Luminescent Tricarbonylrhenium(I) Polypyridine Estradiol Conjugates:  Synthesis, Crystal Structure, and Photophysical, Electrochemical, and Protein-Binding Properties

Abstract

A series of luminescent tricarbonylrhenium(I) polypyridine estradiol complexes [Re(N-N)(CO) 3 (L)]-(CF 3 SO 3 ) (N-N ) 1,10-phenanthroline (phen), L ) 4-(17R-ethynylestradiolyl)pyridine (py-est) (1a), 4-(N-(6-(4-(17R-ethynylestradiolyl)benzoylamino)hexanoyl)aminomethyl)pyridine (py-C6-est) (1b); N-N ) 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 -phen), L ) py-est (2a), py-C6-est (2b); N-N ) 4,7diphenyl-1,10-phenanthroline (Ph 2 -phen), L ) py-est (3a), py-C6-est (3b)) have been synthesized and characterized. The X-ray crystal structure of complex 1a has also been investigated. The photophysical and electrochemical properties of all the complexes have been studied. Upon irradiation, most of the complexes exhibited intense and long-lived triplet metal-to-ligand charge-transfer ( 3 MLCT) (dπ(Re) f π*(N-N)) emission in fluid solutions at 298 K and in low-temperature glass. The excited states of the Me 4 -phen complexes possessed some triplet intraligand 3 IL character. The lipophilicity of all the complexes has been determined by reversed-phase HPLC. In addition, the binding of these complexes to estrogen receptor R has been investigated by emission titrations.

Synthesis, Photophysical and Electrochemical Properties, and Protein‐Binding Studies of Luminescent Cyclometalated Iridium(III) Bipyridine Estradiol Conjugates

“…Nevertheless, the binding constants of all the complexes are comparable to or larger than those of other related estradiol derivatives such as 17a-[(L)Re(CO) 3 ]-estra- , respectively), [5] 17a- , respectively), [6] and [ReA C H T U N G T R E N N U N G (N-N)(CO) 3 (py-C6-est)]A C H T U N G T R E N N U N G (CF 3 SO 3 ) (py-C6-est = 4-(N- (6-(4-(17a-ethynylestradiolyl)benzoylamino)hexanoyl)aminomethyl)pyridine) (1.5 to 2.0 10 7 m À1 ). [16] The intrinsic increase in emission intensities of the complexes upon binding to the receptor is moderate (about 1.3 to 4.8 times, Table 5). To develop homogeneous assays for ERa, it is desirable to maximize the difference in emission intensities between the free and protein-bound forms of the iridiumA C H T U N G T R E N N U N G (III) estradiol complexes.…”

“…[16] In particular, due to the largest difference in K SV in the absence and presence of ERa, the emission intensity of complex 4 a was substantially increased by about 49 times upon binding to the biological receptor (Table 6 and Figure 7), rendering it to serve as a "light switch" for this protein. These interesting changes in the photophysical properties of the luminescent iridiumA C H T U N G T R E N N U N G (III) estradiol complexes upon binding to ERa, together with the reasonably strong binding affinities, indicate that they act as effective luminescent probes for this biological receptor and are useful in the development of new homogeneous bioassays.…”

“…[2] Owing to the important roles of both estradiol and its receptor in female physiology, the design of new biological probes for estradiol-binding proteins has attracted much attention. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Radioactive hormone derivatives, such as those containing tritium [3,4] and technetium, [5,6] are the most frequently used reagents. However, the potential health hazards of these reagents and the long experimental time required have prompted the search for nonisotopic reagents.…”

“…[5, 15a,c,d ,f-h] Recently, we studied the interactions of luminescent rhenium(I) polypyridine estradiol complexes with estrogen receptors; binding of the complexes to the biomolecules leads to an enhancement of their emission intensities of between five-and sixfold. [16] Our current aim is to design new probes with more favorable emission properties and higher sensitivity. In view of the interesting emissive behavior of iridiumA C H T U N G T R E N N U N G (III) polypyridine complexes, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] in particular their high environment-sensitivity, diverse emissive-state character due to a wide choice of both cyclometalating and diimine ligands, and our interest in using these complexes as biological labels and probes, [33] we believe that cyclometalated iridiumA C H T U N G T R E N N U N G (III) polypyridine estradiol conjugates have a high potential to serve as new luminescent probes for estrogen receptors.…”

“…7.27-7.18 (m, 12 H; H5, H6 benzothiazole Physical measurements and instrumentation: Equipment for the characterization and photophysical, electrochemical, and lipophilicity measurements has been described previously. [16] Luminescence quantum yields were measured by the optically dilute method [44] using an aerated aqueous solution of [RuA C H T U N G T R E N N U N G (bpy) 3 ]Cl 2 (F = 0.028) as the standard solution. [45] Emission titrations: The iridiumA C H T U N G T R E N N U N G (III) complex (10 nmol) dissolved in methanol (200 mL) was added to a series of potassium phosphate buffer solutions (1.8 mL, 50 mm, pH 7.4) containing ERa.…”