Method of targeting mismatched DNA using d8 square planar metal complexes

1. A method to target mismatched DNA, the method comprising

bringing into contact a DNA sample comprising pairing nucleobases and/or non-pairing nucleobases and a d 8 square planar metal complex, and

detecting the emission of the complex intercalated into DNA in the sample,

wherein emission above a threshold level indicates the presence of mismatched DNA in the sample, wherein the threshold level is the emission from a metal complex intercalated into a well-matched DNA, and

wherein the complex has a structure according to Formula I or Formula II:

wherein:

X^Y^Z and X′^Y′^Z′ are each, independently, a tridentate π-conjugated ligand;

X, Y, Z, X′, Y′, and Z′ are each, independently, carbon or nitrogen;

R, R′, and R″ are each, independently, a N-heterocyclic carbene ligand or a phosphine ligand;

each M is a d 8 metal atom;

n is the charge of the complex;

A is the counter-ion for the complex;

b is the charge of the counter-ion; and

y is the absolute value of n/b.

2. The method of claim 1 , in which the complex has a structure according to Formula I-A:

wherein:

M is Au, Pt, or Pd;

R 1 is hydrogen or phenyl;

R 2 and R 3 are each hydrogen or together are —CH—CH—CH—CH—;

R 4 , R 5 , R 7 , and R 8 are each hydrogen;

R 6 and R 9 are each independently selected from —CH 3 , —C 2 H 5 , —C 3 H 7 , —C 4 H 9 , —C 5 H 11 , C 6 H 13 , benzyl, (2-hydroxy) ethyl, phenyl, naphthalen-2-ylmethyl, or (2-phenyl) ethyl;

n is +1 or +2; and

X, Y, Z are each independently carbon or nitrogen.

3. The method of claim 2 , in which:

M is Platinum;

R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , and R 8 are each hydrogen;

R 6 is benzyl;

R 9 is —C 4 H 9 ;

n is +1;

yA b is CF 3 SO 4 − ;

X is carbon; and

Y and Z are each nitrogen.

4. The method of claim 2 , in which the complex has a structure according to Formula I, wherein M is coordinated to an anionic or di-anionic 1,3-di(pyridin-2-yl)benzene (N^C^N) ligand, 2,6-diphenylpyridine (C^N^C) ligand, 6-phenyl-2,2′-bipyridine (C^N^N) ligand, 6-(naphthalen-2-yl)-2,2′-bipyridine ligand, 4,6-diphenyl-2,2′-bipyridine ligand, or a N-heterocyclic carbene ligand.

5. The method as in claim 1 , in which each M is, independently, platinum(II) (Pt(II) or Pt 2+ ), palladium(II) (Pd(II) or Pd 2+ ), or gold(III) (Au(III) or Au 3+ ).

6. The method as in either claim 1 or 2 , in which the non-pairing nucleobases are selected from the group consisting of: adenine/adenine (A/A), adenine/guanine (A/G), adenine/cytosine (A/C), guanine/guanine (G/G), guanine/thymine (G/T), thymine/cytosine (T/C), thymine/thymine (T/T), and cytosine/cytosine (C/C) nucleobases.

7. The method as in either claim 1 or 2 , in which detecting the emission of the complex intercalated into DNA in the sample is selected from the group consisting of: emission spectroscopy, UV-Vis absorption spectroscopy, isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR) spectroscopy.

8. The method of claim 1 , in which the complex has a structure according to Formula II, wherein the two M are each coordinated to an anionic 6-phenyl-2,2′-bipyridine (C^N^N) ligand and are connected with bis-N-heterocyclic carbene or diphosphine ligand.

9. The method of claim 1 , in which the mismatched DNA comprises DNA containing one or more non-pairing nucleobases.

10. The method of claim 1 , in which R′^R″ is a bis-N-heterocyclic carbene or diphosphine ligand.

11. The method as in either claim 1 or 10 , in which the complex has a structure according to Formula II-A:

wherein:

each M is independently selected from Au, Pt, or Pd;

R 2 , R 3 , R 4 , and R 5 are each hydrogen;

R 1 and R 6 are each independently selected from —CH 3 , benzyl, or naphthalen-2-ylmethyl;

n is +1 or +2;

y is equal to the absolute value of n/b; and

each X, Y, and Z are independently carbon or nitrogen.

12. The method of claim 1 , in which:

each M is Platinum;

R 2 , R 3 , R 4 , and R 5 are each hydrogen;

R 1 and R 6 are each benzyl;

n is +2;

yAb is 2 CF 3 SO 3 − ;

each X is carbon, and

each Y and Z is nitrogen.

13. The method of claim 1 , in which the DNA sample comprises a cell of a subject, wherein emission above a threshold level indicates that the cell is a cancer cell.

14. The method of claim 13 , further comprising treating the subject with an anti-cancer therapy.

15. The method of claim 1 , in which the complex has a structure according to Formula II-B:

wherein:

each M is independently selected from Au, Pt or Pd;

R 1 , R 2 , R 3 , and R 4 are each independently selected from phenyl or C 6 H 6 ;

n is +1 or +2;

y is equal to the absolute value of n/b; and

each X, Y, and Z are independently carbon or nitrogen.

16. The method of claim 15 , in which:

each M is Platinum;

R 1 , R 2 , R 3 , and R 4 are each phenyl;

n is +2;

yAb is 2 CF 3 SO 3 − ;

each X is carbon, and

each Y and Z is nitrogen.

17. The method as in claim 2 , in which each M is, independently, platinum(II) (Pt(II) or Pt 2+ ), palladium(II) (Pd(II) or Pd 2+ ), or gold(III) (Au(III) or Au 3+ ).

18. The method as in claim 2 , in which the non-pairing nucleobases are selected from the group consisting of: adenine/adenine (A/A), adenine/guanine (A/G), adenine/cytosine (A/C), guanine/guanine (G/G), guanine/thymine (G/T), thymine/cytosine (T/C), thymine/thymine (T/T), and cytosine/cytosine (C/C) nucleobases.

19. The method as in claim 2 , in which detecting the emission of the complex intercalated into DNA in the sample is selected from the group consisting of: emission spectroscopy, UV-Vis absorption spectroscopy, isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR) spectroscopy.

20. The method as in claim 10 , in which the complex has a structure according to Formula II-A:

wherein:

each M is independently selected from Au, Pt, or Pd;

R 2 , R 3 , R 4 , and R 5 are each hydrogen;

R 1 and R 6 are each independently selected from —CH 3 , benzyl, or naphthalen-2-ylmethyl;

n is +1 or +2;

y is equal to the absolute value of n/b; and

each X, Y, and Z are independently carbon or nitrogen.