Cyclometalated Platinum(II) Complexes in a Cis-N,N Configuration: Photophysical Properties and Isomerization to Trans Isomers.

Synthesis, isomerization, and photophysical properties of novel cis-N,N-cyclometalated complexes [Pt(C∧N)(l-Phe)] (C∧N = benzoquinolinate (1), phenylpyridinate (2), 2-(p-tolyl)pyridinate (3), and 1-phenylpyrazolate (4); l-Phe- = l-phenylalaninate) are reported herein. In solution, the cis forms of the complexes isomerize to their trans forms via an associative mechanism. This cis/trans isomerism barely influences the absorption and luminescence properties of the complexes in solution, except for a characteristic absorption at approximately 340 nm in the absorption spectra of the cis complexes that is not observed for the trans complexes. Interestingly, the cis complexes are spontaneously assembled in a crystalline phase and show bathochromic absorption and emission colors compared with those of the corresponding trans isomers, which are aggregated in an amorphous phase. cis-1 and cis-2 demonstrate hypsochromic luminescence mechanochromism. The influence of the geometrical isomerism on the photophysical properties and the isomerization mechanism are supported by density functional theory calculations.

o-Azophenylboronic Acid-Based Colorimetric Sensors for d-Fructose: o-Azophenylboronic Acids with Inserted Protic Solvent Are the Key Species for a Large Color Change.

Many boronic acid-based chemosensors for saccharides have been developed; however, their detection mechanisms have seldom been studied. In this study, we synthesized 10 o-azophenylboronic acid derivatives (azoBs) and conducted a fundamental study on the reactivity and the sensing mechanism of azoBs, which undergoes a large color change, e.g., from red to yellow, upon a reaction with saccharides. Their pH-independent formation constants were determined by spectrophotometric titration and then converted to the conditional formation constant K' at pH 7.4. A linear free energy relationship was established between log K' and the pKa of azoB. 11B NMR measurements indicate that in aprotic solvents, azoB forms a trigonal planar structure, while in protic solvents, it forms a quasi-tetrahedral structure (azoB-ROH) with a protic solvent molecule (ROH) inserted between the boronic acid moiety and the azo group. In addition, UV-vis spectroscopic studies showed that the color change during the reaction between azoB and d-fructose in ROH was caused by the release of the ROH from azoB-ROH by d-fructose. Based on the findings in this study, we proposed a guideline for designing an azoB-based chemosensor that exhibits high reactivity toward saccharides and a sufficient color change to allow for the visual detection of saccharides.

Luminescence of mononuclear Pt(ii) complexes with glycolate: external stimuli-induced excimer emission changes to oligomer emissions.

The emission properties and external stimuli-induced emission changes of novel mononuclear platinum(ii) complexes [PtII(4R2bpy)(gl)] (R = H (1), Me (2), tBu (3); 4R2bpy: 4,4'-disubstituted-2,2'-bipyridine; Hgl-: glycolate) were investigated. In solution, all complexes showed orange (λem: 617-623 nm) and green (λem: 488-495 nm) emissions at room temperature and 77 K, respectively, and the emission change is caused by a rigid chromic effect. X-ray crystallography of a red-emitting yellow trihydrate crystal of 1 (1R; λem: 663 nm) and an orange-emitting yellow anhydrate crystal of 3 (3O; λem: 560 nm) revealed the presence of weak π-π interactions between 4R2bpy moieties. When 1R was cooled to 153 K, the emission gradually turned to yellow (λem: 550 nm) owing to the restriction of inter-complex contacts after excitation. Exposing 1R to MeOH vapor rendered yellow-emitting yellow anhydrate crystals (1Y; λem: 558 nm), with the color remaining almost unchanged. Heating 1R gave orange-emitting orange anhydrate crystals (1O; λem: 597 nm). Consequently, the dehydration processes turn an excimer emission of 1R into two types of oligomer emissions (1Y and 1O). A green-emitting yellow 3.5 hydrate crystalline powder of 2 (2G; λem: 531 nm) was reversibly converted to an orange-emitting orange anhydrate powder (2O; λem: 564 nm) upon heating and exposure to H2O vapor, and the behavior is derived from switching between the monomer and an oligomer states. The crystal 3O exhibited an oligomer emission without responsiveness to external stimuli.

A water-soluble cyclometalated iridium(iii) complex for pH sensing based on aggregation-induced enhanced phosphorescence.

The novel water-soluble monoanionic Ir(iii) complex Na[Ir(ppy)2(SB-COO)] (2; Hppy = phenylpyridine; HSB-COOH = 4-carboxylanilinesalicylaldehyde Schiff base), which was obtained by the reaction of the novel Ir(iii) complex [Ir(ppy)2(SB-COOH)] (1) with NaOEt, in its aqueous solution, showed hydrogen ion (H+)-responsive aggregation-induced enhanced phosphorescence (AIEP). Both these complexes exhibited very weak and relatively strong emissions in solution and solid states, respectively. The pH-responsiveness of 2 was evaluated from its emission spectra in aqueous solution in the pH range of 8.7-1.8. Above pH 6, 2 showed weak emission with a maximum at 508 nm. Upon decreasing the pH to 4.7, AIEP with a bathochromic shift to 618 nm was induced by the aggregation of 1, whereby the intensity at 618 nm was increased approximately by 50-fold compared to that at pH 6.0. This enhancement is due to restrictions of the geometrical changes in the six-membered chelate ring of the ancillary ligand (Ir-N-C-C-C-O-) and of the intramolecular rotations in the excited state. The enhanced luminescence originates from spin-forbidden metal-to-ligand-ligand charge transfer (3MLLCT). Below pH 2.8, the emission intensity decreased owing to the decrease in the population of the emissive complex 1 upon dissociation of the ancillary ligand from the Ir(ppy)2 unit.

Chromism of Tartrate-Bridged Clamshell-like Platinum(II) Complex: Intramolecular Pt-Pt Interaction-Induced Luminescence Vapochromism and Intermolecular Interactions-Triggered Thermochromism.

A novel luminescent clamshell-like platinum(II) complex with rac-tartrate, rac-[{PtII(4Me2bpy)}2(µ-tart)] (Pt2; 4Me2bpy: 4,4'-dimethyl-2,2'-bipyridine; tartH22-: tartrate), was synthesized, and its vapo-, thermo-, and solvatochromic behavior was studied. The complex was isolated in four crystal forms, namely, Pt2·4H2O (color under ambient light: yellow, λem = 573 nm, intramolecular Pt···Pt separation: 3.55 Å), Pt2·4MeOH (red, 650 nm, 3.33 Å), anhydrate Pt2 (red, no luminescence, 3.70 Å), and Pt2·2H2O (orange, 595 nm, 3.60 Å). Vapo- and heat-responsive crystal-to-crystal phase transitions were observed by time- and/or temperature-dependent powder X-ray diffraction, and the molecular and crystal structures of the above crystal forms were determined by either single-crystal X-ray crystallography or Rietveld refinement of powder X-ray diffraction. Vapor diffusion of MeOH to Pt2·4H2O induced a reversible phase transition to Pt2·4MeOH. This structural transformation significantly changed the intramolecular Pt-Pt interactions, affecting the absorption and emission colors. Accordingly, the luminescence chromism originates from alternation of the luminescent nature between a triplet metal-ligand-to-ligand charge-transfer state (3(MLtart)LbpyCT) of Pt2·4H2O and a triplet metal-metal-to-ligand charge-transfer state (3MMLbpyCT) of Pt2·4MeOH. Heating Pt2·4H2O induced a phase transition to anhydrate Pt2, and under atmospheric conditions, anhydrate Pt2 transformed spontaneously to Pt2·2H2O. Vapor diffusion of H2O to Pt2·2H2O caused reconstruction of Pt2·4H2O. The thermochromism originates from changes in the intermolecular interactions between stacked complexes. The solvatochromism was evaluated using the Kamlet-Taft solvatochromic equation, the acceptor number, and the ET(30) scale for the solvent, and the hydrogen-bond acidity of the solvent contributed significantly to the solvent-dependent absorption properties.

Syn and anti conformers of di-ammonium aqua-bis(malonato)oxidovanadate(IV) in an anhydrate crystal.

The asymmetric unit of the title anhydrate compound, (NH4)2[VO(C3H2O4)2(H2O)], consists of two independent complex anions and four ammonium cations. In the complex anions, the VIV atoms are each coordinated by two malonate ligands, one water mol-ecule and one oxide O atom in a distorted octa-hedral geometry. The equatorial plane is formed by the malonate O atoms, while the axial positions are occupied by water and oxide O atoms. The difference between the two independent complexes is the relative conformation of the malonate ligands. The two ligands in one complex anion are in a syn conformation, while in the other they adopt an anti conformation. In the crystal, the complex anions inter-act with the counter-cations and adjacent anions through O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. Stacks of alternating layers consisting of either anti or syn isomers, formed with the aid of the hydrogen bonding, are observed. DFT calculations for the anti and syn isomers show a similar thermodynamic stability to each other. The crystal used for this analysis was an inversion twin with the ratio of the twin components being 0.270 (13):0.730 (13).

Change in Luminescence Induced by Solution-Mediated Phase-Transition of Cyclometalated Platinum(II) Complex with Isoquinoline Carboxylate.

Changes in luminescence due to solution-mediated phase transition (SMPT) and crystal-to-crystal phase transitions of a novel cyclometalated platinum(II) complex with isoquinoline-1-carboxylate (Iq-1-COO-) [Pt(bzq)(Iq-1-COO)] (bzq-: benzoquinolinate) were studied experimentally and theoretically. Recrystallization of the complex allowed three crystal forms depending on the solvent: red polymorph RDMF (λemi = 689 nm), yellow polymorph YDMSO (λemi = 641 nm), and red pseudopolymorph RBCHCl3 (λemi = 721 nm). Crystals of RDMF in the DMF solution at room temperature showed SMPT to yellow crystals YDMF (λemi = 627 nm), in which RDMF first dissolved partly into the solution, and then the dissolved complex crystallized as YDMF. RBCHCl3 exhibited crystal-to-crystal phase transitions to RDMF and YDMF by being heated to 150 °C and stored in atmospheric conditions, respectively. Molecular structures of each of the four crystal forms, analyzed by X-ray crystallography, showed different planarities because of the dihedral angles between the bzq- and Iq planes being 3.15, 4.80, 8.35, and 17.7° for RBCHCl3, RDMF, YDMSO, and YDMF, respectively. The planar complexes in RDMF and RBCHCl3 constructed dimers through intermolecular Pt-Pt and π-π interactions, whereas the distorted complexes in YDMF and YDMSO remained as monomers. Density functional theory (DFT) calculations, which reveal the relation between the molecular structure and thermodynamic stability, suggest that the SMPT is triggered by thermodynamic transformation from the metastable planar structure to the stable distorted structure. The intradimer interactions in RDMF and RBCHCl3 induced red-shifts in the absorption and emission colors from those of YDMF and YDMSO; thus, the photophysical properties of RBCHCl3 and RDMF originate from the MMLIqCT state in contrast with the MLIqCT/LbzqLIqCT character for YDMF and YDMSO. DFT and time-dependent DFT (TD-DFT) calculations in the ground and excited states provide insight into the structural, electronic, and optical properties.

Luminescence of tartrate bridged dinuclear 2,2'-bipyridine platinum(ii) complexes: emission color controlled by intra- and inter-molecular interactions in the solid state.

Novel dinuclear PtII complexes with a chiral (l-) and an achiral (meso-) tartrate [{PtII(bpy)}2(µ-x-tart)] (bpy: 2,2'-bipyridine; tartH22-: tartrate; x = l (1), meso (2)) and with a racemic (dl-) tartrate [{PtII(bpy)}2(µ-d-tart)][{PtII(bpy)}2(µ-l-tart)] (3) were synthesized, and the influence of their stereochemistry on their molecular and crystal structures affecting their luminescence was discussed. Effects of the dinuclearity on the structures and luminescence were revealed by comparison with those of a novel racemic mononuclear complex [PtII(bpy)(d-tartH2)][PtII(bpy)(l-tartH2)] (4). The X-ray crystallography showed the crystallization of 1 in two polymorphs, namely monoclinic 3[1·6H2O] (1α) and triclinic 2[1·6H2O] (1ß), and those of other complexes in monoclinic hydrate crystals 2·12.5H2O, 3·4H2O, and 4·H2O. The chiral complexes in 1α, 1ß, and 3·4H2O showed clamshell-like structures with Pt-Pt and π-π interactions, while the achiral complex in 2·12.5H2O displayed a twisted form without intramolecular interactions. The complexes in 1α were assembled in a right-handed helical arrangement through significant Pt-Pt interactions, and those in 1ß and 3·4H2O were stacked in one-dimensional columns through significant and slight π-π interactions, respectively. The complex in 2·12.5H2O constructed an intermolecular dimer through Pt-Pt interactions with its adjacent complex. The crystal structure of 4·H2O displayed a three-dimensional network architecture through π-π interactions and hydrogen bonding. These crystals exhibited luminescence depending on their molecular and crystal structures (λmax nm = 535 (4·H2O), 569 (3·4H2O), 621 (2·12.5H2O), 649 (1ß), and 656 (1α)). The formations of intermolecular dimers and clamshell-like structures through Pt-Pt interactions in 2·12.5H2O and in 3·4H2O, respectively, lead to red-shifts in emissions compared to 4·H2O, and further low-energy emissions of 1α and 1ß were derived from the intermolecular Pt-Pt and π-π interactions, respectively.

Mechanochromism in the luminescence of novel cyclometalated platinum(II) complexes with α-aminocarboxylates.

Six novel phosphorescent cyclometalated platinum(ii) complexes with α-aminocarboxylato ligands, [Pt(II)(ppy)L] (ppy = 2-phenylpyridinato, L(-) = Gly, Ala, Leu, Ile, Phe, Sar), were synthesized, and the structures were determined by X-ray crystallography. [Pt(II)(ppy)L] (L(-) = Gly, Ala) in crystals are in monomeric structures and stack through π-π interactions to form columns, and the features of the luminescence are similar to each other and those in solution, suggesting little influence of the π-π interactions on the luminescence. [Pt(II)(ppy)Leu] has a dimeric structure through the Pt-Pt interaction. [Pt(II)(ppy)Sar] showed two pseudo-polymorphs, one of which contains both monomeric and dimeric forms, while the other consists of only dimeric units. Intra-dimer π-π interactions were observed in both the dimeric units. [Pt(II)(ppy)L] (L(-) = Leu, Ile, Phe) in the solid state displayed different spectral patterns of luminescence from those in solution, suggesting that the dimeric structures through the Pt-Pt interaction in the solid state are dissociated into the corresponding monomeric ones in solution. The complexes except [Pt(II)(ppy)Phe] in the solid state exhibited reversible luminescent mechanochromism in response to the mechanical grinding and treatment with a few drops of solvent. These phenomena are induced by the change in the energy level of the triplet state due to the change in the extent of intermolecular interactions, which appeared due to the crystalline-amorphous phase conversion.

Crystal structure of 4,4'-dimeth-oxy-2,2'-bi-pyridine.

In the title compound, C12H12N2O2, the dihedral angle between the planes of the two pyridine rings is 5.8 (1)°. Neighbouring mol-ecules are linked via C(Me)-H⋯N inter-actions, generating a two-dimensional sheet structure; C-H⋯π inter-actions further link the mol-ecules into a three-dimensional network. An overlapped arrangement of parallel pyridine rings in neighbouring mol-ecules [centroid-to-centroid distance = 3.6655 (15) Å] is observed in the crystal structure.

Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer.

BACKGROUND: We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study. METHODS: Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m(2) we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response. RESULTS: In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35-4.63). CONCLUSIONS: In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

Dinuclear nickel(II) complexes with 2,5-diamino-1,4-benzoquinonediimine ligands as precatalysts for the polymerization of styrene: electronic and steric substituent effects.

Catalytic polymerization of styrene with a series of dinuclear nickel(II) complexes [{Ni(acac)}2{µ-C6H2-(N-Ph-R)4}] (R = 4-Et (1a), 4-OEt (1b), 2-OEt (1c), 2-Et (1d), and 2,6-Et2 (1e)) in the presence of methylaluminoxane was studied under various conditions to evaluate the substituent effect. The activity of 1a-1e, except 1c, increased with an increase in the reaction temperature, and the highest activity (7.46 × 10(5) g PS mol(-1) Ni h(-1)) was obtained using 1e at 70 °C. The electronic and steric properties of the ligand influenced the activity at room temperature, 50 °C, and 60 °C, steric factors barely, whereas electronic factors slightly dominated the activity at 70 °C. The activity with 1c remained constant at all temperatures, probably due to the masking of the active center by the formation of inactive N,N',O-chelate species. The obtained polymers were atactic polystyrenes with molecular weights and molecular weight distributions in the range of 15,000-43,400 and 1.71-2.14, respectively. While a clear dependence of the molecular weight and molecular weight distribution on the temperature was observed, no significant dependence on the substituent was noted.

An ortho-rhom-bic polymorph of N (1),N (4)-diphenyl-3,6-bis-(phenyl-imino)-cyclo-hexa-1,4-diene-1,4-di-amine.

A new ortho-rhom-bic polymorph of the title compound, C30H24N4, with a density of 1.315 Mg m(-3), has been obtained. The mol-ecule is centrosymmetric with the centroid of the cyclo-hexa-1,4-diene ring located on an inversion center. The two unique benzene rings are almost perpendicular to each other [dihedral angle = 86.70 (6)°] and are oriented at dihedral angles of 30.79 (5) and 68.07 (5)° with respect to the central cyclo-hexa-diene ring. In the crystal, π-π stacking is observed between the central cyclo-hexa-1,4-diene-1,4-di-amine unit and a phenyl ring of a neighboring mol-ecule [centroid-centroid distance = 3.7043 (7) Å]. The crystal structure of the triclinic polymorph [Ohno et al. (2014 ▶). Acta Cryst. E70, o303-o304] showed chains running along the b-axis direction through weak C-H⋯π inter-actions.

N (1),N (4)-Diphenyl-3,6-bis-(phenyl-imino)-cyclo-hexa-1,4-diene-1,4-di-amine.

In the title compound, C30H24N4, the central benzo-quinonedi-imine moiety is approximately planar, with a maximum deviation of 0.044 (14) Å. The four terminal phenyl rings are twisted by 44.95 (11), 54.90 (10), 44.98 (10) and 50.68 (11)° with respect to the mean plane the benzo-quinonedi-imine unit. In the crystal, mol-ecules are linked by weak C-H⋯π inter-actions into supra-molecular chains running along the b-axis direction.

Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

PURPOSE: The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. RESULTS: Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese patients. CONCLUSIONS: The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.

Construction of an M3L2A6 cage with small windows from a flexible tripodal ligand and Cu(hfac)3.

An M3L2A6 cage has been prepared with small windows from a tripodal ligand, L, and Cu(hfac)2. Cold spray ionization mass spectrometry of a mixture of L and Cu(hfac)2 revealed the formation of a Cu3L2hfac6 cage in solution. X-ray crystallography showed that the Cu3L2hfac6 cage included neutral molecules such as THF and CHCl3. Furthermore, the six hfac anions have been shown to play an important role in holding neutral guest molecules securely in place.

2-{[2,2-Bis(diethyl-amino)-ethan-2-ylium-thio-yl]sulfan-yl}-1,1-bis-(diethyl-amino)-ethyl-ium bis-(perchlorate).

The title salt, C(20)H(42)N(4)S(2) (2+)·2ClO(4) (-), was obtained from the reaction of bis-(diethyl-amino)-carbeniumdithio-carboxyl-ate, (Et(2)N)(2)C(2)S(2), with Fe(ClO(4))(2)·6H(2)O in CH(2)Cl(2). The title compound, in which one of the S atoms of (Et(2)N)(2)C(2)S(2) is bound to a 1,1-bis-(diethyl-amino)-ethane moiety, has two carbenium C atoms, and the charge compensation is provided by two perchlorate anions. The N(2)C-CS(2) bond length is 1.512 (4) Å, corresponding to a C-C single bond, and the dihedral angle between N(2)C- and -CS(2) planes [72.0 (2)°] is smaller than that of (Et(2)N)(2)C(2)S(2) [82.0 (1)°]. The crystal structure features C-H⋯S hydrogen bonds.