A number of other projects have been or are being studied in our laboratories. In some cases, these have arisen as natural extensions of chemistry uncovered from the investigations described above.
Nitrogen-Oxide Cu or Fe Chemistry
We have been off-and-on interested in the chemistry of nitrogen oxides (e.g., NO, N2O, NO2-) (see publications #77, #85, #135), since their chemistry is of environmental significance, nitrite (NO2-) and nitrous oxide (N2O) are natural substrates for copper enzymes (for example in detrifying bacteria), and (as mentioned above), NO(g) is a substrate for a heme/non-heme diiron active site in NO Reductase. Nitric oxide has also been used to probe the active site chemistry of iron and copper enzymes, since NO(g) is considered an O2 surrogate. We have found that NO(g) readily reacts with our copper(I) complexes, with evolution of N2O, and these reactions are being studied mechanistically. Structural, spectrsocopic and rectivity models for NO Reductase are also being investigated. We are also trying to design compounds which may be reactive enough to deoxygenate nitrous oxide, which is kinetically highly inert, but which is known to be reduced at a dicopper enzyme active center in Nitrous Oxide Reductase.
The actives sites of a variety of hydrolases, for example enzymes which carry out ester (e.g. phosphate esters) or amide (peptide) hydrolysis reactions, often contain binuclear or trinuclear metal active sites. The metal ion involved may be zinc, manganese, nickel, iron, magnesium, or even copper as a substitute has activity. A key feature of the chemistry appears to be a metal-hydroxide or M-(OH)-M moiety. In our copper-dioxygen chemistry studies, binuclear or trinuclear copper-hydroxide complexes have been generated and characterized. As a consequence, we have studies several examples of dicopper complex mediated hydrolysis, and have found our compounds are capable of hydrolysis of unactived amides (publication #113), esters or even nitriles (publication #144), and carbon dioxide (publication # 108). A novel case occurs when hydrolysis of amides can be effected through direct copper-dioxygen chemistry (#113 ). Continued study of hydrolysis chemistry with synthetically designed multimetal (Zn, Cu, Mn) complexes is planned.
Reactions of Copper Complexes with DNA/Proteins
The study of metal complexes which are capbable of oxidative chemistry and/or hydrolytic activity is of interest with respect to interactions with DNA or proteins. Metal complexes may be utilized as ‘footprinting’ agents to help probe DNA or protein structure, and/or DNA/protein complexes which are important in gene regulation. Copper complexes, especially a Cu-phenanthroline species, has been found to be of considerable biochemical or biotechnological interest. Thus, with the many types of redox and hydrolytically active compounds studied in our group, we have a small but active ongoing effort to survey our complexes in this regard. Initial studies (see publication #138) show that a trinuclear complex we have synthesized is very active in oxidative cleavage of DNA plasmids. Further studies are in progress, aimed at a better mechanistic understanding, discovering possible hydrolytic processes, and extending the investigations to peptides or proteins.
Thorough characterization of complexes generated in our group inlucdes characterization of NMR-spectroscopy. Interestingly, a number of dicopper(II) complexes we have studies show very sharp, but paramagnetically shifted proton NMR signals. Ligand-based NMR signals for copper(II) complexes is unusual because of unfavorable relaxation times, but the binuclear nature of the complexes is seen to be responsible (see publication #140). Further investigation will seek to broaden the scope of complex type exhibiting this kind of NMR spectroscopic behavior, and the application to characterization paramagnetic multinuclear copper complexes involved in O2-binding or oxidative chemistry. We have also studied (publication #146) and are continuing to study in some detail the highly interesting NMR-spectroscopic behavior of antiferromagnetically coupled Fe(III)-X-Cu(II) (S = 2) systems, relevant to our heme-copper model program (see above).