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We report herein new luminescent rhenium(I) perfluorobiphenyl complexes that reacted specifically with the cysteine residue of the π-clamp sequence (FCPF) to afford novel peptide-based imaging reagents, photosensitisers for singlet oxygen and enzyme sensors.

In this article, we report the design, synthesis, and characterization of a series of cyclometalated iridium(III) polypyridine complexes containing a perfluorobiphenyl (PFBP) moiety [Ir(N^C) 2 (bpy-PFBP)](PF 6 ) (bpy-PFBP = 4-( S -(perfluoro-(1,1'-biphenyl)-4-yl)- N -mercaptoethylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = 2-phenylpyridine (Hppy) ( 1a ), 2-(4-hydroxymethylphenyl)pyridine (Hppy-CH 2 OH) ( 2a ), 2-((1,1'-biphenyl)-4-yl)pyridine (Hpppy) ( 3a ), 2-((4'-hydroxymethyl-1,1'-biphenyl)-4-yl)pyridine (Hpppy-CH 2 OH) ( 4a ), 2-phenylquinoline (Hpq) ( 5a ), 2-(4-hydroxymethylphenyl)quinoline (Hpq-CH 2 OH) ( 6a )). Their PFBP-free counterparts [Ir(N^C) 2 (bpy-C4)](PF 6 ) (bpy-C4 = 4-( N - n -butylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = Hppy ( 1b ), Hppy-CH 2 OH ( 2b ), Hpppy ( 3b ), Hpppy-CH 2 OH ( 4b ), Hpq ( 5b ), Hpq-CH 2 OH ( 6b )) were also prepared for comparison studies. Upon irradiation, all the complexes displayed intense and long-lived greenish-yellow to orange luminescence in solutions under ambient conditions and in low-temperature alcohol glass. Reactions of the PFBP complexes with peptides containing the FCPF sequence via the π-clamp-mediated cysteine conjugation afforded luminescent peptide conjugates that exhibited rich photophysical properties. Using complex 3a as an example, we demonstrated that the conjugation of complexes to organelle-targeting peptides is an effective means to modulate their intracellular localization behavior, which was further shown to be important to their performance in photodynamic therapy. The results of this work will contribute to the development of photofunctional transition metal complexes as theranostic agents.

This communication reports novel luminescent rhenium(I)-polypyridine complexes appended with a perylene diimide (PDI) or benzoperylene monoimide (BPMI) moiety through a non-conjugated linker. The photophysical and photochemical properties originating from the interactions of the metal polypyridine and perylene units were exploited to afford new cellular reagents with thiol-sensing capability and excellent photocytotoxic activity., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the synthesis and characterization of three cyclometalated iridium(III) polypyridine complexes containing a 2,4-dinitrophenyl ether moiety [Ir(pq) 2 (N^N)](PF 6 ) (Hpq=2-phenylquinoline; N^N=4-(N-(4-(2,4-dinitrophenoxy)benzyloxy)carbonyl)aminomethyl-4'-methyl-2,2'-bipyridine (bpy-dinitro-1) (1a), 4-(2,4-dinitrophenoxy)methyl-4'-methyl-2,2'-bipyridine (bpy-dinitro-2) (2a), 4-(4-(2,4-dinitrophenoxy)phenyl)-2,2'-bipyridine (bpy-dinitro-3) (3a)) as intracellular sensors for biothiols. Due to the quenching effect of the dinitroaromatic moiety, these complexes were extremely weakly emissive. Upon the reaction with biothiols, however, the emission was turned on as a consequence of the departure of the quenching unit. The results from a range of experiments demonstrated that complex 1a was noncytotoxic under the conditions used for confocal imaging, showed facile cellular uptake, and can serve as a phosphorogenic intracellular sensor for biothiols including glutathione (GSH) and hydrogen sulfide., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We present a new class of phosphorescent cyclometalated iridium(III) bipyridyl-phenylenediamine complexes [Ir(N^C)2 (bpy-DA)](PF6 ) (bpy-DA=4-(N-(2-amino-5-methoxyphenyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C=2-(2,4-difluorophenyl)pyridine (Hdfppy) (1 a), 2-phenylpyridine (Hppy) (2 a), 2-phenylquinoline (Hpq) (3 a), 2-phenylcinchoninic acid methyl ester (Hpqe) (4 a)) and their triazole counterparts [Ir(N^C)2 (bpy-T)](PF6 ) (bpy-T=4-((6-methoxybenzotriazol-1-yl)methyl)-4'-methyl-2,2'-bipyridine; HN^C=Hdfppy (1 b), Hppy (2 b), Hpq (3 b), Hpqe (4 b)). Upon photoexcitation, the diamine complexes exhibited fairly weak green to red phosphorescence under ambient conditions whereas the triazole derivatives emitted strongly. The photophysical properties of complexes 2 a and 2 b have been studied in more detail. Upon protonation, the diamine complex 2 a displayed increased emission intensity, but the emission properties of its triazole counterpart complex 2 b were independent on the pH value of the solution. Also, complex 2 a was found to be readily converted into complex 2 b upon reaction with NO under aerated conditions, resulting in substantial emission enhancement of the solution. The reaction was highly specific toward NO over other reactive oxygen and nitrogen species (RONS) as revealed by spectroscopic analyses. The lipophilicity and cellular uptake efficiency of the diamine complexes have been examined and correlated to their molecular structures. Also, cell-based assays showed that these complexes were noncytotoxic toward human cervix epithelioid carcinoma (HeLa) cells (at 10 μM, 4 h, percentage survival ≈80-95%). Additionally, the diamine complexes have been used to visualize intracellular NO generated both exogenously in HeLa cells and endogenously in RAW 264.7 murine macrophages by laser-scanning confocal microscopy., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of phosphorescent cyclometalated iridium(III) polypyridine complexes appended with a β-D-glucose moiety [Ir(N^C)2(bpy-TEG-ONCH3-β-D-glc)](PF6) [bpy-TEG-ONCH3-β-D-glc = 4-(10-N-methyl-N-(β-D-glucopyranosyl)-amino-oxy-2,5,8-trioxa-dec-1-yl)-4'-methyl-2,2'-bipyridine; HN^C = 2-((1,1'-biphenyl)-4-yl)benzothiazole) (Hbt) (1a), 2-phenylpyridine (Hppy) (2a), 2-phenylquinoline (Hpq) (3a), 7,8-benzoquinoline (Hbzq) (4a)] has been synthesized and characterized. The D-galactose counterparts [Ir(N^C)2(bpy-TEG-ONCH3-β-D-gal)](PF6) [bpy-TEG-ONCH3-β-D-gal = 4-(10-N-methyl-N-(β-D-galactopyranosyl)-amino-oxy-2,5,8-trioxa-dec-1-yl)-4'-methyl-2,2'-bipyridine; HN^C = Hbt (1b), Hppy (2b), Hpq (3b), Hbzq (4b)] and a sugar-free bt complex [Ir(bt)2(bpy-TEG-OMe)](PF6) [bpy-TEG-OMe = 4-(2,5,8,11-tetraoxa-dodec-1-yl)-4'-methyl-2,2'-bipyridine] (1c) have also been prepared. Upon photoexcitation, all the complexes displayed intense and long-lived triplet metal-to-ligand charge-transfer ((3)MLCT) [dπ(Ir) → π*(N^N)] or triplet intraligand ((3)IL) (π → π*) (N^C and N^N) emission. The lipophilicity, the cellular uptake efficiency, and cytotoxicity of the complexes toward human cervix epithelioid carcinoma cells (HeLa) have been examined. Temperature dependence and chemical inhibition experiments indicated that the transport of bt-glucose complex 1a across the cell membrane occurred through an energy-requiring process such as endocytosis, in additional to a pathway that was mediated by glucose transporters (GLUTs). Importantly, the cellular uptake efficiency of this complex was found to be strongly dependent on hormonal stimulation and inhibition, rendering it a new phosphorescent metabolic indicator. Additionally, laser-scanning confocal microscopy revealed that the complex was localized in the mitochondria and highly resistant to photobleaching compared to a fluorescent organic glucose derivative 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-d-glucose (2-NBDG).

We report the synthesis, photophysical behavior, and biological properties of new cyclometalated iridium(iii) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety; these complexes have been utilized as the first phosphorescent bioorthogonal probes for azide-modified biomolecules.

We report here a new class of biological reagents derived from luminescent rhenium(I) polypyridine complexes modified with a poly(ethylene glycol) (PEG) pendant. The PEG-amine complexes [Re(N(^)N)(CO)(3)(py-PEG-NH(2))](PF(6)) (py-PEG-NH(2) = 3-amino-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine, MW(PEG) = 5000 Da, PDI(PEG) < 1.08; N(^)N = 1,10-phenanthroline (phen) (1-PEG-NH(2)), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)-phen) (2-PEG-NH(2)), 4,7-diphenyl-1,10-phenanthroline (Ph(2)-phen) (3-PEG-NH(2))) and [Re(bpy-PEG)(CO)(3)(py-NH(2))](PF(6)) (bpy-PEG = 4-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine; py-NH(2) = 3-aminopyridine) (4-PEG-NH(2)) have been synthesized and characterized. The photophysical properties, lipophilicity, water solubility, cytotoxic activity, and cellular uptake properties of these complexes have been compared to those of their PEG-free counterparts [Re(N(^)N)(CO)(3)(py-Et-NH(2))](PF(6)) (py-Et-NH(2) = 3-amino-5-(N-(ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-Et-NH(2)), Me(4)-phen (2-Et-NH(2)), Ph(2)-phen (3-Et-NH(2))) and [Re(bpy-Et)(CO)(3)(py-NH(2))](PF(6)) (bpy-Et = 4-(N-(ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine) (4-Et-NH(2)). The PEG complexes exhibited significantly higher water solubility and lower cytotoxicity (IC(50) = 6.6 to 1152 μM) than their PEG-free counterparts (IC(50) = 3.6 to 159 μM), indicating that the covalent attachment of a PEG pendant to rhenium(I) polypyridine complexes is an effective way to increase their biocompatibility. The amine complexes 1-PEG-NH(2)-4-PEG-NH(2) have been activated with thiophosgene to yield the isothiocyanate complexes [Re(N(^)N)(CO)(3)(py-PEG-NCS)](PF(6)) (py-PEG-NCS = 3-isothiocyanato-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-NCS), Me(4)-phen (2-PEG-NCS), Ph(2)-phen (3-PEG-NCS)), and [Re(bpy-PEG)(CO)(3)(py-NCS)](PF(6)) (py-NCS = 3-isothiocyanatopyridine) (4-PEG-NCS) as a new class of luminescent PEGylation reagents. To examine their PEGylation properties, these isothiocyanate complexes have been reacted with a model substrate n-butylamine, resulting in the formation of the thiourea complexes [Re(N(^)N)(CO)(3)(py-PEG-Bu)](PF(6)) (py-PEG-Bu = 3-n-butylthioureidyl-5-(N-(2-(ω-methoxypoly(1-oxapropyl))ethyl)aminocarbonyl)pyridine; N(^)N = phen (1-PEG-Bu), Me(4)-phen (2-PEG-Bu), Ph(2)-phen (3-PEG-Bu)), and [Re(bpy-PEG)(CO)(3)(py-Bu)](PF(6)) (py-Bu = 3-n-butylthioureidylpyridine) (4-PEG-Bu). Additionally, bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with the isothiocyanate complexes to yield bioconjugates 1-PEG-BSA-4-PEG-BSA and 1-PEG-PEI-4-PEG-PEI, respectively. Upon irradiation, all the PEGylated BSA and PEI conjugates exhibited intense and long-lived emission in aqueous buffer under ambient conditions. The DNA-binding and polyplex-formation properties of conjugate 3-PEG-PEI have been studied and compared with those of unmodified PEI. Furthermore, the in vivo toxicity of complex 3-PEG-NH(2) and its PEG-free counterpart 3-Et-NH(2) has been investigated using zebrafish embryos as an animal model. Embryos treated with the PEG complex at high concentrations revealed delayed hatching, which has been ascribed to hypoxia as a result of adhering of the complex to the external surface of the chorion.

A new class of luminescent cyclometalated iridium(III) polypyridine fluorous complexes has been designed; the fluorous pendant not only plays an important role in the photophysical and biological properties of the complexes, but also allows the facile isolation of biomolecules labeled with these complexes with fluorous solid-phase extraction (FSPE)., (This journal is © The Royal Society of Chemistry 2011)

Four new luminescent cyclometallated iridium(III) bis(quinolylbenzaldehyde) diimine complexes [Ir(qba)(2)(N⁁N)](PF(6)) (Hqba = 4-(2-quinolyl)benzaldehyde, N⁁N = 2,2'-bipyridine, bpy (1); 1,10-phenanthroline, phen (2); 3,4,7,8-tetramethyl-1,10-phenanthroline, Me(4)-phen (3); 4,7-diphenyl-1,10-phenanthroline, Ph(2)-phen (4)) have been synthesised and characterised, and their electronic absorption, emission and electrochemical properties investigated. The X-ray crystal structures of complexes 1 and 2 have been determined. Upon irradiation, complexes 1-4 exhibited intense and long-lived orange-yellow emission in fluid solutions at 298 K and in alcohol glass at 77 K. The emission has been assigned to a triplet intra-ligand ((3)IL) excited state associated with the qba ligand, probably with mixing of some triplet metal-to-ligand charge-transfer ((3)MLCT) (dπ(Ir) →π*(qba)) character. Reductive amination reactions of complexes 1-4 with the protein bovine serum albumin (BSA) afforded the bioconjugates 1-BSA-4-BSA, respectively. Upon photoexcitation, these bioconjugates displayed intense and long-lived (3)MLCT (dπ(Ir) →π*(N⁁C)) emission in aqueous buffer at 298 K. The cross-linked nature of the Ir-BSA bioconjugates has been verified by SDS-PAGE. Additionally, the cytotoxicity of the complexes towards human cervix epithelioid carcinoma (HeLa) cells has been examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assays, and the cellular uptake of complex 4 has been investigated by laser-scanning confocal microscopy and flow cytometry.