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US 2015/0032045 A1Published application
Photolabile compounds
AssigneesThe Trustees of Columbia University in the City of New York, University de Buenos Aires
InventorsRafael Yuste, Roberto Etchenique, Luis Baraldo
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Abstract
The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.
Claims73
A compound of Formula V:
- wherein:
- each L1 is independently an organic molecule having:
- (a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (h) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
- (d) an —NH2 group whose nitrogen atom forms a bond with Ru;
- (e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
- (f) a —PR2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- (g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- or
- (h) a —CN group whose nitrogen atom forms a bond with Ru;
- L2 is (R9)3P, (R9O)3P, or L1 and m is 2;
- or L2 is —CN and m is 1;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R9)2P or (R9 O)2P and m is 2;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of:
- NHR9, N(R9)2, pyridyl, C(R9)═NH, C(R9)═NR9 cyclic aliphatic amine group or nitrile and m is 2;
- wherein each R9 is independently —C1-C18 alkyl, —C3-C8 cycloalkyl, or phenyl;
- wherein when L2 is P(phenyl)3 or a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of P(phenyl)2, each phenyl is independently substituted with —C1-C18 alkyl, —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2Y, —C(═O)Y, —C(═O)NY2, —NH2, —NO2, —OH, or —SH, and
- R1 to R4 are independently —H, —C1-C18 alkyl;
- —NH2, —(C1-C18 alkyl)-O—(C1-C18 alkyl), —OC(O)(C1-C18 alkyl), —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2Y, —C(═O)Y, —C(═O)NY2, —NO2, or —SH, or R1 and R2 and/or R3 and R4 can combine to form a carbocyclic ring substituted by one or more oxo groups;
- wherein when L2 is not P(phenyl)3, R1 to R4 are independently —H, —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2Y, —C(═O)Y, —C(═O)NY2, —NO2, —OH, or —SH, or R1 and R2 and/or R3 and R4 can combine to form a carbocyclic ring substituted by one or more oxo groups, wherein at least one of R1 to R4 is not H;
- X is Cl−, F−, Br−, I−, PF6−, CF3SO3−, (C1-C18 alkyl)-CO2−, or (C1-C18 alkyl)-SO3−;
- and
- Y is selected from the group consisting of —H, —C1-C18 alkyl, aryl, —(C1-C18 alkyl)-aryl, —C3-C8 cycloalkyl, heteroaryl, and heterocyclyl.
21 more elements
A compound of Formula VI:
- wherein:
- each L1 is independently an organic molecule having:
- (a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (b) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
- (d) an —NH2 group whose nitrogen atom forms a bond with Ru;
- (e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
- (f) a —PR2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- (g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- or
- (h) a —CN group whose nitrogen atom forms a bond with Ru;
- L2 is P(phenyl)3, wherein each phenyl is independently substituted with —C1-C18 alkyl, —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2Y, —C(═O)Y, —C(═O)NY2, —NO2, —OH, or —SH;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R9)2P or (R9O)2P and m is 2;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of:
- NHR9, N(R9)2, pyridyl, C(R9)═NH, C(R9)═NR9 cyclic aliphatic amine group or nitrile and m is 2;
- wherein each R9 is independently —C1-C18 alkyl, —C3-C8 cycloalkyl, or phenyl;
- R1 to R4 are independently —H, —C1-C18 alkyl;
- —NH2, —(C1-C18 alkyl)-O—(C1-C18 alkyl), —OC(O)(C1-C18 alkyl), —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2Y, —C(═O)Y, —C(═O)NY2, —NO2, or —SH, or R1 and R2 and/or R3 and R4 can combine to form a carbocyclic ring substituted by one or more oxo groups;
- X is Cl−, F−, Br−, I−, PF6−, CF3SO3−, (C1-C18 alkyl)-CO2−, or (C1-C18 alkyl)-SO3−;
- and
- Y is selected from the group consisting of —H, —C1-C18 alkyl, aryl, —(C1-C18alkyl)-aryl, —C3-C8 cycloalkyl, heteroaryl, and heterocyclyl.
18 more elements
A compound of Formula VII:
- wherein:
- each L1 is independently an organic molecule having:
- (a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (b) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
- (c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
- (d) an —NH2 group whose nitrogen atom forms a bond with Ru;
- (e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
- (f) a —PR2 group whose phosphorus atom firms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- (g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C1-C18 alkyl, or aryl;
- or
- (h) a —CN group whose nitrogen atom forms a bond with Ru;
- L2 is (R9)3P, (R9O)3P, or L1, wherein each R5 is independently —C1-C18 alkyl, —C3-C8 cycloalkyl, or phenyl, m is 2, and L2 is not P(phenyl)3;
- or L2 is —CN and m is 1;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R9)2P or (R9O)2P and m is 2;
- or L2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of:
- NHR9, N(R9)2, pyridyl, C(R9)═NH, C(R9)═NR9 cyclic aliphatic amine group or nitrile and m is 2;
- wherein each R9 is independently —C1-C18 alkyl, —C3-C8 cycloalkyl, or phenyl;
- R1 to R4 are independently —H, —(C1-C18 alkyl)-OH, aryl, —(C1-C18 alkyl)-oxy, —(C1-C18 alkyl)-amino, —(C1-C18 alkyl)-thio, —CO2 Y, —C(═O)Y, —C(═O)NY2, —NO2, —OH, or —SH, or R1 and R2 and/or R3 and R4 can combine to form a carbocyclic ring substituted by one or more oxo groups, wherein at least one of R1 to R4 is not H;
- X is Cl−, F−, Br−, I−, PF6−, CF3SO3−, (C1-C18 alkyl)-CO2−, or (C1-C18 alkyl)-SO3−;
- and
- Y is selected from the group consisting of —H, —C1-C18 alkyl, aryl, —(C1-C18 alkyl)-aryl, —C3-C8cycloalkyl, heteroaryl, and heterocyclyl.
18 more elements
Dependencies are inferred from the claim text.