B.S. (1993) University of Virginia Ph.D. (1998) Massachusetts Institute of Technology postdoc (1998-2001) Pennsylvania State University

Biological Chemistry; Inorganic Chemistry

Our research in bioinorganic chemistry focuses on biologically relevant metals that are very sensitive to hydrolysis - mainly iron and titanium - and addresses how biology handles these difficult metals. Problems relate to metal uptake and transport, potential therapeutic applications thereof, and biomineralization. Nicatransferrin: Iron management proteins in higher organisms include transferrin. Serum transferrin in vertebrates is an approx. 80 kD bilobal protein that came from an ancient gene duplication of a primitive monolobal form. A monolobal transferrin (called nicatransferrin or nicaTf) was discovered in a group of marine invertebrate chordates called ascidians (or sea squirts). (Sea squirts are also well known to inorganic chemists for the ability of some species to sequester remarkable concentrations of unusual metals like vanadium and titanium.) We isolated the protein from the native organism and also expressed it in yeast. We are working to characterize this protein, partly to understand better how nature evolved the capacity to manage very hydrolysis-prone metals. Biologically and Environmentally Relevant Titanium Coordination Chemistry: Doing Ti(IV) chemistry in water, in the presence of oxygen and at neutral pH is tough, because Ti(IV) hydrolyzes so easily. We have worked to characterize complexes using ligands relevant to the coordination of Ti(IV) in biology and/or the environment that provide important models and allow us to address the questions below. Titanium and Proteins: Titanium(IV) is a bioactive metal ion, and Ti(IV)-containing molecules have been promising as anticancer drugs. We all have more titanium in our bodies than most people realize, and that is before getting a titanium alloy orthopedic implant, ingesting TiO2 in a pharmaceutical formulation, etc. We are characterizing the interactions between titanium ions and biomolecules to explore the nature of this bioactivity, and to exploit it for human benefit. Biotitanification: Usually we in the Valentine Group try to prevent titanium minerals from forming, but one of our projects asks whether organisms might use titanium in mineral form, or perhaps even actively biomineralize titanium. We have looked at whole organisms and worked with biomolecules modeling those found in diatoms, to understand the controlled mineraliztion of titanium.

Zhu, X.; Fryd, M; Valentine, A. M.; Wayland, B. B. “Detection of P. cepacia Lipase Isoforms by Corona Charge Selective Block Copolymer Micelle Degradation” 2014, 50, 964-967.

Amos, F. F.; Cole,K. E.; Meserole, R. L.; Gaffney, J. P; Valentine, A. M. “Titanium Mineralization in Ferritin: A Room Temperature Non-Photochemical Preparation and Biophysical Characterization” J. Biol. Inorg. Chem. 2013, 18, 145-152.

Buettner, K. M.; Collins, J. M.; Valentine, A. M. “Titanium(IV) and Vitamin C: Aqueous Complexes of a Bioactive Form of Ti(IV)” Inorg. Chem. 2012, 51, 11030-11039.

Tinoco, A. D.; Thomas, H. R.; Incarvito, C. D.; Saghatelian, A.; Valentine, A. M. “Cytotoxicity of a Ti(IV) Compound is Independent of Serum Proteins” Proc. Natl. Acad. Sci. USA 2012, 109, 5016-5021.

Buettner, K. M.; Valentine, A. M. “Bioinorganic Chemistry of Titanium” Chemical Reviews 2012, 112, 1863-1881.

Gaffney, J. P.; Valentine A. M. “Beyond Bilobal: Transferrin Homologs Having Unusual Domain Architectures” Biochimica et Biophysica Acta,2012, 1820, 212-217.

Buettner, K. M.; Snoeberger III, R.C.; Batista, V.S.; Valentine, A. M. “Pharmaceutical Formulation Affects Titanocene Transferrin Interactions” Dalton Transactions 2011, 40, 9580-9588.

Gaffney, J. P.; Valentine A. M. “The Challenges of Trafficking Hydrolysis Prone Metals and Ascidians as an Archetype” Dalton Transactions 2011, 40, 5827-5835.

Parker Siburt, C. J.; Lin, E. M.; Brandt, S. J., Tinoco, A. T.; Valentine, A. M.; Crumbliss, A. L. “Redox Potentials of Ti(IV) and Fe(III) Complexes Provide Insights Into Titanium Biodistribution Mechanisms” J. Inorg. Biochem. 2010, 104, 1006-1009.

Gaffney, J. P.; Valentine, A. M. “Contrasting Synergistic Anion Effects in Vanadium (V) Binding to Nicatransferrin Versus Human Serum Transferrin” Biochemistry 2009, 48, 11609-11611.

Uppal, R.; Israel, H. P.; Incarvito, C. D.; Valentine, A. M. “Titanium(IV) Complexes with N,N’-dialkyl-2,3-dihydroxyterephthalamides and 1-hydroxy-2(1H)-pyridinone as Siderophore and Tunichrome Analogues” Inorg. Chem. 2009, 48, 10769-10779.

Tinoco, A. D.; Eames, E. A.; Incarvito, C. D.; Valentine, A. M. “Hydrolytic Metal with a Hydrophobic Periphery: Titanium(IV) Complexes of Naphthalene-2,3-diolate and Interactions with Serum Albumin” Inorg. Chem. 2008, 47, 8380-8390.

Tinoco, A. D.; Eames, E. A.; Valentine, A. M. “Reconsideration of Serum Ti(IV) Transport: Albumin and Transferrin Trafficking of Ti(IV) and Its Complexes” J. Am. Chem. Soc. 2008, 130, 2262-2270.

Tinoco, A. D.; Peterson, C. W.; Lucchese, B.; Doyle, R. P.; Valentine, A. M. “On the Evolutionary Significance and Metal-binding Characteristics of a Monolobal Transferrin from Ciona intestinalis” Proc. Natl. Acad. Sci. USA 2008, 105, 3268-3273.

Uppal, R.; Lakshmi, K. V.; Valentine, A. M. “Isolation and Characterization of the Primitive Monolobal Transferrin from Ciona intestinalis” J. Biol. Inorg. Chem. 2008, 13, 873-885.

Cole, K. E.; Valentine, A. M. “Spermidine and Spermine Catalyze the Formation of Nanostructured Titanium Oxide” Biomacromolecules 2007, 8, 1641-1647

Tinoco, A. T.; Incarvito, C. D.; Valentine, A. M. “Calorimetric, Spectroscopic, and Model Studies Provide Insight Into the Transport of Ti(IV) by Human Serum Transferrin” J. Am. Chem. Soc. 2007, 129, 3444-3454.

Cole, K. E.; Ortiz, A. N.; Schoonen, M. A., Valentine, A. M. “Peptide- and Long-Chain Polyamine- Induced Synthesis of Micro- and Nanostructured Titanium Phosphates” Chem. Mater. 2006, 18, 4592-4599.

Uppal, R.; Incarvito, C. D.; Lakshmi, K. V.; Valentine, A. M. “Aqueous Spectroscopy and Redox Properties of Carboxylate-Bound Titanium” Inorg. Chem. 2006, 45, 1795-1804.

Cole, K. E.; Valentine, A. M. “Titanium Biomaterials: Titania Needles in the Test of the Foraminiferan Bathysiphon argenteus” Dalton Trans. 2006, 3, 430-432.