Man-Wai Louie

Luminescent rhenium(I) polypyridine complexes appended with an α-D-glucose moiety as novel biomolecular and cellular probes.

Glucose is the most important carbohydrate in cellular metabolism and an energy source for the growth of cells. One of the most characteristic phenotypes of rapidly growing cancer cells is their propensity to catabolize glucose at high rates, possibly due to the overexpression of glucose transporters (GLUTs). Thus, the in vitro and in vivo monitoring of glucose utilization in cancer cells has attracted much attention. Different reporting and therapeutic units such as radioactive labels, IRDye 800CW, organic fluorophores, and two-photon dyes have been conjugated to glucose or 2-deoxyglucose for the diagnosis and treatment of various tumors or cancers. Despite the development of these reagents, the possibility of using luminescent transition-metal glucose conjugates as glucoseuptake tracers and cancer cell imaging reagents has not been explored. With our ongoing interest in luminescent rhenium(I) polypyridine complexes as biological probes, we envisage that modification of these complexes with an ad-glucose pendant will generate useful luminescent probes for biomolecules and cancer cells. Herein we report three rhenium(I) polypyridine glucose complexes [Re ACHTUNGTRENNUNG(N^N)(CO)3ACHTUNGTRENNUNG(py-3-glu)] ACHTUNGTRENNUNG(PF6) (py-3-glu =3(N-(6-(N’-(4-(a-d-glucopyranosyl)phenyl)thioureidyl)hexyl)thioureidyl)pyridine, N^N=1,10-phenanthroline (phen) (1), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3)) and their glucose-free counterparts [Re ACHTUNGTRENNUNG(N^N)(CO)3ACHTUNGTRENNUNG(py-3-Et)]ACHTUNGTRENNUNG(CF3SO3) (py-3-Et=3-(ethylthioureidyl)pyridine, N^N= phen (1 a), Me4-phen (2 a), Ph2-phen (3 a)) (Scheme 1). The glucose complexes were synthesized from the addition reaction of the isothiocyanate complexes [Re ACHTUNGTRENNUNG(N^N)(CO)3ACHTUNGTRENNUNG(py-3NCS)] ACHTUNGTRENNUNG(PF6)[5a] with AcO-glu-C6-NH2 in acetone, followed by deacetylation (see the Supporting Information, Schemes S1 and S2). All the complexes were characterized by H NMR spectroscopy, positive-ion ESI-MS, and IR spectroscopy and gave satisfactory elemental analyses (see the Supporting Information). Upon irradiation, the complexes exhibited intense and long-lived green-to-yellow triplet metal-to-ligand charge-transfer (MLCT; dp(Re)!p* ACHTUNGTRENNUNG(N^N)) emission (see the Supporting Information, Table S1). The structured emission band and very long lifetime of complex 2 in alcohol glass at 77 K are probably due to the involvement of IL (p!p*) (Me4-phen) character in its emissive state. Since the lectin concanavalin A (Con A) binds a-d-mannopyranoside and a-d-glucopyranoside, the possible use of the glucose complexes 1–3 as a luminescent sensor for this lectin has been investigated. Upon addition of Con A to a [a] M.-W. Louie, Dr. H.-W. Liu, M. H.-C. Lam, Dr. Y.-W. Lam, Dr. K. K.-W. Lo Department of Biology and Chemistry City University of Hong Kong, Tat Chee Avenue Kowloon, Hong Kong (P.R. China) Fax: (+852) 3442-0522 E-mail : bhkenlo@cityu.edu.hk Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101399. Scheme 1. Structures of the rhenium(I) polypyridine complexes.

Induced self-assembly and disassembly of water-soluble alkynylplatinum(II) terpyridyl complexes with “switchable” near-infrared (NIR) emission modulated by metal–metal interactions over physiological pH: demonstration of pH-responsive NIR luminescent probes in cell-imaging studies

Water-soluble alkynylplatinum(II) terpyridine complexes, [Pt{tpy(C6H4CH2NMe3-4)-4′}(CC–Ar)](OTf)2 [Ar = C6H3–(OH)2-3,5 (1), C6H4OH-4 (2), C6H3–(OMe)2-3,5 (3)], have been synthesized and characterized. The photophysical and electrochemical properties of the complexes have been studied. Complex 1 has been found to undergo aggregation at low pHs, leading to metal–metal and/or π–π interactions and the emergence of a triplet metal-metal-to-ligand charge transfer (3MMLCT) emission in the near-infrared (NIR) region, the intensity of which has been enhanced 1350-fold over that at physiological pH. Such ‘switchable’ NIR emission of complex 1 was employed in cell-imaging experiments. The pH response of the 3MMLCT emission of complex 1 in cellular compartments has been studied using experiments with fixed Madin–Darby canine kidney (MDCK) cells, while live cell-imaging experiments revealed that complex 1 could function as a NIR luminescent probe for the tracking of the location of acidic organelles such as lysosomes.

Luminescent rhenium(I) polypyridine fluorous complexes as new biological probes

We present the synthesis and characterization of luminescent biological probes derived from rhenium(I) polypyridine fluorous complexes [Re(Me2 bpy)(CO)3(py-Rf-R)](PF6) (R = NH2 (1), NCS (2), TU-C2H5 (3)). The photophysical properties of these complexes have been studied. The fluorous complex 2 has been used to label glutathione (GSH) and bovine serum albumin (BSA). The photophysical properties of the resultant bioconjugates have been studied. The isolation of the luminescent fluorous rhenium-GSH conjugate from a mixture of twenty amino acids has been demonstrated using fluorous solidphase extraction (FSPE). Additionally, the cytotoxicity of complexes 1 and 3 toward HeLa cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular uptake properties of complex 3 have been investigated by laser-scanning confocal microscopy.