Reaction-based fluorescent probe for selective detection of carbon monoxide using metal-mediated carbonylation

摘要

Carbon monoxide (CO) is a member of the gasotransmitter family that includes NO and H2S and is implicated in a variety of pathological and physiological conditions. Whereas exogenous therapeutic additions of CO to tissues and whole animals have been well studied, the real-time spatial and temporal tracking of CO at the cellular level remains an open challenge. We now report a new type of turn-on fluorescent probe for selective CO detection by exploiting palladium-mediated carbonylation reactivity. The compounds of the invention are capable of detecting CO both in aqueous buffer and in live cells with high selectivity over a range of biologically relevant reactive small molecules, providing a potentially powerful approach for interrogating its chemistry in biological systems.

主权项

1. A fluorogenic compound, which is a probe for CO, and which detectably fluoresces upon carbonylation with CO, said probe having a structure according to Formula I: wherein,
M is a metal capable of catalyzing carbonylation by CO of the ring system to which it is bound, said metal optionally bound to one, two or more additional ligands;the dashed line (- - - -) indicates a degree of unsaturation that is either present or absent;X is a moiety selected from the group consisting of NR6R7, NR6, PR6R7 and SR6 wherein,
R6 and R7 are members independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, and R6 and R7, together with the atoms to which they are bound are optionally joined to form a 5- to 7-membered ring system which is a member selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;R1, R2, R3, R4, and R5 are members independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, halogen, CN, CF3, acyl, —SO2NR12R13, —NR12R13, —OR12, —S(O)2R12, —C(O)R12, —COOR12, —CONR12R13, —S(O)2OR12, —OC(O)R12, —C(O)NR12R13, —NR12C(O)R13, —NR12SO2R13, NR12C(O)NR13R14, C(NR12)R13, and —NO2, and at least one of R1, R2, R3, and R4 is a fluorophore, wherein said fluorophore is maintained in a quenched state by interacting with M, wherein,
R12, R13 and R14 are members independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, and two or more of R12, R13, and R14, together with the atoms to which they are bound, are optionally joined to form a 5- to 7-membered ring system which is a member selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, andtwo or more of R1, R2, R3, R4, and are optionally joined to form a 5-7-membered ring system selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl with the proviso that if two or more of R1, R2, R3, R4, and R5 are joined to form said ring system, then none of said two or more of R1, R2, R3, R4, and R5 so joined are said fluorophore; wherein said fluorophore has the formula: wherein R31, R32, R33, R34, R35, R36 and R37 are members independently selected from the group consisting of H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein at least one of R31, R32, R33, R34, R35, R36 and R37 comprises a bond to the remainder of the compound according to Formula I; and R38 and R39 are members independently selected from the group consisting of H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and NR40R41 wherein R40 and R41 are members independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.