Dual-sensitizer-containing luminescent compounds, conjugates, and uses thereof

A method of detecting a target with a probe, the method comprising:

• contacting a sample with, or delivering to a subject, a luminescent probe composition comprising a targeting-probe moiety having an affinity for a target, the targeting-probe moiety covalently conjugated to a luminescent chelate composition comprising:
• (i) a first sensitizer moiety;
• (ii) a chelating moiety covalently joined, optionally through a first linker, to the first sensitizer;
• and
• (iii) a second sensitizer moiety covalently joined, optionally through a second linker, to the chelating moiety of (ii);
• wherein, the first and second sensitizer moieties, independently, have the Formula (I) or the Formula (II), wherein Formula (I) is:
• and wherein:
• X is CH—R1, O, S, or N—R1;
• R1 is H;
• a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• R2 is H;
• NH2;
• carboxamide;
• hydrazide;
• acylhydrazide or alkylhydrazide;
• hydroxamate;
• COOH;
• CO—R′ or CO—O—R′, where R′ is a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• R3 is a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene, or alkylarene moieties are optionally further substituted with from 1-3 halo atoms;
• and
• wherein the
• at position 7 of the phenyl ring indicates the site of covalent attachment, optionally through a linker, of the sensitizer moiety to the chelating moiety;
• and
• wherein Formula (II) is:
• and wherein:
• Z is CH—R4, O, S, or N—R4;
• R4 is H;
• a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene, alkylarene moieties are optionally further substituted with from 1-3 halo atoms;
• R5 is carboxamide;
• hydrazide;
• acylhydrazide or alkylhydrazide;
• hydroxamate;
• COOH;
• CO—R′ or CO—O—R′, where R′ is a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• and
• R6 is H;
• a halogen;
• a linear alkylene (C1-C20), a branched alkylene (C3-C20), a cyclic alkylene (C3-C10), a linear alkenylene (C2-C20), a branched alkenylene (C3-C20), a cyclic alkenylene (C3-C10), a linear alkynylene (C2-C20), a branched alkynylene (C3-C20), a cyclic alkynylene (C3-C10), an arene (C6-C19), an alkylarene having a C1-C20 alkyl portion and a C6-C19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
• and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene or alkylarene moieties are optionally further substituted with from 1-3 halo atoms;
• and
• wherein the
• at position 7 of the phenyl ring indicates the site of covalent attachment, optionally through a linker, of the sensitizer moiety to the chelating moiety;
• and
• wherein the chelating moiety is selected from the group consisting of:
• EDTA, DTPA, TTHA, DOTA, TAGA, DOTP, DTPA-BMA, DO2P, and HP-DO3A;
• and
• wherein one of the sensitizer moieties is covalently linked at the R2 or R5 position, optionally through a third linker moiety, to a conjugating group;
• and
• wherein the luminescent composition further comprises a lanthanide chelated to the chelating moiety, the lanthanide selected from the group consisting of:
• Gd(III), Dy(III), Ho(III), Er(III), Eu(III), Tb(III), Sm(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV);
• and
• detecting a signal produced from the luminescent probe composition.