Design and synthesis of lipid-mimetic cationic iridium complexes and their liposomal formulation for in vitro and in vivo application in luminescent bioimaging

Two iridium [Ir(NC)(2)(NN)](+) complexes with the diimine NN ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: NN - 2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, NC - methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (lambda(em) = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.Peer reviewe

Luminescent heterometallic gold-copper alkynyl complexes stabilized by tridentate phosphine

The reactions between trinuclear gold complex tppmAu 3Cl 3 (tppm = tris(diphenylphosphino)methane), arylacetylenes HC 2C 6H 4X and Cu + under basic conditions result in formation of the heterometallic complexes [tppm(AuC 2C 6H 4X) 3Cu] +, X = H (1), COOMe (2), CN (3), OMe (4), NH 2 (5). These compounds belong to one structural motif and consist of the heterometallic {(AuC 2C 6H 4X) 3Cu} core stabilized by the tridentate phosphine. Compounds 1-5 were characterized by polynuclear NMR and IR spectroscopy, ESI-MS and single-crystal X-ray analysis. Luminescence properties of these complexes have been studied and revealed a substantial red shift of the emission maxima with the increase in the electron donicity of the alkynyl ligands substituents in the 550-680 nm range. The theoretical calculations of the electronic structures showed that variations of the substituents on the alkynyl ligands display very little effect on the molecular structural parameters but show appreciable influence on the orbital energies and luminescence characteristics of the compounds under study. © 2012 The Royal Society of Chemistry.The authors greatly appreciate the financial support of Saint- Petersburg State University research grant 12.37.132.2011, the University of Eastern Finland (Russian–Finnish collaborative project), the Russian Foundation for Basic Research grants 11- 03-00974, 11-03-00541, and 11-03-92010.Peer Reviewe

Rhenium(I) Block Copolymers Based on Polyvinylpyrrolidone: A Successful Strategy to Water-Solubility and Biocompatibility

A series of diphosphine Re(I) complexes Re1–Re4 have been designed via decoration of the archetypal core {Re(CO)2(N^N)} through the installations of the phosphines P0 and P1 bearing the terminal double bond, where N^N = 2,2′-bipyridine (N^N1), 4,4′-di-tert-butyl-2,2′-bipyridine (N^N2) or 2,9-dimethyl-1,10-phenanthroline (N^N3) and P0 = diphenylvinylphosphine, and P1 = 4-(diphenylphosphino)styrene. These complexes were copolymerized with the corresponding N-vinylpyrrolidone-based Macro-RAFT agents of different polymer chain lengths to give water-soluble copolymers of low-molecular p(VP-l-Re) and high-molecular p(VP-h-Re) block-copolymers containing rhenium complexes. Compounds Re1–Re4, as well as the copolymers p(VP-l-Re) and p(VP-h-Re), demonstrate phosphorescence from a 3MLCT excited state typical for this type of chromophores. The copolymers p(VP-l-Re#) and p(VP-h-Re#) display weak sensitivity to molecular oxygen in aqueous and buffered media, which becomes almost negligible in the model physiological media. In cell experiments with CHO-K1 cell line, p(VP-l-Re2) and p(VP-h-Re2) displayed significantly reduced toxicity compared to the initial Re2 complex and internalized into cells presumably by endocytic pathways, being eventually accumulated in endosomes. The sensitivity of the copolymers to oxygen examined in CHO-K1 cells via phosphorescence lifetime imaging microscopy (PLIM) proved to be inessential

Synthesis and Intramolecular Azo Coupling of 4‑Diazopyrrole-2-carboxylates: Selective Approach to Benzo and Hetero [<i>c</i>]‑Fused 6<i>H</i>‑Pyrrolo[3,4‑<i>c</i>]pyridazine-5-carboxylates

A high yield synthesis of fluorescent benzo, thieno, and furo [<i>c</i>]-fused methyl 7-aryl-6<i>H</i>-pyrrolo­[3,4-<i>c</i>]­pyridazine-5-carboxylates, including unprecedented heterocyclic skeletons, was performed by the transformation of methyl 4-aminopyrrole-2-carboxylate into the corresponding diazo compound, followed by intramolecular azo coupling under acid conditions onto a nucleophilic aryl or hetaryl group in the 3-position. Azo coupling is completely regioselective and, according to DFT calculations, a kinetically controlled reaction. <i>N</i>-Methylation of 1,3-disubstituted 2<i>H</i>-pyrrolo­[3,4-<i>c</i>]­cinnolines occurs selectively at N5 under kinetic control, leading exclusively to 5-methyl-5<i>H</i>-pyrrolo­[3,4-<i>c</i>]­cinnoline derivatives

Polymeric Nanoparticles with Embedded Eu(III) Complexes as Molecular Probes for Temperature Sensing

Three novel luminescent Eu(III) complexes, Eu1&ndash;Eu3, have been synthesized and characterized with CHN analysis, mass-spectrometry and 1H NMR spectroscopy. The complexes display strong emission in dichloromethane solution upon excitation at 405 and 800 nm with a quantum yield from 18.3 to 31.6%, excited-state lifetimes in the range of 243&ndash;1016 ms at 20 &deg;C, and lifetime temperature sensitivity of 0.9%/K (Eu1), 1.9%/K (Eu2), and 1.7%/K (Eu3). The chromophores were embedded into biocompatible latex nanoparticles (NPs_Eu1&ndash;NPs_Eu3) that prevented emission quenching and kept the photophysical characteristics of emitters unchanged with the highest temperature sensitivity of 1.3%/K (NPs_Eu2). For this probe cytotoxicity, internalization dynamics and localization in CHO-K1 cells were studied together with lifetime vs. temperature calibration in aqueous solution, phosphate buffer, and in a mixture of growth media and fetal bovine serum. The obtained data were then averaged to give the calibration curve, which was further used for temperature estimation in biological samples. The probe was stable in physiological media and displayed good reproducibility in cycling experiments between 20 and 40 &deg;C. PLIM experiments with thermostated CHO-K1 cells incubated with NPs_Eu2 indicated that the probe could be used for temperature estimation in cells including the assessment of temperature variations upon chemical shock (sample treatment with mitochondrial uncoupling reagent)

Polynuclear cage-like Au(i) phosphane complexes based on a S2− template: observation of multiple luminescence in coordinated polyaromatic systems

A rational approach to the synthesis of cage-like compounds has been realized to build a new family of sulfido-phosphane Au(i) polynuclear complexes. Ditopic phosphane ligands with an extended aromatic system were used to obtain cage compounds with a clearly determined geometry. Au(i) complexes have been fully characterised in solution using spectroscopy methods, and DFT optimisation of the molecular structure gives additional arguments in favour of the suggested structural patterns. All complexes obtained are luminescent in solution and in the solid state, and display multiple emissions with an unusual combination of two phosphorescence bands and one fluorescence band. DFT calculations show that multiple emissions were mainly determined by IL and metal perturbed IL transitions. The ratio of singlet and triplet emission components depends on the distance between the ligand chromophoric centre and Au(i).This research has been supported by grants of the Russian Foundation for Basic Research 16-33-60109, 14-03-00970 and the Russian Presidential scholarship SP-2534.2016.1. The financial support from the Academy of Finland (grant 268993, I. O. K.) is acknowledged. The work was carried out using equipment of the Analytical Centre for Nano- and Biotechnologies (Peter the Great St Petersburg Polytechnic University with financial support from the Ministry of Education and Science of Russian Federation); and Centres for Magnetic Resonance, for Optical and Laser Materials Research, for Chemical Analysis and Materials Research, and Computer Centre (Research park of St Petersburg State University).Peer Reviewe

Toward Luminescence Vapochromism of Tetranuclear Au^I–Cu^I Clusters

A family of triphosphine gold–copper clusters bearing aliphatic and hydroxyaliphatic alkynyl ligands of general formula [HC­(PPh₂)₃Au₃Cu­(C₂R)₃]⁺ (R = cyclohexyl (<b>1</b>), cyclopentyl (<b>2</b>), Bu^t (<b>3</b>), cyclohexanolyl (<b>4</b>), cyclopentanolyl (<b>5</b>), 2,6-dimethylheptanolyl (<b>6</b>), 2-methylbutanolyl (<b>7</b>), diphenylmethanolyl (<b>8</b>)) was synthesized via a self-assembly protocol, which involves treatment of the (AuC₂R)_<i>n</i> acetylides with the (PPh₂)₃CH ligand in the presence of Cu⁺ ions and NEt₃. Addition of Cl^– or Br^– anions to complex <b>8</b> results in coordination of the halides to the copper atoms to give neutral HC­(PPh₂)₃Au₃CuHal­(C₂COHPh₂)₃ derivatives (Hal = Cl (<b>9</b>), Br (<b>10</b>)). The title compounds were characterized by NMR and ESI-MS spectroscopy, and the structures of <b>1</b>, <b>4</b>, <b>7</b>, and <b>8</b> were determined by single-crystal X-ray diffraction analysis. The photophysical behavior of all of the complexes has been studied to reveal moderate to weak phosphorescence in solution and intense emission in the solid state with a maximum quantum yield of 80%. Exposure of the solvent-free X-ray amorphous samples <b>8</b>–<b>10</b> (R = diphenylmethanolyl) to vapors of the polar solvents (methanol, THF, acetone) switches luminescence with a visible hypsochromic shift of emission of 50–70 nm. The vapochromism observed is tentatively ascribed to the formation of a structurally ordered phase upon absorption of organic molecules by the amorphous solids

Toward Luminescence Vapochromism of Tetranuclear Au^I–Cu^I Clusters

A family of triphosphine gold–copper clusters bearing aliphatic and hydroxyaliphatic alkynyl ligands of general formula [HC­(PPh₂)₃Au₃Cu­(C₂R)₃]⁺ (R = cyclohexyl (<b>1</b>), cyclopentyl (<b>2</b>), Bu^t (<b>3</b>), cyclohexanolyl (<b>4</b>), cyclopentanolyl (<b>5</b>), 2,6-dimethylheptanolyl (<b>6</b>), 2-methylbutanolyl (<b>7</b>), diphenylmethanolyl (<b>8</b>)) was synthesized via a self-assembly protocol, which involves treatment of the (AuC₂R)_<i>n</i> acetylides with the (PPh₂)₃CH ligand in the presence of Cu⁺ ions and NEt₃. Addition of Cl^– or Br^– anions to complex <b>8</b> results in coordination of the halides to the copper atoms to give neutral HC­(PPh₂)₃Au₃CuHal­(C₂COHPh₂)₃ derivatives (Hal = Cl (<b>9</b>), Br (<b>10</b>)). The title compounds were characterized by NMR and ESI-MS spectroscopy, and the structures of <b>1</b>, <b>4</b>, <b>7</b>, and <b>8</b> were determined by single-crystal X-ray diffraction analysis. The photophysical behavior of all of the complexes has been studied to reveal moderate to weak phosphorescence in solution and intense emission in the solid state with a maximum quantum yield of 80%. Exposure of the solvent-free X-ray amorphous samples <b>8</b>–<b>10</b> (R = diphenylmethanolyl) to vapors of the polar solvents (methanol, THF, acetone) switches luminescence with a visible hypsochromic shift of emission of 50–70 nm. The vapochromism observed is tentatively ascribed to the formation of a structurally ordered phase upon absorption of organic molecules by the amorphous solids

Coinage Metal Complexes Supported by the Tri- and Tetraphosphine Ligands

A series of tri- and tetranuclear phosphine complexes of d¹⁰ metal ions supported by the polydentate ligands, bis­(diphenylphosphinomethyl)­phenylphosphine (<i>PPP</i>) and tris­(diphenylphosphinomethyl)­phosphine (<i>PPPP</i>), were synthesized. All the compounds under study, [AuM₂(<i>PPP</i>)₂]³⁺ (M = Au (<b>1</b>), Cu (<b>2</b>), Ag (<b>3</b>)), [M₄(<i>PPPP</i>)₂]⁴⁺ (M = Ag (<b>4</b>), Au (<b>5</b>)), [AuAg₃(<i>PPPP</i>)₂]⁴⁺ (<b>6</b>), and [Au₂Cu₂(<i>PPPP</i>)₂(NCMe)₄]⁴⁺ (<b>7</b>), were characterized crystallographically. The trinuclear clusters <b>1</b>–<b>3</b> contain a linear metal core, while in the isostructural tetranuclear complexes <b>4</b>–<b>6</b> the metal framework has a plane star-shaped arrangement. Cluster <b>7</b> adopts a structural motif that involves a digold unit bridged by two arms of the <i>PPPP</i> phosphines and decorated two spatially separated Cu^I ions chelated by the remaining P donors. The NMR spectroscopic investigation in DMSO solution revealed the heterometallic clusters <b>2</b>, <b>3</b>, and <b>6</b> are stereochemically nonrigid and undergo reversible metal ions redistribution between several species, accompanied by their solvation–desolvation. The complexes <b>1</b>–<b>3</b> and <b>5</b>–<b>7</b> exhibit room temperature luminescence in the solid state (Φ_em = 6–64%) in the spectral region from 450 to 563 nm. The phosphorescence observed originates from the triplet excited states, determined by the metal cluster-centered d_σ* → p_σ transitions

Metalated Ir(III) Complexes Based on the Luminescent Diimine Ligands: Synthesis and Photophysical Study

A series of novel diimine (N^∧N) ligands containing developed aromatic [2,1-<i>a</i>]­pyrrolo­[3,2-<i>c</i>]­isoquinoline system have been prepared and used in the synthesis of Ir­(III) luminescent complexes. In organic solvents, the ligands display fluorescence which depends strongly on the nature of solvents to give moderate to strong orange emission in aprotic solvents and shows a considerable blue shift and substantial increase in emission intensity in methanol. Insertion of electron-withdrawing and -donating substituents into peripheral phenyl fragment has nearly no effect onto emission parameters. The ligands were successfully used to prepare the metalated [Ir­(N^∧C)₂(N^∧N)]⁺ complexes (where N^∧C = phenylpyridine (<b>N^∧C-1</b>), <i>p</i>-tolylpyridine (<b>N^∧C-2</b>), 2-(benzo­[<i>b</i>]­thiophen-2-yl)­pyridine (<b>N^∧C-3</b>), 2-benzo­[<i>b</i>]­thiophen-3-yl)­pyridine (<b>N^∧C-4</b>), and methyl 2-phenylquinoline-4-carboxylate (<b>N^∧C-5</b>)) using standard synthetic procedures. The complexes obtained display moderate to strong phosphorescence in organic solvents; the emission characteristics is determined by the nature of emissive triplet state, which varies substantially with the variations in the structure and donor properties of the C- and N-coordinating functions in metalating ligands. TD-DFT calculations show that for complexes <b>1</b>, <b>2</b>, and <b>4</b> the emission originates from the mixed ³MLCT/³LLCT excited states with the major contribution from the aromatic moiety of the diimine ligand, whereas in <b>3</b> the emissive triplet manifold is mainly located at the N^∧C ligand to give structured emission band typical for the ligand centered (LC) excited state. In the case of <b>5</b>, the phosphorescence may be also assigned to the mixed ³MLCT/³LLCT excited state; however, the major contribution is attributed to the aromatic moiety of the metalating N^∧C ligand