US005112974A
United States Patent [19] [li] Patent Number: 5,112,974
Barton [45] Date of Patent: May 12, 1992
[54] MIXED LIGAND COMPLEXES AND USES THEREOF AS BINDING AGENTS TO DNA
[75] Inventor: Jacqueline K. Barton, New York. N.Y.
[73] Assignee: The Trustees of Columbia University in the Citv of New York, New York, N.Y.
[21] Appl. No.: 268,247
[22] Filed: Nov. 7, 1988
Related U.S. Application Data
[63] Continuation-in-parl of Ser. No. 905.295. Sep. 8. 1986. which is a continuation-in-part of Ser. No. 693,023. Jan. 18. 1985. Pat. No. 4.721.669.
[51] Int. CI.? C07F 15/00; OPD 471.04:
A61K 33/24: A61K 31/555
[52] U.S. CI. 546/4; 546/10:
546/88: 546/275; 556/136: 556/138: 424/9; 424/11: 424/617; 424/641; 424/646: 424/652: 935/77; 935/88; 204/157.72
[58] Field of Search 546/81. 84. 88. 4. 10.
546/275; 534/15: 556/136. 138: 424/9. 11. 641.
617. 646. 652: 935/77. 78: 204/157.22
[56] References Cited
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26:3820-3823.
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Mei. H-Y and Barton, J. K.. Proc. Natl Acad. Sci. USA 1988; 85:1339-1343.
Baum, R. M., C&EN, pp. 22-25. Jun. 12, 1989.
Primary Examiner—Cecilia Shen
Attorney, Agent, or Firm—John P. White
[57] ABSTRACT
This invention concerns a coordination complex or salt thereof which is spectroscopically or photoactively determinable when bound to DNA having the formula
I
Rl — M — Rj.
wherein M is a suitable transition metal and each of Rj, Rt and R? is ethylenediamine. bipyridine, phenanthroline. diazafluorene-9-one or phenanthrenequinonediimine. In the complex, R\, Ri and R3 are bound to M by coordination bonds and Ri and R2 may be the same or different and both are different from R3. In the preferred embodiments, the invention concerns complexes of ruthenium(Ru) or rhodium(Rh) wherein Ri and R2 are the same. The invention also concerns the complex
R
I
R—M —R.
wherein M is Ru or Rh and R is 9-10-phenanthrenequinonediimine or 5-nitrophenanthroline.
25 Claims, 28 Drawing Sheets
