Supramolecular metallic complexes exhibiting both DNA binding and photocleavage
AssigneeVirginia Tech Intellectual Properties, Inc.
InventorsKaren J. Brewer, Brenda Winkel
Life of this patent
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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.
Claims37
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.
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.
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.
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.
Dependencies are inferred from the claim text.