Department of Chemistry at Illinois State University

Tenured and Tenure-Track Faculty

Lash

Timothy D Lash

Distinguished Professor, Organic Chemistry

Office Address: 306 Science Laboratory Building
Office Phone: (309)438-8554
Office Hours: MWF 9:30-11 a.m.
Email: Contact Timothy Lash (tdlash)
Website: Visit Timothy Lash’s Website
Teaching Schedule:
Course NumberSectionCourse NameTimeRoom NumberCourse Links
CHE230.01Organic Chemistry I M W F 14:00 - 14:50FSA 0133
CHE231.02Organic Chemistry Laboratory I T 09:00 - 11:50SLB 0107
CHE290.010Research in Chemistry   
CHE299.010Independent Honor Study in Chemistry   
CHE490.010Research in Chemistry   
Teaching Interests:
Organic Chemistry, Heterocyclic Chemistry, Organic Synthesis, Structure Determination using Spectroscopic Methods
Research Interests:

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:

 

Education:

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

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

Selected Publications:
D. I. AbuSalim, G. M. Ferrence, T. D. Lash, "Synthesis of an adj-Dicarbaporphyrin and the Formation of an Unprecedented Tripalladium Sandwich Complex," Journal of the American Chemical Society, 2014, 136 (18), 6763-6772. doi:10.1021/ja502795x

R. Li, A. D. Lammer, G. M. Ferrence, T. D. Lash, "Synthesis, Structural Characterization, Aromatic Characteristics and Metalation of Neo-confused Porphyrins, a Newly Discovered Class of Porphyrin Isomers," The Journal of Organic Chemistry, 2014, 79 (9), 4078-4093. doi:10.1021/jo500580e

T. D. Lash, "Metal Complexes of Carbaporphyrinoid Systems," Chemistry - An Asian Journal, 2014.

T. D. Lash, J. A. El-Beck, G. M. Ferrence, "Synthesis, Structural Characterization and Reactivity of Heteroazuliporphyrins," Organic & Biomolecular Chemistry, 2014, 12 (2), 316-329. doi:10.1039/C3OB41992D

D. I. AbuSalim, M. L. Merfeld, T. D. Lash, "Dicarbaporphyrinoid Systems. Synthesis of Oxo-adj-dibenziphlorins," Journal of Organic Chemistry, 2013, 78 (20), 10360-10368. doi:10.1021/jo401756q

D. I. AbuSalim, T. D. Lash, "Relative Stability and Diatropic Character of Carbaporphyrin, Dicarbaporphyrin, Tricarbaporphyrin and Quatyrin Tautomers," Journal of Organic Chemistry, 2013, 78 (22), 11535-11548. doi:10.1021/jo4021198

D. I. AbuSalim, T. D. Lash, "Aromatic Character and Relative Stability of Neo-confused Porphyrin Tautomers and Related Compounds," Organic & Biomolecular Chemistry, 2013, 11 (48), 8306-8323. doi:10.1039/C3OB42063A

T. D. Lash, A. M. Toney, K. M. Castans, G. M. Ferrence, "Synthesis of Benziporphyrins and Heterobenziporphyrins and an Assessment of the Diatropic Characteristics of the Protonated Species," Journal of Organic Chemistry, 2013, 78 (18), 9143-9152. doi:10.1021/jo401365p

A. M. Young, T. D. Lash, "6-Oxopyriphlorins," Organic & Biomolecular Chemistry, 2013, 11 (39), 6841-6848. doi:10.1039/C3OB41506F

R. Li, G. M. Ferrence, T. D. Lash, "Synthesis of a Neo-Confused Porphyrin and an Unusual Dihydroporphyrin Derivative," Chemical Communications, 2013, 49 (68), 7537-7539. doi:10.1039/C3CC44248A

T. D. Lash, K. M. Bergman, "Further Observations on Conformational and Substituent Effects in Acid Catalyzed '3 + 1' Cyclizations of Tripyrranes with Aromatic Dialdehydes," The Journal of Organic Chemistry, 2012, 77 (21), 9774-9783. doi:10.1021/jo301945f

T. D. Lash, K. Pokharel, M. Zeller, G. M. Ferrence, "Iridium (III) Azuliporphyrins," Chemical Communications, 2012, 48 (96), 11793-11795. doi:10.1039/C2CC37104A

T. D. Lash, A. D. Lammer, G. M. Ferrence, "Two-Step Synthesis of Stable Dioxadicarbaporphyrins from Bis(3-indenyl)methane," Angewandte Chemie, 2012, 124 (43), 11029-11033. doi:10.1002/ange.201206385
Angewandte Chemie International Edition, 2012, 51 (43), 10871-10875. doi:10.1002/anie.201206385

T. D. Lash, "74. Carbaporphyrins and Related Systems. Synthesis, Characterization, Reactivity and Insights into Porphyrinoid Aromaticity," in Handbook of Porphyrin Science - With Applications to Chemistry, Physics, Material Science, Engineering, Biology and Medicine, (Eds. K. M. Kadish, K. M. Smith, R. Guilard), 2012, 16, 1-329. doi:10.1142/9789814335508_0001

T. D. Lash, A. D. Lammer, A. S. Idate, D. A. Colby, K. White, "Preparation of Azulene-Derived Fulvenedialdehydes and Their Application to the Synthesis of Stable adj-Dicarbaporphyrinoids," Journal of Organic Chemistry, 2012, 77 (5), 2368-2381. doi:10.1021/jo2026977

T. D. Lash, "Carbaporphyrins, Porphyrin Isomers and the Legacy of Emanuel Vogel," Journal of Porphyrins and Phthalocyanines, 2012, 16 (5-6), 423-433. doi:10.1142/S1088424612300017

J. D. Hooker, V. H. Nguyen, V. M. Taylor, D. L. Cedeño, T. D. Lash, M. A. Jones, S. M. Robledo, I. D. Vélez, “New Application for Expanded Porphyrins: Sapphyrin and Heterosapphyrins as Inhibitors of Leishmania Parasites,” Photochemistry and Photobiology, 2012, 88 (1), 194-200. doi:10.1111/j.1751-1097.2011.01034.x

T. D. Lash, "Origin of Aromatic Character in Porphyrinoid Systems," Journal of Porphyrins and Phthalocyanines, 2011, 15 (11-12), 1093-1115. doi:10.1142/S1088424611004063

T. D. Lash, A. D. Lammer, G. M. Ferrence, "Neo-Confused Porphyrins, a New Class of Porphyrin Isomers," Angewandte Chemie, 2011, 123 (41), 9892-9895; Angewandte Chemie International Edition, 2011, 50 (41), 9718-9721. doi:10.1002/ange.201104826

T. D. Lash, K. Miyake, L. Xu, G. M. Ferrence, "Synthesis of a Series of Aromatic Benziporphyrins and Heteroanalogues via Tripyrrane-Like Intermediates Derived from Resorcinol and 2-Methylresorcinol," The Journal of Organic Chemistry, 2011, 76 (15), 6295-6308. doi:10.1021/jo201098c

V. M. Taylor, D. L. Cedeño, D. L. Muñoz, M. A. Jones, T. D. Lash, A. M. Young, M. H. Constantino, N. Esposito, I. D. Vélez, S. M. Robledo, “In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis,” Antimicrobial Agents and Chemotherapy, 2011, 55 (10), 4755-4764. doi:10.1128/aac.00671-11

T. D. Lash, "Unexpected Alkyl Group Migration in Palladium(II) Benzocarbaporphyrins," Organic Letters, 2011, 13 (17), 4632-4635. doi:10.1021/ol2018483

A. M. Young, A. L. Von Ruden, T. D. Lash, "Pyrazole Analogues of Porphyrins and Oxophlorins," Organic & Biomolecular Chemistry, 2011, 9 (18), 6293-6305. doi:10.1039/C1OB05603D

T. D. Lash, B. E. Smith, M. J. Melquist, B. A. Godfrey, "Synthesis of Indenoporphyrins, Highly Modified Porphyrins with Reduced Diatropic Characteristics," The Journal of Organic Chemistry, 2011, 76 (13), 5335-5345. doi:10.1021/jo2006895

T. D. Lash, A. M. Young, J. M. Rasmussen, G. M. Ferrence, "Naphthiporphyrins," The Journal of Organic Chemistry, 2011, 76 (14), 5636-5651. doi:10.1021/jo200622s

T. D. Lash, T. R. Lamm, J. A. Schaber, W.-H. Chung, E. K. Johnson, M. A. Jones, "Normal and Abnormal Heme Biosynthesis. Part 7. Synthesis and Metabolism of Coproporphyrinogen-III Analogues with Acetate or Butyrate Side Chains on Rings C and D. Development of a Modified Model for the Active Site of Coproporphyrinogen Oxidase," Bioorganic & Medicinal Chemistry, 2011, 19 (4), 1492-1504. doi:10.1016/j.bmc.2010.12.053

T. D. Lash, S. A. Jones, G. M. Ferrence, “Synthesis and Characterization of Tetraphenyl-21,23-dideazaporphyrin: The Best Evidence Yet That Porphyrins Really Are the [18] Annulenes of Nature,” Journal of the American Chemical Society, 2010, 132 (37), 12786-12787. doi:10.1021/ja105146a

P. Jain, G. M. Ferrence, T. D. Lash, “Preparation of Furan and Thiophene-Derived Fulvene Dialdehydes: Synthesis and Structural Characterization of a 22-Oxa-21-carbaporphyrin and a Related Palladium(II) Organometallic Complex,” The Journal of Organic Chemistry, 2010, 75 (19), 6563-6573. doi:10.1021/jo101310m

B. E. Smith, T. D. Lash, "Porphyrins with Exocyclic Rings. Part 25: Synthesis of Porphyrins with a Fused Cyclic Ether Subunit from Tetrahydro-4H-pyan-4-one," Tetrahedron, 2010, 66 (25), 4413-4422. doi:10.1016/j.tet.2010.04.069

T. D. Lash, U. N. Mani, A. I. M. Keck, M. A. Jones, "Normal and Abnormal Heme Biosynthesis. 6. Synthesis and Metabolism of a Series of Monovinylporphyrinogens Related to Harderoporphyrinogen. Further Insights into the Oxidative Decarboxylation of Porphyrinogen Substrates by Coproporphyrinogen Oxidase," The Journal of Organic Chemistry, 2010, 75 (10), 3183-3192. doi:10.1021/jo100083t

D. M. Gardner, V. M. Taylor, D. L. Cedeño, S. Padhee, S. M. Robledo, M. A. Jones, T. D. Lash, I. D. Vélez, “Association of Acenaphthoporphyrins with Liposomes for the Photodynamic Treatment of Leishmaniasis,” Photochemistry and Photobiology, 2010, 86 (3), 645-652. doi:10.1111/j.1751-1097.2010.00705.x

H. Boedigheimer, G. M. Ferrence, T. D. Lash, “Porphyrin on a Half-Shell! Synthesis and Characterization of Corannulenenoporphyrins,” The Journal of Organic Chemistry, 2010, 75 (8), 2518-2527. doi:10.1021/jo902592u

V. Gandhi, M. L. Thompson, T. D. Lash, "Porphyrins with Exocyclic Rings. Part 24. Synthesis and Spectroscopic Properties of Pyrenoporphyrins, Potential Building Blocks for Porphyrin Molecular Wires," Tetrahedron, 2010, 66 (10), 1787-1799. doi:10.1016/j.tet.2010.01.046