Synthesis, photophysical and electrochemical properties, and protein-binding studies of luminescent cyclometalated Iridium(III) bipyridine estradiol conjugates

A new series of luminescent cyclometalated iridium(III) bipyridine estradiol conjugates [Ir(N-C)(2)(N-N)](PF6) (N-N = 5-(4-(17 alpha-ethynylestradiolyl)phenyl)-2,2'-bipyridine, bpy-est, HN-C = 2-phenylpyridine, Hppy (1a), 1-phenylpyrazole, Hppz (2a), 7,8-benzoquinoline, Hbzq (3a), 2-phenylquinoline, Hpq (4a), 2-((1,1'-biphenyl)-4-yl)benzothiazole, Hbsb (5a); N-N = 4-(N-(6- (4-(17 alpha-ethynyl estradiolyl) benzoylamino)hexyl)aminocarbonyl)-4'- methyl-2,2'-bipyridine, bpy-C6-est, HNC = Hppy (1b), Hppz (2b), Hbzq (3b), Hpq (4b), Hbsb (5b)) was synthesized, characterized, and their photophysical and electrochemical properties studied. Upon photoexcitation, all the complexes displayed intense and long-lived emission in fluid solutions at 298 K and in low-temperature glass. The emission of complexes 1a-3a and 1b-3b was assigned to a triplet metal-to-ligand charge-transfer ((MLCT)-M-3) (d pi(Ir)->pi*(bpy-est and N-C-)) state mixed with some triplet intraligand ((IL)-I-3) (pi ->pi*) (N-C- and N-N) character. However, the emissive states of the pq(-) and bsb(-) complexes 4a, 4b, 5a, and 5b showed substantial (IL)-I-3 (pi ->pi*) (pq(-)/bsb(-)) character. The lipophilicity of all the complexes was determined by reversed-phase HPLC. Upon binding to estrogen receptor a., all of these iridium(III) estradiol conjugates exhibited emission enhancement and lifetime extension, rendering them a novel series of luminescent probes for this receptor.