# US 8,148,360 B2 · Supramolecular metallic complexes exhibiting both DNA binding and photocleavage

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,148,360 B2
- Document ID: US8148360B2
- Status: Granted
- Kind: B2
- Application number: 11/851,689
- Filed: 2007-09-07
- Published: 2008-05-15
- Granted: 2012-04-03
- Earliest claimed: 2006-09-07
- Assignees: Virginia Tech Intellectual Properties, Inc.
- Inventors: Karen J. Brewer; Brenda Winkel
- Web page: https://patentgrep.com/patent/US8148360B2

## CPC

- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 41/0042: {Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion}
- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 47/558: {the modifying agent being a chemiluminescent acceptor}
- A61P 35/00: Antineoplastic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Supramolecular complexes that target and cleave DNA are provided. The supramolecular complexes include at least one metal-to-ligand charge transfer (MLCT) light absorbing unit, at least one Pt based DNA binding unit, and at least one bridging unit that serves to connect the components. The Pt-based DNA binding unit binds the complex to DNA, and the MLCT unit absorbs light, thereby sensitizing molecular oxygen to produce reactive oxygen species in close proximity to the complex and the bound DNA. The reactive oxygen species cleave the bound DNA.

## Claims

### Claim 1

A supramolecular complex comprising
at least one metal to ligand charge transfer (MLCT) light absorbing metal,
at least one bridging ligand selected from the group consisting of 2,3-bis(2-pyridyl) pyrazine,2,2′-bipyridimidine, 2,3,-bis(2-pyridyl)quinoxaline, and 2,3,5,6-tetrakis(2-pyridyl)pyrazine, and
at least one Pt based DNA binding unit which is cis PtCl2.

### Claim 2 (depends on 1)

The supramolecular complex of claim 1 wherein said at least one metal to ligand charge transfer (MLCT) light absorbing metal is selected from the group consisting of ruthenium(II), osmium(III), rhenium(I), iron(II) and platinum(II).

### Claim 3 (depends on 1)

The supramolecular complex of claim 1, wherein said supramolecular complex further comprises at least one terminal ligand.

### Claim 4 (depends on 3)

The supramolecular complex of claim 3, wherein said at least one terminal ligand is a π-acceptor ligand.

### Claim 5 (depends on 3)

The supramolecular complex of claim 3, wherein said at least one terminal ligand is selected from the group consisting of 2,2′-bipyridine; 2,2′:6′,2″-terpyridine; triphenylphosphine; and 2,2′-phenylpyridine and diethylphenylphosphine.

### Claim 6 (depends on 1)

The supramolecular complex of claim 1, further comprising a counterion.

### Claim 7 (depends on 6)

The supramolecular complex of claim 6, wherein said counterion is selected from the group consisting of PF6−, Cl−, Br−,I−, CF3SO3−, BF4−, NO3−, CLO4−, CO3−2, SO42−.

### Claim 8 (depends on 1)

The supramolecular complex of claim 1 wherein said supramolecular complex is selected from the group consisting of
[{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpq)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpb)PtCl2](PF6)6, [{(phen)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6 and [{(bpy)2Os(dpp)}2Ru(dpq)PtCl2](PF6)6.

### Claim 9

A method for cleaving DNA comprising the steps of
combining said DNA with a supramolecular complex comprising
at least one metal to ligand charge transfer (MLCT) light absorbing metal,
at least one bridging ligand selected from the group consisting of 2,3-bis(2-pyridyl)pyrazine, 2,2′-bipyridimidine, 2,3,-bis(2-pyridyl) quinoxaline, and 2,3,5,6-tetrakis(2-pyridyl)pyrazine, and
at least one Pt based DNA binding unit which is cis PtCl2,
said combining being carried out in the presence of molecular oxygen and under conditions that allow said at least one Pt based DNA binding unit to bind to said DNA; and
exposing said DNA to light or radiant energy in a quantity sufficient to cause sensitization of said molecular oxygen by said MLCT light absorbing metal, thereby forming a reactive oxygen species that cleaves said DNA.

### Claim 10 (depends on 9)

The method of claim 9 wherein said at least one metal to ligand charge transfer (MLCT) light absorbing metal is selected from the group consisting of ruthenium(II), osmium(III), rhenium(I), iron(II) and platinum(II).

### Claim 11 (depends on 9)

The method of claim 9, wherein said supramolecular complex further comprises at least one terminal ligand.

### Claim 12 (depends on 11)

The supramolecular complex of claim 11, wherein said at least one terminal ligand is a π-acceptor ligand.

### Claim 13 (depends on 11)

The method of claim 11, wherein said at least one terminal ligand is selected from the group consisting of 2,2′-bipyridine; 2,2′:6′,2″-terpyridine; triphenylphosphine; and 2,2′-phenylpyridine and diethylphenylphosphine.

### Claim 14 (depends on 9)

The method of claim 9 wherein said light is visible light.

### Claim 15 (depends on 9)

The method of claim 9, wherein said supramolecular complex further comprises a counterion.

### Claim 16 (depends on 15)

The supramolecular complex of claim 15, wherein said counterion is selected from the group consisting of PF6−, Cl−, Br−, I−, CF3SO3−, BF4−, NO3−, CLO4−, CO3−2, SO42−.

### Claim 17 (depends on 9)

The method of claim 9 wherein said supramolecular complex is selected from the group consisting of [{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpq)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpb)PtCl2](PF6)6, [{(phen)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6and [{(bpy)2Os(dpp)}2Ru(dpq)PtCl2](PF6)6.

### Claim 18 (depends on 9)

The method of claim 9 wherein said combining step occurs within a hyperproliferating cell.

### Claim 19

A composition for effecting the cleavage of DNA in hyperproliferating cells, comprising,
a supramolecular complex comprising
at least one metal to ligand charge transfer (MLCT) light absorbing metal;
at least one bridging ligand selected from the group consisting of 2,3-bis(2-pyridyl)pyrazine, 2,2′-biyridimidne, 2,3,-bis(2-pyridyl) quinoxaline, and 2,3,5,6-tetrakis(2-pyridyl)pyarzine;
at least one Pt based DNA binding unit which is cis PtCl2; and a carrier.

### Claim 20 (depends on 19)

The composition of claim 19 wherein said at least one metal to ligand charge transfer (MLCT) light absorbing metal is selected from the group consisting of ruthenium(II), osmium(III), rhenium(I), iron(II) and platinum(II).

### Claim 21 (depends on 19)

The composition of claim 19, wherein said supramolecular complex further comprises at least one terminal ligand.

### Claim 22 (depends on 21)

The composition of claim 21, wherein said at least one terminal ligand is a π-acceptor ligand.

### Claim 23 (depends on 21)

The composition of claim 21, wherein said at least one terminal ligand is selected from the group consisting of 2,2′-bipyridine; 2,2′:6′,2″-terpyridine; triphenylphosphine; and 2,2′-phenylpyridine and diethylphenylphosphine.

### Claim 24 (depends on 19)

The composition of claim 19 further comprising a carrier, said supramolecular complex being dissolved or dispersed in said carrier.

### Claim 25 (depends on 19)

The composition of claim 19, wherein said supramolecular complex further comprises a counterion.

### Claim 26 (depends on 25)

The supramolecular complex of claim 25, wherein said counterion is selected from the group consisting of PF6−, Cl−, Br−, I−, CF3SO3−, BF4−, NO3−, CLO4−, CO3−2, SO42−.

### Claim 27 (depends on 19)

The composition of claim 19 wherein said supramolecular complex is selected from the group consisting of [{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpq)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpb)PtCl2](PF6)6, [{(phen)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6 and [{(bpy)2Os(dpp)}2Ru(dpq)PtCl2](PF6)6.

### Claim 28

A method for decreasing the replication of hyperproliferating cells, comprising the steps of
delivering to said cells a supramolecular complex comprising
at least one metal to ligand charge transfer (MLCT) light absorbing metal;
at least one bridging ligand selected from the group consisting of 2,3-bis(2-pyridyl)pyrazine, 2,2′-bipyridimidine, 2,3,-bis(2-pyridyl) quinoxaline, and 2,3,5,6-tetrakis(2-pyridyl)pyrazine; and
at least one Pt based DNA binding unit which is cis PtCl2; and
applying light or radiant energy to said hyperproliferating cells, wherein said step of applying light to said hyperproliferating cells induces sensitization of said molecular oxygen by said MLCT light absorbing metal, thereby forming a reactive oxygen species that cleaves said DNA of said hyperproliferating cells, thereby causing a decrease in the replication of said hyperproliferating cells.

### Claim 29 (depends on 28)

The method of claim 28, wherein said at least one metal to ligand charge transfer (MLCT) light absorbing metal is selected from the group consisting of ruthenium(II), osmium(III), rhenium(I), iron(II) and platinum(II).

### Claim 30 (depends on 28)

The method of claim 28, wherein said supramolecular complex further comprises at least one terminal ligand.

### Claim 31 (depends on 30)

The method of claim 30, wherein said at least one terminal ligand is a π-acceptor ligand.

### Claim 32 (depends on 30)

The method of claim 30, wherein said at least one terminal ligand is selected from the group consisting of 2,2′-bipyridine; 2,2′:6′,2″-terpyridine; triphenylphosphine; and 2,2′-phenylpyridine and diethylphenylphosphine.

### Claim 33 (depends on 28)

The method of claim 28 wherein said light is visible light.

### Claim 34 (depends on 28)

The method of claim 28, wherein said supramolecular complex further comprises a counterion.

### Claim 35 (depends on 34)

The supramolecular complex of claim 34, wherein said counterion is selected from the group consisting of PF6−, Cl−, Br−, I−, CF3SO3−, BF4−, NO3−, CLO4−, CO3−2, SO42−.

### Claim 36 (depends on 28)

The method of claim 28 wherein said supramolecular complex is selected from the group consisting of [{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpq)PtCl2](PF6)6, [{(bpy)2Ru(dpp)}2Ru(dpb)PtCl2](PF6)6, [{(phen)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6 and [{(bpy)2Os(dpp)}2Ru(dpq)PtCl2](PF6)6.

### Claim 37 (depends on 28)

The method of claim 28 wherein said hyperproliferating cells are cancer cells.