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PEMS Staff Photo Assoc Prof Grant Collins

Assoc. Prof. Grant Collins

Assoc. Prof./Discipline Coordinator Chemistry
BSc PhD A.N.U., MRACI, CChem

School of Physical, Environmental and Mathematical Sciences
UNSW @ ADFA
Canberra   ACT   2600
AUSTRALIA

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

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
  • Chemistry 1
  • Organic Chemistry in 2nd year
  • Biological Chemistry in 3rd year
  • Chemical and Biological Defence (a General Education course)
Research

My research primarily 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.

In addition, 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.

Research Collaborators
  • Professor Richard Keene - James Cook University.
  • Professor Nick Farrell - Virginia Commonwealth University, USA.
  • A/Professor Janice Aldrich-Wright - University of Western Sydney.
Recent Publications

Book Chapters

1. “Groove binding ruthenium(II) complexes as probes of DNA recognition” in “Metal Complexes - DNA interactions” (Eds, N. Hadjiliadis and E. Sletten), Wiley Publishing, Oxford, UK. Smith, J.A., Collins, J.G. and Keene, F.R., 2009, pp. 319-346.

2. “NMR Studies of Metallointercalator-DNA Interactions” in “Metallointercalators-Synthesis, Techniques to Probe Their Interactions with Biomolecules ” (Ed. J.R. Aldrich-Wright), Springer, Buck, D.P and Collins, J.G., 2009, in press.

Journal publications

3. “Synthesis, cytotoxicity and cucurbituril binding of triamine linked dinuclear platinum complexes.” Zhao, Y., Bali, M.S., Cullinane, C., Day, A.I. and Collins, J.G., Dalton Trans., 5190-5198 (2009).

4. “Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based drugs.” Pisani, M.J., Wheate, N.J., Keene, F.R., Aldrich-Wright, J.R. and Collins, J.G., J. Inorg. Biochem., 103, 373-380 (2009)

5. “Metal Complexes as Structure-Selective Binding Agents for Nucleic Acids.” Keene, F.R., Smith, J.A. and Collins, J.G., Coord. Chem. Rev., 253, 2021-2035 (2009).

6. “Binding of a dinuclear ruthenium(II) complex to the TAR region of the HIV-AIDS viral RNA.” Buck, D.P., Spillane, C. B., Collins, J.G. and Keene, F.R., Mol. BioSyst., 4, 851-854 (2008).

7. “Solubilisation and cytotoxicity of albendazole encapsulated in cucurbit[n]uril.” Zhao, Y., Buck, D.P., Morris, D.L., Pourgholami, M.H., Day, A.I. and Collins, J.G., Org. Biomol. Chem., 6, 4509-4515 (2008).

8. “Inclusion Complexes of the Antitumour Metallocenes Cp2 MCl2 (M= Mo, Ti) with Cucurbit[n]urils.” Buck, D.P, Abeysinghe, P.M., Cullinane, C., Day, A.I., Collins, J.G. and Harding, M.M., Dalton Trans., 2328-2334 (2008).

9. “Dinuclear ruthenium(II) complexes as potential probes for RNA bulge sites.” Spillane, C.B., Smith, J.A., Buck, D.P., Collins, J.G. and Keene, F.R., Dalton Trans., 5290-5296, (2007).

10. “Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils.” Kemp, S., Wheate, N. J., Wang, S., D.P., Collins, J.G., Ralph, S.F., Day, A.I., Higgins, V.J. and Aldrich-Wright, J. R., J. Biol. Inorg. Chem., 12, 969-979 (2007).

11. “Dinuclear ruthenium(II) complexes with flexible bridges as non-duplex DNA binding agents.” Morgan, J.L., Spillane, C.B., Smith, J.A., Buck, P.D., Collins, J.G. and Keene, F.R., Dalton Trans., 4333-4342 (2007).

12. “DNA intercalators in cancer therapy: organic and inorganic drugs and their spectroscopic tools of analysis.” Wheate, N.J., Brodie, C.R., Collins, J.G., Kemp, S. and Aldrich-Wright, J. R., Mini-Reviews in Medicinal Chemistry, 7, 627-648 (2007).

13. “The effect of ancillary ligand chirality and phenanthroline functional group substitution on the cytotoxicity of platinum(II)-based metallointercalators.” Kemp, S., Wheate, N. J., Buck, D.P., Nikac, M., Collins, J.G. and Aldrich-Wright, J. R., J. Inorg. Biochem., 101, 1049-1058 (2007).

14. “ Cucurbituril binding of trans -[ {PtCl(NH 3)2}2 (m -NH2 (CH2 )8 NH2 )]2+ and the effect on the reaction with cysteine”, Bali , M.S., Buck, D.P., Coe, A.J. Day, A.I. and Collins, J.G., Dalton Trans., 5337-5344 (2006).

15. “ 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} ”, Morgan, J.L., Buck, P.D., Turley, A.G., Collins, J.G. and Keene, F.R., J. Biol. Inorg. Chem., 11, 824-834 (2006).

16. “ Meso -[ {Ru(phen)2 }2 ( m -HAT)]4+: a high-affinity DNA hairpin probe {HAT = 1,4,5,8,9,12-hexaazatriphenylene ; phen = 1,10-phenanthroline}, Smith, J.A., Morgan, J.L., Turley, A.G., Collins, J.G. and Keene, F.R., Dalton Trans., 3179-3187 (2006).

17. “Inert benzothiazol functionalised ruthenium(II) complexes; potential DNA hairpin binding agents”, Spillane, C.B., Morgan, J.L., Fletcher, N.C . , Collins, J.G. and Keene, F.R., Dalton Trans., 3122-3133 (2006).

18. “Cucurbit[n]uril binding of platinum anticancer complexes”, Wheate , N.J. , Buck, D.P., Day, A.I. and Collins, J.G., Dalton Trans., 451-458 (2006).

19. “Synthesis, Characterisation and Biological Activity of Chiral Platinum(II) Compounds”, Jaramillo, D.J., Collins, J.G., Buck, D.P., Fenton, R., Stootman, F. and Aldrich-Wright, J.R., Eur. J. Inorg. Chem., 839-849 (2006).

20. “ Meso -[{Ru(phen)2}2 ( m -bpm)]4+ : a high-affinity DNA bulge probe {bpm = 2,2'-bipyrimidine; phen = 1,10-phenanthroline} ”, J.L. Morgan, D.P. Buck, A.G. Turley, J.G. Collins and F.R. Keene, Inorg. Chim. Acta, 359, 888-898 (2006).

21. “Multi-nuclear platinum drugs: a new paradigm in chemotherapy”, Wheate, N.J. and Collins, J.G., Current Medicinal Chemistry-Anti-Cancer Agents, 5, 267-279 (2005).

22. “Potential adenine and minor groove binding platinum complexes”, Collins, J.G. and Wheate, N.J., J. Inorg. Biochem., 98, 1578-1584 (2004).

23. “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}”, Smith, J.A., Collins, J.G., Patterson, B.T. and Keene, F.R., Dalton Trans., 1277-1283 (2004).

24. “Multi-nuclear platinum complexes encapsulated in cucurbit[n]uril as an approach to reduce toxicity in cancer treatment “, Wheate, N.J., Day, A.I., Blanch, R.J., Arnold, A.P., Cullinane, C. and Collins, J.G., Chem. Commun., 1424-1425 (2004).

25. “The Structure Activity Relationship of Platinum(II) Intercalating Agents Containing Methyl-Substituted 1,10-Phenanthrolines”, Brodie, C.R., Collins, J.G. and Aldrich-Wright, J.R., Dalton Trans., 1145-1152 (2004).

26. “Multi-Nuclear platinum complexes as anti-cancer agents”, Wheate, N.J. and Collins, J.G., Coord. Chem. Rev., 241, 133-145 (2003).

27. “DNA binding of the anti-cancer platinum complex trans -[ {Pt(NH 3 )2 Cl}2 (m -dpzm)]2+”, Wheate, N.J., Evison, B.J., Herlt, A.J., Phillips, D.R and Collins, J.G., J. Chem. Soc., Dalton Trans., 3486-3492 (2003).

28. “Hydrolysis of Sesquimustards”, St Quintin, T.D., Leslie, D.R. and Collins, J.G., Aust. J. Chem., 56, 309-313 (2003).

29. “A web-based interactive homework quiz and tutorial package: Motivating undergraduate chemistry students”, Freasier, B., Collins, G. and Newitt, P., J. Chem. Ed., 80, 1344-1347 (2003).

30. “Dinuclear ruthenium(II) complexes as probes for DNA bulge sites”, Patterson, B.T., Collins, J.G., Foley, F.M. and Keene, F.R., J. Chem. Soc., Dalton Trans., 4343-4350 (2002).

31. “Minor groove intercalation of D -[Ru(Me2phen)2 (dppz)]2+ to the Hexanucleotide d(GTCGAC)2 ”, Greguric, A., Greguric I., Hambley, T.W., Aldrich-Wright, J.R. and Collins, J.G., J. Chem. Soc., Dalton Trans., 849-855 (2002).

32. “The binding of [(en)Pt( m -dpzm)2 Pt(en)]4+ to G/C Rich Regions of DNA”, Wheate , N.J., Cutts, S.M., Phillips, D.R., Aldrich-Wright, J.R. and Collins, J.G., J. Inorg. Biochem., 84, 119-127, (2001).

33. “Mass spectrometric studies of the path of carbon in photosynthesis: Positional isotopic analysis of 13 C-labelled C4 to C7 sugar phosphates”, MacLeod, J.K., Flanigan, I.L., Williams, J.F. and Collins, J.G., J. Mass Spectrometry, 36, 500-508, (2001).

34. “Thermal rearrangement of N-Substituted Pyrazoles to 4,4'-Dipyrazolylmethane and 1,1,2-(4,4',4”-Tripyrazolyl)ethane”, Wheate, N.J., Broomhead, J.A., Collins, J.G. and Day, A.I., Aust. J. Chem., 54, 141-144, (2001).

35. “The DNA binding of the DD - , DL - and LL -Stereoisomers of [ {Ru(Me 2 bpy)2 }2 (m -bpm)]4+ ”, Foley, F. M., Keene, F.R. and Collins, J.G., J. Chem. Soc. Dalton Trans., 2968-2974, (2001).

36. “Synthesis, cytotoxicity, cell uptake and interstrand cross-linking of dpzm linked platinum anti-cancer complexes”, Wheate, N.J., Cullinane, C., Webster, L.K and Collins, J.G., Anti-Cancer Drug Design, 16, 91-98, (2001).

37. “Interaction of [Pt(en)(phen)2+ and [Pt(en)(phi)]2+ with the hexanucleotide d(GTCGAC)2 : Evidence for minor groove binding”, Rixon, R.M., Aldrich-Wright, J.R. and Collins, J.G., Inorg. Chem., 39, 4377-4379, (2000).

38. “A 1 H NMR study of the oligonucleotide binding of [(en)Pt(m -dpzm)2 Pt(en)]Cl4 ”, Wheate , N.J. and Collins, J.G., J. Inorg. Biochem., 78, 313-321, (2000).

39. “Synthesis, DNA Binding and Cytotoxicity of Isohelical DNA Groove Binding Platinum Complexes”, Wheate , N.J. , Webster, L.K, Brodie, C.R, and Collins, J.G., Anti-Cancer Drug Design, 15, 313-322, (2000).