School of Physical, Environmental and Mathematical Sciences

Grant Collins

Associate Professor Grant Collins

Associate Professor, Research Coordinator

BSc PhD ANU, MRACI, CChem

Telephone: +61 2 6268 8077
Fax: +61 2 6268 8017
Email: g.collins@adfa.edu.au
Location: PEMS Nth, Room 214

My UNSW Research Gateway Profile

Research Interests:
Biological Chemistry ? (1) the interaction of inert transition metal complexes with DNA and (2) the development of metal based anticancer drugs.

Biological Chemistry

Biography

Grant Collins obtained his BSc Hons and PhD from the Australian National University. Following postdoctoral work at the University of New South Wales and a brief period at the Research School of Chemistry at the Australian National University, he was appointed to a lectureship at the University College in 1986.

Teaching

Research

Some of our work focuses on the interactions between transition metal complexes and DNA. This work aims at understanding the principles of DNA recognition, with the ultimate goal of being able to design compounds that can control gene expression - the next great target now that most of the human genome has been sequenced. We study the interactions of inert dinuclear ruthenium complexes with DNA. Dinuclear ruthenium complexes, rather than the more often studied mononuclear complexes, offer many advantages. Dinuclear complexes have an increased size and hence bind to a larger segment of DNA, and furthermore, they have a greater variety of shapes, greater DNA binding affinity and considerably slower DNA-dissociation rates.
We are also involved in the development of a new, and very promising, class of anti-cancer drug ? multinuclear platinum complexes. We design and synthesise new complexes, determine their biological activity and examine their binding to DNA by NMR spectroscopy. In addition, we are exploring the possibility of reducing the toxicity of multinuclear platinum complexes by encapsulating them in cucurbituril, an open-ended barrel shaped host molecule.

We are also involved in the development of new organic drugs based on the benzimidazole carbamate structure. Albendazole (ABZ) is a benzimidazole carbamate that has been in clinical use as an anti-parasitic drug for three decades. Our collaborators at the St George Hospital in Sydney hypothesized that ABZ may be an effective treatment against cancer.? They investigated the effect of the drug in vitro, in experimental animals and in a pilot study in cancer patients.? The studies revealed that ABZ is a potent inhibitor of tumor growth, and the pilot study showed for the first time the anti-tumor efficacy of ABZ in humans. These results indicate the potential of ABZ for the treatment of cancer.? More lately, we have been examining the effect of altering the structure of ABZ and studying the clinical consequences of encapsulating the benzimidazole carbamate drugs in cucurbituril.

 

Research Collaborators

Recent Publications

Book Chapters
  1. Day, A . I . and Collins, J .G. Cucurbituril receptors and drug delivery. In:Supramolecular Chemistry from Molecules to Nanomaterials, P.A. Steed & J.W. Steed (Eds), Wiley, 2011, Vol 2, in press.
  2. Hicks, M., Orkey, N.U. , Pisani, M.J., Collins, J.G., Wheate, N.J. and Aldrich-Wright, J.R. Using spectroscopic techniques in combination to examine drug-DNA interactions. In: Methods for Studying Nucleic Acid Drug Interactions, Y . Tor ( Ed.), to be published by Taylor and Francis in 2011.
  3. Buck, D.P and Collins, J.G. NMR Studies of Metallointercalator-DNA Interactions. In: Metallointercalators-Synthesis, Techniques to Probe Their Interactions with Biomolecules, J . R . Aldrich-Wright (Ed.), Springer, 2011, pp. 143-157.
  4. Smith, J .A., Collins, J.G. and Keene, F.R. Groove binding ruthenium(II) complexes as probes of DNA recognition, In: Metal Complexes - DNA Interactions , N. Hadjiliadis and E . Sletten (Eds ), Blackwell Publishing, Oxford, UK, 2009, pp. 319-346.
Journal publications
  1. Mulyana, Y., Collins, J.G. and Keene, F.R. Synthesis, nucleic acid binding and cytotoxicity of oligonuclear ruthenium complexes containing labile ligands. J. Incl. Phenom. Macrocycl. Chem., 2011, in press.
  2. Li, F., Mulyana, Y., Feteri, M., Warner, J., Collins, J.G. and Keene, F.R. The antimicrobial activity of inert oligonuclear polypyridylruthenium(II) complexes against a wide spectrum of bacteria, including MRSA. Dalton Trans., 2011 , 40, 5032?5038.
  3. Pisani, M. J., Fromm, P.D., Clarke, R.J., Mulyana, Y., K?rner, H., Heimann, K., Collins, J.G. and Keene, F.R. Mechanism of cytotoxicity and cellular uptake of lipophilic inert dinuclear polypyridylruthenium(II) complexes,ChemMedChem., 2011, 6, 848-858.
  4. Mulyana, Y., Weber, D.K., Buck, D.P., Motti, C., Collins, J.G. and Keene, F.R. Oligonuclear Polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: Synthesis, DNA-binding and cytotoxicity, Dalton Trans., 2011, 40, 1510-1523.
  5. Mansour, O.C., Evison, B.J., Sleebs, B.E., Watson, K.G., Nudelman, A., Rephaeli, A., Buck, D.P., Collins, J.G., Bilardi, R. A., Phillips, D.R. and Cutts, S.M. New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation. J. Med. Chem., 2010, 53, 6851-6866.
  6. Adnan, N., Buck, D.P., Evison, B.J., Cutts, S.M., Phillips, D.R. and Collins, J.G. DNA binding by pixantrone. Org . Biomol . Chem ., 2010, 8, 5359-5366.
  7. Zhao, Y., Pourgholami, M .H. , Morris, D. L ., Collins, J .G. and Day, A . I . Enhanced cytotoxicity of benzimidazole carbamate derivatives and solubilisation by encapsulation in cucurbit[ n ]uril. Org. Biomol. Chem., 2010 , 8, 3328-3337.
  8. Pisani, M.J., Zhao, Y., Wallace, L., Woodward, C.E. , Keene, F.R., Day, A.I. and Collins, J.G. Cucurbit[10]uril binding of dinuclear platinum(II) and ruthenium(II) complexes: Association/dissociation rates from seconds to hours. Dalton Trans ., 2010, 39, 2078-2086.
  9. Buck, D.P., Paul, J.A ., Pisani, M.J., Collins, J.G. and Keene, F.R. Binding of a flexibly-linked dinuclear ruthenium(II) complex to adenine-bulged DNA duplexes. Aust. J. Chem., 2010,63, 1365?1375.
  10. Pisani, M.J., Weber, D.K., Heimann, K., Collins, J.G. and Keene, F.R. Selective mitochodrial accumulation of cytotoxic dinuclear polypyridyl ruthenium(II) complexes. Metallomics, 2010, 2, 393-396.
  11. Pisani, M.J. , Wheate, N.J. , Keene, F.R. , Aldrich-Wright, J.R. and Collins, J.G. Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based drugs. J. Inorg. Biochem., 2009 , 103, 373-380.
  12. Keene, F.R., Smith, J.A. and Collins, J.G. Metal complexes as structure-selective binding agents for nucleic acids. Coordination Chem. Rev. 2009 , 253, 2021-2035.
  13. Zhao, Y., Bali, M.S., Cullinane, C., Day, A.I. and Collins, J.G. Synthesis, cytotoxicity and cucurbituril binding of triamine linked dinuclear platinum complexes. Dalton Trans., 2009, 5190-5198.
  14. Buck, D.P., Abeysinghe, P.M., Cullinane, C., Day, A.I., Collins, J.G. and Harding, M.M. Inclusion complexes of the antitumour metallocenes Cp2 MCl2 (M= Mo, Ti) with Cucurbit[ n ]urils. Dalton Trans., 2008, 2328-2334.
  15. Buck, D.P., Spillane, C.B., Collins, J.G. and Keene, F.R. Binding of a dinuclear ruthenium(II) complex to the TAR region of the HIV-AIDS viral RNA. Mol. BioSyst.., 2008, 4, 851-854.
  16. Zhao, Y., Buck, D.P., Morris, D.L., Pourgholami, M.H., Day, A.I. and Collins, J.G. Solubilisation and cytotoxicity of albendazole encapsulated in cucurbit[n ]uril. Org. Biomol. Chem., 2008, 6, 4509-4515.
  17. Spillane, C.B., Smith, J.A., Buck, D.P., Collins, J.G. and Keene, F.R. Dinuclear ruthenium(II) complexes as potential probes for RNA bulge sites. Dalton Trans., 2007, 5290-5296.
  18. Kemp, S., Wheate, N.J. , Wang, S., Collins, J.G., Ralph, S.F., Day, A.I., Higgins, V.J. and Aldrich-Wright, J.R. Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils. J. Biol. Inorg. Chem., 2007, 12, 969-979.
  19. 2Morgan, J.L., Spillane, C.B., Smith, J.A., Buck, D.P., Collins, J.G. and Keene, F.R. Dinuclear ruthenium(II) complexes with flexible bridges as non-duplex DNA binding agents. Dalton Trans., 2007 , 4333-4342.

  20. Wheate, N.J., Brodie, C.R., Collins, J.G., Kemp, S., and Aldrich-Wright, J.R. DNA intercalators in cancer therapy: organic and inorganic drugs and their spectroscopic tools of analysis. Mini-Reviews in Medicinal Chemistry, 2007, 7, 627-648.
  21. Kemp, S., Wheate, N.J., Buck, D.P., Nikac, M., Collins, J.G. and Aldrich-Wright, J.R. The effect of ancillary ligand chirality and phenanthroline functional group substitution on the cytotoxicity of platinum(II)-based metallointercalators. J. Inorg. Biochem., 2007, 101, 1049-1058.

  22. Bali, M.S., Buck, D.P., Coe, A.J. Day, A.I. and Collins, J.G. Cucurbituril binding of trans -[{PtCl(NH3) 2} 2 (m -NH2(CH2) 8 NH2)]2+ and the effect on the reaction with cysteine. Dalton Trans., 2006, 5337-5344.

  23. Morgan, J.L., Buck, D.P., Turley, A.G., Collins, J.G. and Keene, F.R. Selectivity at a three-base bulge site in the DNA binding of DD-[{Ru(phen)2}2(m-dppm)]4+{dppm = 4,6-bis(2-pyridyl)pyrimidine; phen = 1,10-phenanthroline} . J. Biol. Inorg. Chem., 2006, 11, 824-834.
  24. Smith, J.A., Morgan, J.L., Turley, A.G., Collins, J.G. and Keene, F.R. Meso-[{Ru(phen)2 }22(m-HAT)]4+ : a high-affinity DNA hairpin probe {HAT = 1,4,5,8,9,12-hexaazatriphenylene ; phen = 1,10-phenanthroline}. Dalton Trans., 2006, 3179-3187.
  25. Spillane, C.B., Morgan, J.L., Fletcher, N.C., Collins, J.G. and Keene, F.R. Inert benzothiazol functionalised ruthenium(II) complexes; potential DNA hairpin binding agents. Dalton Trans., 2006, 3122-3133.
  26. Wheate , N.J., Buck, D.P., Day, A.I. and Collins, J.G. Cucurbit[ n]uril binding of platinum anticancer complexes. Dalton Trans. 2006, 451-458.
  27. Jaramillo, D. J., Collins, J.G., Buck, D. P. , Fenton, R. , Stootman, F. and Aldrich-Wright, J.R. Synthesis, characterisation and biological activity of chiral platinum(II) compounds. Eur. J . Inorg. Chem., 2006, 839-849.
  28. Morgan, J.L., Buck, D.P., Turley, A.G., Collins, J.G. and Keene, F.R. Meso-[{Ru(phen)2}2(m-bpm)]4+: a high-affinity DNA bulge probe {bpm = 2,2'-bipyrimidine; phen = 1,10-phenanthroline}. Inorg. Chim. Acta , 2006, 359, 888-898.
  29. Wheate, N.J. and Collins, J.G. Multi-nuclear platinum drugs: A new paradigm in chemotherapy, Current Medicinal Chemistry-Anti-Cancer Agents, 2005, 5, 267-279.
  30. Collins, J.G. and Wheate, N.J. Potential adenine and minor groove binding platinum complexes, J. Inorg. Biochem.,2004,98, 1578-1584.
  31. Smith, J.A., Collins, J.G., Patterson, B.T. and Keene, F.R., Total enantioselectivity in the DNA binding of the dinuclear ruthenium(II) complex [{Ru(Me2 bpy)2}2(m-bpm)]4+ {bpm = 2,2'-bipyrimidine; Me 2 bpy = 4,4'-dimethyl-2,2'bipyridine} ,Dalton Trans ., 2004, 1277-1283.
  32. Wheate, N.J., Day, A.I., Blanch, R.J., Arnold, A.P., Cullinane, C. and Collins, J.G. , Multi-nuclear platinum complexes encapsulated in cucurbit[n]uril as an approach to reduce toxicity in cancer treatment,Chem. Commun., 2004, 1424-1425.
  33. Brodie, C.R., Collins, J.G. and Aldrich-Wright, J.R. The structure activity relationship of platinum(II) intercalating agents containing methyl-substituted 1,10-phenanthrolines,Dalton Trans., 2004, 1145-1152.
  34. Wheate, N.J. and Collins, J.G. Multi-nuclear platinum complexes as anti-cancer agents, Coord. Chem. Rev., 2003, 241, 133-145.
  35. Wheate, N.J., Evison, B.J., Herlt, A.J., Phillips, D.R. and Collins, J.G. DNA binding of the anti-cancer platinum complex trans--{Pt(NH3)2Cl}2(m-dpzm)]2+, J. Chem. Soc., Dalton Trans., 2003, 3486-3492.
  36. St Quintin, T.D., Leslie, D.R. and Collins, J.G. Hydrolysis of sesquimustards, Aust. J. Chem ., 2003,56,309-313.
  37. Freasier, B., Collins, G. and Newitt, P. A web-based interactive homework quiz and tutorial package: Motivating undergraduate chemistry students, J. Chem. Ed., 2003, 80, 1344-1347.
  38. Patterson, B.T., Collins, J.G., Foley, F.M. and Keene, F.R. Dinuclear ruthenium(II) complexes as probes for DNA bulge sites J. Chem.Soc., Dalton Trans., 2002, 4343-4350.
  39. Greguric, A., Greguric, I., Hambley, T.W., Aldrich-Wright,J.R. and Collins, J.G. Minor groove intercalation of D-[Ru(Me2 phen)2dppz)]2+ to the hexanucleotide d(GTCGAC)2 ,J. Chem. Soc., Dalton Trans, 2002, 849-855.
  40. Wheate, N.J., Cullinane, C., Webster, L.K. and Collins, J.G. Synthesis, cytotoxicity, cell uptake and interstrand cross-linking of dpzm linked platinum anti-cancer complexes. Anti-Cancer Drug Design, 2001, 16, 91-98.
  41. Foley, F.M., Keene, F.R. and Collins, J.G. The DNA Binding of the DD - DL and LL -Stereoisomers of [ {Ru(Me2 bpy)2}2 (m-bpm)]4+. J. Chem.Soc., Dalton Trans ., 2001, 2968-2974.
  42. Wheate, N.J., Broomhead, J.A., Collins, J.G. and Day, A.I. Thermal rearrangement of N-substituted pyrazoles to 4,4'-dipyrazolylmethane and 1,1,2-(4,4',4?-tripyrazolyl)ethane. Aust. J. Chem. , 2001, 54, 141-144.
  43. MacLeod, J.K., Flanigan, I.L., Williams, J.F. and Collins, J.G. Mass spectrometric studies of the path of carbon in photosynthesis: Positional isotopic analysis of 13 C-labelled C4 to C 7 sugar phosphates . J. Mass Spectrometry, 2001, 36, 500-508.
  44. Wheate, N.J., Cutts, S.M., Phillips, D.R., Aldrich-Wright, J.R. and Collins, J.G. The binding of [(en)Pt(m -dpzm)2 Pt(en)]4+ to G/C Rich Regions of DNA. J. Inorg. Biochem., 2001, 84, 119-127.
  45. Collins, J.G., Rixon, R.M. and Aldrich-Wright, J.R. Interaction of [Pt(en)(phen)] 2+ and [Pt(en)(phi]2+ with the hexanucleotide d)GTCGAC)2 : Evidence for minor groove binding. Inorg. Chem., 2000, 39, 4377-4379.
  46. Wheate, N.J. and Collins, J.G. A 1 H NMR study of the oligonucleotide binding of [(en)Pt mdpzm)2Pt(en)]Cl4. J. Inorg. Biochem., 2000, 78, 313-320.
  47. Wheate, N.J., Webster, L.K., Brodie, C.R. and Collins, J.G. Synthesis, DNA binding and cytotoxicity of isohelical DNA groove binding platinum complexes. Anti-Cancer Drug Design, 2000, 15, 313-321.