Marzilli, Luigi - Louisiana State University

研究领域

Our research program is devoted to applying physical and synthetic chemical methods to solving problems of biological and medical relevance. We explore the fundamental chemistry of simpler compounds as well as large biomolecules with the goal of understanding how metal species function in complex living systems. Toward this end, we rely heavily on both synthetic chemistry and on physical techniques including 2D and dynamic NMR and X-ray crystallography. We often undertake rate studies to determine the relationship between structure and reactivity. Members of my group have diverse research opportunities ranging from the exclusively synthetic to the exclusively quantitative. Transition metal species are found in compounds essential for life-Co in vitamin B-12, Fe in hemoglobin, and Zn, Cu, Mo, etc., in metalloenzymes. Metals have been incorporated into drugs (Pt in anticancer agents, Au in antiarthritic agents) and in diagnostic contrast agents (Tc, Gd) and also may function as pollutants (Cd, Hg, Pb and others). Metallo Anticancer Drugs We examine the binding of drugs to large molecular species, such as nucleic acids, using many physical and analytical techniques including 31P and 1H NMR. My group also studies deoxyribonucleotides, which are synthetic pieces of the DNA double helix. Recently this work has provided new insights into the potential mode of action of Pt anticancer drugs, which are now the most widely used anticancer drugs in the world. Metals in the Diagnosis of Disease In a joint program with the Division of Nuclear Medicine, we are examining the synthesis of ligands and Tc-99m complexes with the aim of developing new diagnostic agents for studying kidney and heart function and also for imaging the brain. This program combines traditional synthetic chemistry with modern medical knowledge and instrumentation to solve important health problems. Metals in Biology and as Probes of Biomolecular Structure We prepare organocobalt compounds that are models for coenzyme B-12 and serve as probes of biomolecule structures. For example, organocobalt porphyrins bind to DNA and reveal features of the DNA structure through distinct spectral and reactivity patterns. Zinc plays an important role in biology and zinc is an important component of enzymes which repair DNA and catalyze the hydrolysis of phosphodiester linkages.

近期论文

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Jamil S. Saad, Patricia A. Marzilli, Francesco P. Intini, Giovanni Natile, and Luigi G. Marzilli, "Single-stranded Oligonucleotide Adducts Formed by Pt Complexes Favoring Left-handed Base Canting: Steric Effect of Flanking Residues and Relevance to DNA Adducts Formed by Pt Anticancer Drugs," Inorg. Chem., 50, 8608-8620 (2011). Vidhi Maheshwari, Patricia A. Marzilli, and Luigi G. Marzilli, "Investigation Relevant to the Conformation of the 17-Membered Pt(d(GpG)) Macrocyclic Ring Formed by Pt Anticancer Drugs with DNA: Pt Complexes with a Goldilocks Carrier Ligand," Inorg. Chem., 50, 6626-6636 (2011). Jamil S. Saad, Michele Benedetti, Giovanni Natile, and Luigi G. Marzilli, "NMR Studies of Models Having the Pt(d(GpG)) 17-Membered Macrocyclic Ring Formed in DNA by Platinum Anticancer Drugs: Pt Complexes with Bulky Chiral Diamine Ligands," Inorg. Chem., 50, 4559-4571 (2011). Francesco P. Intini, Renzo Cini, Gabriella Tamasi, Michael B. Hursthouse, Luigi G. Marzilli, and Giovanni Natile, X-ray Structural Characterization of the Bis-Guanine Derivative of a Cisplatin Analogue Having Just One Proton on Each Coordinated Nitrogen and a Head-to-Head Conformation: [Pt{(±)-N,N'-dimethylbutane-2,3-diamine}(9-ethyl-guanine)2]dinitrate," Inorg. Chem., 49, 7853-7860 (2010). Theshini Perera, Frank R. Fronczek, Patricia A. Marzilli, and Luigi G. Marzilli, "Superbasic Amidine Monodentate Ligands in fac-[Re(CO)3(5,5'-Me2bipy)(Amidine)]BF4Complexes: Dependence of Amidine Configuration on the Remote Nitrogen Substituents," Inorg. Chem. 49, 7035-7045 (2010). Jamil S. Saad, Michele Benedetti, Giovanni Natile,and Luigi G. Marzilli, "Basic Coordination Chemistry Relevant to DNA Adducts Formed by the Cisplatin Anticancer Drug. NMR Studies on Compounds with Sterically Crowded Chiral Ligands," Inorg. Chem., 49, 5573-5583 (2010). Theshini Perera, Patricia A. Marzilli, Frank R. Fronczek, and Luigi G. Marzilli, "NH NMR Shifts of New Structurally Characterized fac-[Re(CO)3(polyamine)]n+Complexes Probed via Outer-Sphere Hydrogten-Bonding Interactions to Anions, Including the Paramagnetic [ReIVBr6]2- Anion," Inorg. Chem., 49, 5560-5572 (2010). Andrew T. Taylor, Malgorzata Lipowska, and Luigi G. Marzilli, "99mTc(CO)3(NTA): A 99mTc Renal Tracer with Pharmacokinetic Properties in Normal Volunteers Comparable to Those of 131I-OIH, " J. Nucl. Med., 51, 391-396 (2010). Malgorzata Lipowska, Haiyang He, Xiaolong Xu, Andrew T. Taylor, Patricia A. Marzilli, and Luigi G. Marzilli, "Multidentate Ligand Linkage Isomerism of fac-[Re(CO)3(polyaminocarboxylate)] Analogues of 99mTc Radiopharmaceuticals. Dependence on Solution pH," Inorg. Chem., 49, 3141-3151 (2010). Theshini Perera, Patricia A. Marzilli, Frank R. Fronczek, and Luigi G. Marzilli, "Several Novel N-Donor Tridentate Ligands Formed in Chemical Studies of New fac-Re(CO)3Complexes Relevant to fac-99mTc(CO)3Radio-pharmaceuticals. Attack of a Terminal Amine on Coordinated Acetonitrile," Inorg. Chem., 49, 2123-2131 (2010). Jamil S. Saad, Giovanni Natile,and Luigi G. Marzilli, "Origins of the Distortions in the Base-Pair Step Adjacent to Platinum Anticancer Drug-DNA Adducts. Fundamental NMR Solution Studies Utilizing Right-Handed Cross-link Models Having 5'- and 3'-Flanking Residues," J. Am. Chem. Soc., 131, 12314–12324 (2009). Jamil S. Saad, Giovanni Natile, and Luigi G. Marzilli, "Origins of the Distortions in the Base Pair Step Adjacent to Platinum Anticancer Drug-DNAAdducts. Fundamental NMR Solution Studies Utilizing Right-Handed Crosslink Models Having 5'- and 3'-Flanking Residues," J. Am. Chem. Soc., in press (2009). Janet Manono, Patricia A. Marzilli and Luigi G. Marzilli, "New Porphyrins Bearing Positively Charged Peripheral Groups Linked by a Sulfonamide Group to meso-Tetraphenylporphyrin: Interactions with Calf Thymus DNA," Inorg. Chem., 48, 5636-5647 (2009). Janet Manono, Patricia A. Marzilli, Frank R. Fronczek and Luigi G. Marzilli, "New Porphyrins Bearing Pyridyl Peripheral Groups Linked by Secondary or Tertiary Sulfonamide Groups: Synthesis and Structural Characterization," Inorg. Chem., 48, 5626-5635 (2009). Scott J. Moore, Patrizia Siega, Rene J. Lachicotte, Lucio Randaccio, Patricia A. Marzilli, and Luigi G. Marzilli, "Effects of Equatorial Ligand Bulk on the Orientation of Axial Ligands in Methyl Organocobalt B12 Models Assessed by X-Ray and NMR Methods," Inorg. Chim. Acta, 362, 993-1002 (2009). Malgorzata Lipowska, Luigi G. Marzilli, and Andrew T. Taylor, "99mTc(CO)3-Nitrilotriacetic Acid: A New Renal Radiopharmaceutical Showing in Rats Pharmacokinetic Properties Comparable to Those of 131I-OIH", J. Nucl. Med., 50, 454-460 (2009).