A chromatographic tool for preparing combinatorial quinone-thiol conjugate libraries.
Quinones are well established as key players in the production of reactive oxygen species within cellular environments. Many factors govern their cytotoxicity but most studies have been restricted to a few, core, derivatives. A new strategy for the in situ production of quinone derivatives has been developed such that libraries of diverse functionality can be rapidly created without recourse to extensive synthetic procedures. The approach relies upon nucleophilic addition by reduced thiol derivatives to the quinone core within a pre-culture assay mixture and provides a generic strategy that exploits the large reservoir of commercial thiols currently available. A readily accessible chromatographic method has been developed that allows the derivatisation process to be easily monitored and the purity of the resulting one pot preparation to be assessed. The viability of the combinatorial approach has been fully validated through comparison with a range of quinone-S-conjugates prepared using conventional bench synthesis. The latter have been fully characterised.
Villalba
Maria Marti
MM
School of Biomedical and Natural Sciences, Nottingham Trent University, Nottingham, NG11 8NS, UK.
Litchfield
Verity J
VJ
Smith
Robert B
RB
Franklin
Anthony M
AM
Livingstone
Callum
C
Davis
James
J
D002853:Chromatography, Liquid / Q000379:methods*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D011809:Quinones; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds