Valentine Group Research

--Avoiding rust and paint since 2001--

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. Some of our work includes:

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.

Ciona intestinalis from which nicaTf will soon be isolated

(photo credit: Jack Faller)

Arthur D. Tinoco, Cynthia W. Peterson, Baldo Lucchese, Robert P. Doyle, and Ann M. Valentine

On the Evolutionary Significance and Metal-binding Characteristics of a Monolobal Transferrin from Ciona intestinalis

Proc. Natl. Acad. Sci. USA 2008, 105, 3268-3273.

Ritika Uppal, K.V. Lakshmi, and Ann M. Valentine

Isolation and Characterization of the Primitive Monolobal Transferrin from Ciona intestinalis

J. Biol. Inorg. Chem. 2008, 13, 873-885.

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 (essentially making TiO₂ – white paint! – see our motto above). 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(IV)(citrate)₃^8-

Ritika Uppal, Christopher D. Incarvito, K. V. Lakshmi and Ann M. Valentine

Aqueous Spectroscopy and Redox Properties of Carboxylate-Bound Titanium

Inorg. Chem. 2006 45 1795-1804.

Joseph M. Collins, Ritika Uppal, Christopher D. Incarvito, and Ann M. Valentine

Titanium(IV) Citrate Speciation and Structure under Environmentally and Biologically Relevant Conditions

Inorg. Chem. 2005 44 3431-3440.

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.

Some interactions among Ti(IV) (from Cp₂TiCl₂) and human serum proteins

Arthur D. Tinoco, Emily V. Eames, Christopher D. Incarvito, and Ann M. Valentine

Hydrolytic Metal with a Hydrophobic Periphery: Titanium(IV) Complexes of Naphthalene-2,3-diolate and Interactions with Serum Albumin Inorg. Chem. 2008, in press.

Arthur D. Tinoco, Emily V. Eames, and Ann M. Valentine

Reconsideration of Serum Ti(IV) Transport: Albumin and Transferrin Trafficking of Ti(IV) and Its Complexes

J. Am. Chem. Soc. 2008, 130, 2262-2270.

Arthur D. Tinoco, Christopher D. Incarvito, and Ann M. Valentine

Calorimetric, Spectroscopic, and Model Studies Provide New Insight Into the Transport of Ti(IV) by Human Serum Transferrin

J. Am. Chem. Soc. 2007, 129, 3444-3454.

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.

Titanium phosphate induced by a polyamine catalyst

Kathryn E. Cole and Ann M. Valentine

Spermidine and Spermine Catalyze the Formation of Nanostructured Titanium Oxide

Biomacromolecules 2007, 8, 1641-1647

Kathryn E. Cole, Andrea N. Ortiz, Martin A. Schoonen, and Ann M. Valentine

Peptide- and Long-Chain Polyamine- Induced Synthesis of Micro- and Nanostructured Titanium Phosphates and Protein Encapsulation

Chem. Mater. 2006 18 4592-4599.

Kathryn E. Cole and Ann M. Valentine

Titanium Biomaterials: Titania Needles in the Test of the Foraminiferan Bathysiphon argenteus

Dalton Transactions 2006 3 430-432.

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