研究领域

Materials/Biological/Synthesis

The targets of ruthenium-based antitumour compounds have yet to be defined, however, and so the rationale design of new, more potent compounds presents a problem. Recently, a small body of research has been aimed at the "directing" of precious metal interactions to specific enzymatic targets by connection of such complexes to an organic ligand. Precious metals are ideally suited to this end; their (relatively slow) ligand exchange rates are similar to the lifetimes of cellular processes and they are capable of forming highly energetically-favourable coordination bonds to the physiological target. Owing to their enthalpic favourability, as few as one or two such bonds would be sufficient to impart a marked increase on target inhibition. Indeed, given the hypothesis of Kuntz et al7, it is predicted that compounds of this nature should display augmented ligand efficiency compared with the organic directing molecule alone. The aim of my research is to build ruthenium organometallic groups into validated, medicinal compounds such that the ligand efficiency of these existing compounds can be improved upon. In the longer term, it is hoped that the central approach described will set a precedent for inclusion of metal-containing fragments in libraries for fragment assembly. The capacity to dramatically increase ligand efficiency and to offer tunable lability and variable hypervalancy within a library could signal a new era in the field of fragment-based drug discovery and medicinal pharmaceuticals.

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Cobalt Catalyzed Carbon Nanotube Growth on Graphitic Paper Supports. V Engels, J Geng, GM Jones, JA Elliott, AEH Wheatley, SR Boss – Current Nanoscience (2011) 7, 315. (DOI: 10.2174/157341311795542471) Tuning heavy metal compounds for anti-tumor activity: is diversity the key to ruthenium’s success? SM Page, SR Boss, PD Barker – Future Med Chem (2009) 1, 541. (DOI: 10.4155/FMC.09.25) Groups 1 and 11: The alkali and coinage metals. SR Boss, AEH Wheatley – Organometallic Chemistry (2007) 33, 1. (DOI: 10.1039/9781847558503-00001) Encapsulation of hydride by molecular main group metal clusters: manipulating the source and coordination sphere of the interstitial ion. SR Boss, MP Coles, V Eyre-Brook, F García, R Haigh, PB Hitchcock, M McPartlin, JV Morey, H Naka, PR Raithby, HA Sparkes, CW Tate, AE Wheatley – Dalton transactions (Cambridge, England : 2003) (2006) 5574. (DOI: 10.1039/b612782g) Syntheses, structures and magnetic properties of Mn(ii) dimers [CpMn(�-X)]2(Cp = C5H5; X = RNH, R1R2N, C?CR). CS Alvarez, SR Boss, JC Burley, SM Humphry, RA Layfield, RA Kowenicki, M McPartlin, JM Rawson, AE Wheatley, PT Wood, DS Wright – Dalton transactions (Cambridge, England : 2003) (2004) 3481. (DOI: 10.1039/B409135C) The structural characteristics of organozinc complexes incorporating N,N'-bidentate ligands. SJ Birch, SR Boss, SC Cole, MP Coles, R Haigh, PB Hitchcock, AE Wheatley – Dalton transactions (Cambridge, England : 2003) (2004) 3568. (DOI: 10.1039/b410945g) Hydride encapsulation by a molecular main-group-metal cluster: Single-crystal neutron diffraction structure of [{Ph(2-C5H4N}(6)HLi8](+). SR Boss, JM Cole, R Haigh, R Snaith, AEH Wheatley, GJ McIntyre, PR Raithby – Organometallics (2004) 23, 4527. (DOI: 10.1021/om049661l) Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides. DR Armstrong, SR Boss, J Clayden, R Haigh, BA Kirmani, DJ Linton, P Schooler, AE Wheatley – Angew Chem Int Ed Engl (2004) 43, 2135. (DOI: 10.1002/anie.200353324) Toward an understanding of the oxygen scavenging properties of lithium zincates. SR Boss, R Haigh, DJ Linton, AEH Wheatley – Phosphorus, Sulfur and Silicon and the Related Elements (2004) 179, 929. (DOI: 10.1080/10426500490428915) Ligand and metal effects on the formation of main-group polyhedral clusters. SR Boss, MP Coles, R Haigh, PB Hitchcock, R Snaith, AE Wheatley – Angew Chem Int Ed Engl (2003) 42, 5593. (DOI: 10.1002/anie.200351921) New motifs in lithium zincate chemistry: a solid-state structural study of PhC(O)N(R)ZnR ' Li-2 center dot 2thf (R, R ' = alkyl, aryl) and [PhC(O)N(Ph)Li center dot thf]center dot[PhC(O)N(Ph)Zn(Bu-t)(2)Li center dot thf]. SR Boss, R Haigh, DJ Linton, P Schooler, GP Shields, AEH Wheatley – DALTON T (2003) 1001. (DOI: 10.1039/b210479b) Oxygen scavenging by lithium zincates: The synthesis, structural characterisation and derivatisation of [Ph(2-C5H4N)N]2ZnRLi·nthf (R = But, Bun; n = 1, 2). SR Boss, R Haigh, DJ Linton, AEH Wheatley – Journal of the Chemical Society, Dalton Transactions (2002) 3129. (DOI: 10.1039/b203451d)