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A new class of magnetic resonance (MR) contrast agents that uses a self-immolative mechanism for activation in the presence of an enzyme is reported. A Gd(III) agent that is activated by the oncologically significant beta-glucuronidase is synthesized in nine steps.

Research has been conducted on the intracellular Ca (super)2+ and its regulation in living animals. The use of the MRI contrast agent where the complex relaxivity is controlled by the absence or presence of the divalent ion Ca (super)2+ is described.

The detection of a point mutation using dual-signaling probes on CMS-DNA arrays coupled to an electrochemical reader is described. The results show that rapid and accurate detection of a single-base mismatch is achieved by using these dual-signaling probes on CMS-DNA chips.

Metal complexes that bind to an enzyme's active site could be used to inhibit the enzyme if excess enzymatic activity is causing disease. However, the metal complex must be specific to that enzyme, must be stable, non-toxic, and bioavailable, and must produce no compensatory effects.

Axial ligation X affects reduction potentials more than equatorial substituents B and A in a study of the electrochemical properties of cobalt(III) derivatives of acacen (H2acacen = bis(acetylacetone) ethylenediimine). The lowest pi-pi* intraligand charge-transfer transition is responsible for the absorption between 340-378 nm in CoIII(acacen) spectra. A study is presented of Co(III) interactions with nucleic acids and proteins, with some cobalt(III) Schiff base complexes known to be antiviral agents.

The first steroid conjugated hormone magnetic resonance (MR) contrast agent is synthesized to track cell signaling processes upon binding to a transcriptional system. By combining a transcriptional system and a noninvasive imaging technology, the compound successfully crossed cell membranes and modulated gene transcription.

A simple and inexpensive method is used to prepare three new low molecular weight, monodispersed magnetic resonance (MR) contrast agents with multiple Gd(III) complexes. The agents have increased relaxivity and good biocompatibility and do not affect cellular viability in culture, while are also able to effectively label cells, as observed in acquired MR images.

An analogous strategy is described for controlling the length of a self-assembled nanofiber by using a rigid template. The shape control within the molecular template has led to greater complexity in the supramolecular nanostructure.

Mechanistic investigation of isomeric series of [beta]-galactosidase-activated magnetic resonance contrast agents is reported. In the [alpha]-isomer the carbonate ion and [beta]-isomers the galactopyranose play a role in the mechanism of water exclusion from the lanthanide centre prior to cleavage.

Gd(III)-modified DNA-Ti[O.sub.2] semiconducting nanoparticle is prepared and it can be detected in cells by magnetic resonance (MR) imaging. The studies have shown that any dopamine-functionalized molecule can be linked to this modified Ti[O.sub.2] nanoparticle scaffold, which has allowed noninvasive monitoring of cells containing target molecules and removal of target gene sequences pending Ti[O.sub.2] oxidation.

The synthesis and characterization of various new ruthenium and rhenium complexes are discussed. The site-selective incorporation of the complexes on DNA enables the measurement of the ground-state electron transfer (ET) rates between the donor and acceptor.

The first MRI prodrug-procontrast complex is prepared by conjugating doxorubicin to a Gd(III) chelate using an acid-ladible linker. The relaxometric properties of the adduct and pH activation are presented.

A generalized methodology is presented for the synthesis of 5' metalated thymidines, which serve as electron donor-acceptor pair with spectroscopic signatures of the ruthenium(II) oxidation state. Data indicate that both electron donor and acceptor ruthenium complexes incorporateinto the 5' end of oligonucleotides with marginal to no change either to the metal complex or the DNA duplex structure.

The first synthesis of metallonucleoside bound to a solid support and subsequent oligonucleotide synthesis with this precursor is reported. It was seen that despite the relatively high Ru(III/II) reduction potential, oxidative quenching of photoexcited [Ru(bpy)(sub 2)(impy)](super 2+) does not lead to oxidative damages of guanine or other DNA bases.

A new class of contrast agents for magnetic resonance imaging (MRI) has emerged that is sensitive to biochemical activity. Enzyme-activated agents offer the possibility of mapping gene expression in living animals, whereas pH-sensitive agents are of particular interest for detection of abnormal tissue. Contrast agents selective for calcium, an important second messenger, can provide information about signal transduction events. Other efforts in contrast agent development are directed toward improving delivery by conjugating contrast agents to moieties that target certain tissues or that facilitate uptake. The development of new agents introduces a means for using MRI to probe biochemical activity in living organisms.

The synthesis and electrochemical characterization of the five biotin- and desthiobiotin-containing metal complexes in both free and protein-bound environments is reported. Cyclic voltammetry experiments confirm that binding of the metal complexes to avidin takes place in a manner consistent with the native ligand-receptor pair, and those complexes, while bound are electrochemically addressable.

Ferrocene deoxyribonucleic acid oligonucleotides were coupled to uridine and examined. The results which revealed a surprising cyclization reaction of the uridine base are presented.

Research is presented concerning the use of spectroscopy to investigate the electrochemistry of a chelating nucleoside which enables the creation of a series of metallonucleosides. The incorporation of metal complexes into DNA is discussed.

A study on Ca2+ in signal transduction reports on the first magnetic resonance imaging contrast agent called DOPTA-Gd whose relaxivity is selectively modulated by Ca2+ concentration. DOPTA-Gd has a Ca2+ dissociation constant of 0.96 muM and its relaxivity increases roughly 80% when Ca2+ is added to a Ca2+-free solution. The study is part of attempts to investigate cell signalling and regulation in intact animals.

The selective inhibition of human alpha-thrombin by cobalt(III) Schiff base complexes was studied by examining the selectivity of a chelate in a mixture of enzymes composed of chymotrypsin, thermolysin and thrombin. The results revealed the inhibition of thrombin, while chymotrypsin and thermolysin were not inhibited. The inhibition of the enzyme was attributed to the binding of the chelate in the active-site region since enzymatic activity was not diminished when thrombin was incubated with 100 micromolar concentrations of leupeptin.