Our research centers on development of new fluorescent porphyrin-based macrocycles for application in medicine [e.g. diagnosis, photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer], and the study of their physicochemical and biological properties. Porphyrin-type compounds bear a number of key photochemical, photophysical and biological properties that make them highly desirable for medical applications: they absorb strongly in the visible region of the optical spectrum, have low dark toxicities, are chemical stable, have affinity for serum proteins and favorable pharmacokinetic properties, and form very stable complexes with a variety of metal ions. Several porphyrin-type compounds are currently in various stages of preclinical or clinical development as phototherapeutic agents; Photofrin® and VisudyneTM are two FDA-approved porphyrin-based photosensitizers for PDT.
The new macrocycles under development in our group are obtained either by derivatization of naturally occurring porphyrins (hemin and chlorophyll-a), or the preparation of new synthetic macrocycles containing special features for enhanced biological activity. Special emphasis is placed on the synthesis of polypyrroles containing both lipophilic side groups for interaction with cell membranes, and hydrophilic groups for solubilization in the blood stream, and with intense long-wavelength absorptions for enhanced photoactivity.
We investigate the mechanisms of cell uptake, retention and subcellular localization of the new compounds, and the influence of hydrophobicity, aggregation, charge and metalation on their biological activity. The spectroscopic characteristics of the new compounds and their acid-base properties, aggregation behavior, protein-binding affinities and interactions with DNA are studied in our laboratories, using primarily UV/Vis spectroscopy and fluorescence microscopy. The most promising candidates are further evaluated in animal models.
Fluorescence of H2DCP localized in the lysosomes of human keratinocyte HaCaT cells.
X-ray structure of Zn(II)-TCP, a promising new BNCT agent.
The study of heme polymerization and aggregation is also a goal of our research. These are important reactions in, for example, the treatment of hepatic porphyrias, which are genetic disorders of heme biosynthesis, and in malaria treatment.
New synthetic routes to covalently-linked porphyrin arrays are also goals of our research. These systems display unique photoelectronic properties and have potential applications as mimics of light-harvesting in photosynthesis, and as electron/energy transfer moieties in molecular wires. A variety of model structures have been prepared by us and others, containing two or three porphyrin units, either directly coupled, bridged by coplanar aromatic systems, or beta-fused. Coplanar-linked porphyrin arrays are believed to lead to more efficient energy- and electron-transfer superstructures. Metalloporphyrins are also synthesized in our laboratories for application as catalysts, in relation to their biological functions in hemoproteins and cytochrome P450.
Fully conjugated porphyrin pentamer
H. Li, N. Nguyen, F. R. Fronczek and M. G. H. Vicente. Syntheses and Properties of Octa-, Tetra- and Di-hydroxy-substituted Phthalocyanines. Tetrahedron 2009, 65, 3357-3363
E. Hao, T. J. Jensen and M. G. H. Vicente. Synthesis of porphyrin-carbohydrate conjugates using “click” chemistry and their preliminary evaluation in human HEp2 cells. Journal of Porphyrins and Phthalocyanines 2009, 13, 51-59
H. Li, F. R. Fronczek and M. G. H. Vicente. Cobaltacarborane-phthalocyanine conjugates: syntheses and photophysical properties. Journal of Organometallic Chemistry 2009, 694, 1607-1611
E. Hao, M. Zhang, W. E, K. M. Kadish, F. R. Fronczek, B. H. Courtney and M. G. H. Vicente. Synthesis and Spectroelectrochemistry of N-Cobaltacarborane Porphyrin Conjugates. Bioconjugate Chemistry 2008, 19, 2171-2181
I. Sehgal, M. Sibrian-Vazquez and M. G. H. Vicente. Photo-induced Cytotoxicity and Biodistribution of Prostate Cancer Cell-targetedPorphyrins. Journal of Medicinal Chemistry 2008, 51, 6014-6020
E. Hao, E. Friso, G. Miotto,G. Jori, M. Soncin, C. Fabris, M. Sibrian-Vazquez and M. G. H. Vicente. Synthesis and Biological Investigations of Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC). Organic and Biomolecular Chemistry 2008, 6, 3732 - 3740
M. Soncin, E. Friso, G. Jori, E. Hao, M. G. H. Vicente, G. Miotto, P. Colautti, D. Moro, J. Esposito, G. Rosi, and C. Fabris. Tumor-localizing and radiosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP). Journal of Porphyrins and Phthalocyanines 2008, 12, 866-873
M. W. Easson, F. R. Fronczek, T. J. Jensen and M. G. H. Vicente. Synthesis and in vitro Properties of Trimethylamine- and Phosphonate-substituted Carboranylporphyrins for Application in BNCT. Bioorganic and Medicinal Chemistry, 2008, 16, 3191-3208
H. Li, T. J. Jensen, F. R. Fronczek and M. G. H. Vicente. Syntheses and Properties of a Series of Cationic Water-Soluble Phthalocyanines. Journal of Medicinal Chemistry, 2008, 51, 502-511
M. Sibrian-Vazquez, I. V. Nesterova, T. J. Jensen, and M. G. H. Vicente. Mitochondria-Targeting by Guanidine- and Biguanidine-Porphyrin Photosensitizers. Bioconjugate Chemistry, 2008, 19, 705-713
M. Sibrian-Vazquez, T. J. Jensen, and M. G. H. Vicente. Synthesis, characterization, and metabolic stability of porphyrin-peptide conjugates bearing bifunctional signaling sequences. Journal of Medicinal Chemistry, 2008, 51, 2915-2923
H. Li, F. R. Fronczek and M. G. H. Vicente. Synthesis and properties of cobaltacarborane-functionalized Zn(II)-phthalocyanines. Tetrahedron Letters, 2008, 49, 4828-4830
M. Sibrian-Vazquez, J. Ortiz, I. V. Nesterova, F. Fernández-Lázaro, A. Sastre-Santos, S. A. Soper, and M. G. H. Vicente. Synthesis and Properties of Cell Targeted Zn(II)-phthalocyanine-peptide Conjugates. Bioconjugate Chemistry, 2007, 18, 410-420
L. Jiao, E. Hao, F. R. Fronczek, K. M. Smith and M. G. H. Vicente. Syntheses and Properties of Functionalized Oxacalix[4]arene Porphyrins. Tetrahedron, 2007, 63, 4011-4017
J. A. Hargus, F. R. Fronczek, M. G. H. Vicente, and K. M. Smith. Mono-(L)-aspartylchlorin-e6. Photochemistry and Photobiology, 2007, 83, 1006-1015
E. Hao, B. Fabre, F. R. Fronczek and M. G. H. Vicente. Poly[di(2-thiophenyl)carborane]s: Conducting Polymers with High Electrochemical and Thermal Resistance. Chemical Communications, 2007, 4387-4389
E. Hao, M. Sibrian-Vazquez, W. Serem, J. C. Garno, F. R. Fronczek and M. G. H. Vicente. Synthesis, Aggregation and Cellular Investigations of Porphyrin-Cobaltacarborane Conjugates. Chemistry – A European Journal, 2007, 13, 9035-9042
C. Fabris, M. G. H. Vicente, E. Hao, E. Friso, L. Borsetto, G. Jori, G. Miotto, P. Colautti, D. Moro, J. Esposito, A. Ferretti, C. R. Rossi, D. Nitti, G. Sotti and M. Soncin. Tumour-localizing and –photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP). Journal of Photochemistry & Photobiology, B: Biology, 2007, 89, 131-138
E. Hao, B. Fabre, F. R. Fronczek, and M. G. H. Vicente. Syntheses and Electropolymerization of Carboranyl-Functionalized Pyrroles and Thiophenes. Chemistry of Materials, 2007, 19, 6195–6205
M. Sibrian-Vazquez, T. J. Jensen, and M. G. H. Vicente. Porphyrin Retinamides: Synthesis and Cellular Studies. Bioconjugate Chemistry, 2007, 18, 1185-1193
L. Jiao, E. Hao, M. G. H. Vicente and K. M. Smith. An Improved Synthesis of Functionalized 2,2’-Bipyrroles. Journal of Organic Chemistry, 2007, 72, 8119-8122
M. Sibrian-Vazquez, T. J. Jensen and M. G. H. Vicente. Synthesis and Cellular Studies of PEG-functionalized meso-Tetraphenylporphyrins. Journal of Photochemistry and Photobiology, B: Biology, 2007, 86, 9-21
H. J. H. Wang, L. Jaquinod, M. M. Olmstead, M. G. H. Vicente, K. M. Kadish, Z. Ou, and K. M. Smith. Synthesis, Characterization, and Electrochemical Studies of ?,?’-Fused Metallocenoporphyrins. Inorganic Chemisty, 2007, 46, 2898-2913
M. Sibrian-Vazquez, T. J. Jensen, R. P. Hammer, and M. G. H. Vicente. Synthesis and Cellular Studies of Water Soluble Porphyrin-Peptide Conjugates. Proceedings of SPIE, The International Society for Optical Engineering, 2007, 6427, 64270A1-8
S. Nardis, G. Pomarico, F. R. Fronczek, M. G. H. Vicente and Roberto Paolesse. One-step Synthesis of Isocorroles. Tetrahedron Letters, 2007, 48, 8643-8646
M. Sibrian-Vazquez, E. Hao, T. J. Jensen and M. G. H. Vicente. Enhanced Cellular Uptake with a Cobaltacarborane-Porphyrin-HIV-1 Tat 48-60 Conjugate. Bioconjugate Chemistry, 2006, 17, 928-934
R. Luguya, T. J. Jensen, K. M. Smith and M. G. H. Vicente. Synthesis and Cellular Studies of a Carboranylchlorin for the PDT and BNCT of Tumors. Bioorganic and Medicinal Chemistry, 2006, 14, 5890-5897
E. Hao, F. R. Fronczek and M. G. H. Vicente. Oxacalixarene-Locked Bis-porphyrins and Higher Oligomers. Journal of Organic Chemistry, 2006, 71, 1233-1236
E. Hao, F. R. Fronczek and M. G. H. Vicente. Carborane functionalized pyrroles and porphyrins via the Suzuki cross-coupling reaction. Chemical Communications, 2006, 4900-4902
L. Jiao, E. Hao, F. R. Fronczek, M. G. H. Vicente and K. M. Smith. Benzoporphyrins via olefin ring-closure metathesis methodology. Chemical Communications, 2006, 3900-3902
O. Ongayi, M. G. H. Vicente, Z. Ou, K. M. Kadish, R. Kumar, F. R. Fronczek and K. M. Smith. Synthesis and Electrochemistry of Undeca-substituted Metallo-benzoylbiliverdins. Inorganic Chemistry, 2006, 45, 1463-1470
M. Sibrian-Vazquez, T. J. Jensen, R. P. Hammer and M. G. H. Vicente. Peptide-mediated Cell Transport of Water Soluble Porphyrin Conjugates. Journal of Medicinal Chemistry, 2006, 49, 1364-1372
D. Kessel, M. G. H. Vicente and J. J. Reiners Jr.. Initiation of Apoptosis and Autophagy by Photodynamic Therapy. Lasers in Surgery and Medicine, 2006, 38, 482-488
V. Gottumukkala, O. Ongayi, D. G. Baker, L. G. Lomax and M. G. H. Vicente. Synthesis, Cellular Uptake and Animal Toxicity of a Tetra(carboranylphenyl)-tetrabenzoporphyrin. Biorganic and Medicinal Chemistry, 2006, 14, 1871-1879
B. Fabre, J. C. Clark and M. G. H. Vicente. Synthesis and Electrochemistry of Carboranylpyrroles. Toward the Preparation of Electrochemically and Thermally Resistant Conjugated Polymers. Macromolecules, 2006, 39, 112-119
M. W. Renner, M. Miura, M. W. Easson and M. G. H. Vicente. Recent Progress in the Syntheses and Biological Evaluation of Boronated Porphyrins for BNCT. Current Medicinal Chemistry - Anti-Cancer Agents, 2006, 6, 145-158
M. Sibrian-Vazquez, T. J. Jensen, F. R. Fronczek, R. P. Hammer and M. G. H. Vicente. Synthesis and Characterization of Positively Charged Porphyrin-peptide Conjugates. Bioconjugate Chemistry, 2005, 16, 852-863
R. F. Barth, J. A. Coderre, M. G. H. Vicente and T. E Blue. Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects. Clinical Cancer Research, 2005, 11, 3987-4002
C. Poriel, D. Kessel and M. G. H. Vicente. Stability of Tin Etiopurpurin SnET2. Photochemistry and Photobiology, 2005, 81, 149-153
W. Liu, T. J. Jensen, F. R. Fronczek, R. P. Hammer, K. M. Smith and M. G. H. Vicente. Synthesis and in vitro Studies of Non-aggregated Water-soluble Phthalocyanines. Journal of Medicinal Chemistry, 2005, 48, 1033-1041
W. Liu, M. R. Kumar, M. G. H. Vicente, F. R. Fronczek and K. M. Smith. New Water-soluble Phthalocyanines and other Tetrapyrroles for Application in Photodynamic Therapy. Proceedings of SPIE, The International Society for Optical Engineering, 2005, 5689, 39-47
S. Nardis, R. Paolesse, S. Licoccia, F. R. Fronczek, M. G. H. Vicente, T. K. Shokhireva, S. Cai and F. A. Walker. NMR and Structural Investigations of a Nonplanar Iron Corrolate: Modified Patterns of Spin Delocalization and Coupling in a Slightly Saddled Chloroiron(III) Corrolate Radical. Inorganic Chemistry, 2005, 44, 7030-7046
K. M. Smith, S. H. Lee and M. G. H. Vicente. Porphyrins with beta-beta'-Fused Five-membered Rings. Journal of Porphyrins and Phthalocyanines, 2005, 9, 769-778
J. C. Clark, B. Fabre, F. R. Fronczek and M. G. H. Vicente. Syntheses and Properties of Carboranylpyrroles. . Journal of Porphyrins and Phthalocyanines, 2005, 9, 803-810
R. J. Luguya, F. R. Fronczec, K. M. Smith and M. G. H. Vicente. Carboranylcorroles. Tetrahedron Letters, 2005, 46, 5365-5368
W. Liu, F. R. Fronczek, M. G. H. Vicente and K. M. Smith. Diels-Alder Reactions of Pyrrolo[3,4-b]porphyrins. Tetrahedron Letters, 2005, 46, 7321-7324
E. Hao, T. J. Jensen, B. H. Courtney and M. G. H. Vicente. Synthesis and Cellular Studies of Porphyrin-Cobaltacarborane Conjugates. Bioconjugate Chemistry, 2005, 16, 1495-1502
E. Hao and M. G. H. Vicente. Expeditious Synthesis of Porphyrin-cobaltacarborane Conjugates. Chemical Communications, 2005, 1306-1308
V. Gottumukkala, R. Luguya, F. R. Fronczek and M. G. H. Vicente. Synthesis and Cellular Studies of an Octa-anionic 5,10,15,20-Tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin (H2OCP) for Application in BNCT. Bioorganic and Medicinal Chemistry, 2005, 13, 1633-1640
O. Ongayi, V. Gottumukkala, F. R. Fronczek and M. G. H. Vicente. Synthesis and Characterization of a Carboranyl-tetrabenzoporphyrin. Bioorganic and Medicinal Chemistry Letters, 2005, 15, 1665-1668
J. C. Clark, F. R. Fronczek and M. G. H. Vicente. Novel Carboranylporphyrins for Application in Boron Neutron Capture Therapy (BNCT) of Tumors. Tetrahedron Letters, 2005, 46, 2365-2368
R. Paolesse, S. Nardis, M. Stefanelli, F. R. Fronczek and M. G. H. Vicente. Hemiporphycene from Expansion of a Corrole Ring. Angewandte Chemie International Edition, 2005, 44, 3047-3050
D. Kessel, M. Conley, M. G. H. Vicente and J. J. Reiners, Jr. Studies on the Sub-cellular Localization of the Porphycene CPO. Photochemistry and Photobiology, 2005, 81, 569–572
| Former Graduate Students |
Hairong Li Ph.D., 12/08 Kiran Allam posthumously Ph.D., 08/08 Michael Easson Ph.D., 05/08 Erhong Hao Ph.D., 12/07 Vijay Gottumukkala Ph.D., 05/06 Jodie Hargus M.S., 12/05 Caroline Owendi Ongayi Ph.D.,12/05 Jefferey Caleb Clark Ph.D.,08/05
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