis of electron-rich benziporphyrin analogs”, 247th ACS National Meeting, Dallas, Texas, March 16-20, 2014. Abstracts of Papers, ORGN-677.