Functional Molecular Crystals from the Arylation of a Halogenoplatinum Complex: Stimuli Responsiveness, Comproportionation, and π-Bridged Dimerization.

A chloroplatinum complex was arylated to obtain stimuli-responsive molecular crystals. The resulting arylplatinum complex showed polymorph-dependent emission, mechano- and thermochromic luminescence as well as comproportionation and π-bridged dimerization. Simple mixing of structurally similar arylplatinum complexes at room temperature resulted in the transfer of their aryl groups (comproportionation), which allowed their mechanochromic profiles to be tuned. We also found that recrystallization of the complex afforded a dimerized product in which two platinum ions are bridged by aryl groups resulting in a very short (3.0466(10) Å) Pt-Pt distance.

Reversible Transition between Discrete and 1D Infinite Architectures: A Temperature-Responsive Cu(I) Complex with a Flexible Disilane-Bridged Bis(pyridine) Ligand.

A thermoresponsive structural change based on a disilane-bridged bis(pyridine) ligand and CuI is reported. Single-crystal X-ray analysis revealed that there are two polymorphs in the Cu(I) complex: octanuclear copper(I) complex at 20 °C and 1D staircase copper(I) polymer complex at -173 °C. The formation of these polymorphs is due to the flexibility of the ligand. Cu-I bond formation is observed upon cooling the sample from -10 °C to -170 °C. The temperature-induced phase transition progression was clarified by DSC, VT-PXRD, and VT-photoluminescence measurements and indicated a reversible temperature-controlled crystal-to-crystal phase transition. Observation on a VT-stage using a high-speed camera showed crystal cracking during single-crystal to single-crystal transitions between these polymorphic forms.

Postmortem genetic analysis of 17 sudden cardiac deaths identified nonsense and frameshift variants in two cases of arrhythmogenic cardiomyopathy.

Sudden death, or unexpected natural death of a healthy individual, is a serious problem in all nations. Sudden cardiac death (SCD) mainly due to ischemic heart diseases is the top cause of sudden death. However, there are pathophysiological conditions, referred to as sudden arrhythmic death syndrome, in which no apparent lesion can be identified even after complete conventional or ordinary autopsy. While postmortem genetic analyses have accumulated evidence about underlying genetic abnormality in such cases, the precise relationships between genetic background and the phenotype have been largely elusive. In this study, a retrospective investigation of 17 autopsy cases in which lethal arrhythmia was suspected to be the cause of death was carried out. Genetic analysis focusing on 72 genes reported to be associated with cardiac dysfunctions was performed, in combination with detailed histopathological and postmortem imaging examination, and a family study. As a result, in two cases of suspected arrhythmogenic cardiomyopathy (ACM), we found a nonsense variant in PKP2 and frameshift variant in TRPM4 gene. In contrast, the other 15 cases showed no morphological changes in the heart despite the presence of a frameshift variant and several missense variants, leaving the clinical significance of these variants obscure. The findings of the present study suggest that nonsense and frameshift variants could be involved in the morphological abnormality in cases of SCD due to ACM, while missense variants alone rarely contribute to massive structural changes in the heart.

Study of Polymer Nanofilms Using for High-Throughput Screening in the Development of Transdermal Therapeutic System.

We investigated polymer nanofilm (PNF) for use in high-throughput screening (HTS) to promote the development of transdermal therapeutic systems (TTS). The drug permeability of PNF with a 1 : 1 weight mix ratio of poly(L-lactic acid) (PLLA) and poly(methylhydrosiloxane) (PMHS) (PLLA/PMHS (1/1) PNF) and Strat-M® of the transdermal diffusion test membrane, was evaluated using 12 kinds of drugs with the logarithmic value of n-octanol/water partition coefficients of -4.70 to 3.86. The lag time of PLLA/PMHS (1/1) PNF made via polymer alloying was significantly shorter than that of Strat-M® for 10 drug types, and the formation of a highly diffusible PMHS-rich phase accompanying the formation of a sea-island structure was suggested as a contributing factor. Additionally, a high correlation was confirmed between the measured value for the logarithm of the apparent permeability coefficient of PLLA/PMHS (1/1) PNF and the literature values for the logarithm of the apparent permeability coefficient of human skin (r = 0.929). This study shows that PLLA/PMHS (1/1) PNF can reliably predict drug permeability in human skin and can potentially be used in HTS for developing TTS.

Synthesis of [1-13 C-5-12 C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate.

Isocitrate dehydrogenase 1 (IDH1) mutations that generate the oncometabolite 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG) have been identified in many types of tumors and are an important prognostic factor in gliomas. 2-HG production can be determined by hyperpolarized carbon-13 magnetic resonance spectroscopy (HP-13 C-MRS) using [1-13 C]-α-KG as a probe, but peak contamination from naturally occurring [5-13 C]-α-KG overlaps with the [1-13 C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1-13 C-5-12 C]-α-KG was synthesized. α-KG metabolism was measured via HP-13 C-MRS using [1-13 C-5-12 C]-α-KG as a probe. [1-13 C-5-12 C]-α-KG was synthesized in high yields, and successfully eliminated the signal from C5 of α-KG in the HP-13 C-MRS spectra. In HCT116 IDH1 R132H cells, [1-13 C-5-12 C]-α-KG allowed for unimpeded detection of [1-13 C]-2-HG. 12 C-enrichment represents a novel method to circumvent spectral overlap, and [1-13 C-5-12 C]-α-KG shows promise as a probe to study IDH1 mutant tumors and α-KG metabolism.

(9-Isocyanoanthracene)gold(I) Complexes Exhibiting Two Modes of Crystal Jumps by Different Structure Change Mechanisms.

The first examples of single crystals exhibiting salient effects by different structure change mechanisms are reported. The crystals of newly prepared aryl(9-isocyanoanthracene)gold(I) complexes jump in response to two different external stimuli: ultraviolet (UV) irradiation and cooling. The photosalient effect is triggered by photodimerization reaction of the anthracene moieties under photoirradiation. By contrast, the thermosalient effect is caused by anisotropic thermal contraction upon cooling without a chemical structure change. By taking advantage of the multiple-jump feature, we also show sequential jumps of crystals by cooling and then UV irradiation for demonstration of the programmed motion of molecular crystals.

Thermosalience in Macrocycle-Based Soft Crystals via Anisotropic Deformation of Disilanyl Architecture.

We describe here the preparation of soft crystals using disilanyl macrocycle C4 possessing four p-phenylenes circularly connected by four flexible disilane bonds. Single crystals of C4 exhibited a reversible thermal single-crystal-to-single-crystal (SCSC) phase transition behavior between two crystal phases accompanied by remarkable mechanical motion (thermosalient effect), as revealed by thermal analyses and X-ray diffraction measurements. Detailed structural analyses implied that flexibility of the parallelogram disilanyl architecture and molecular packing mode via weak intermolecular interactions facilitated a concerted structural transformation (parallel crank motion) of macrocycles in the crystal, thus resulting in the SCSC phase transition accompanied by anisotropic shrinking/elongation of the cells to induce the thermosalient effect. This work explores a new area of organosilicon chemistry and presents the potential utility of disilanyl macrocycles as soft crystals.

Aurophilicity-Mediated Construction of Emissive Porous Molecular Crystals as Versatile Hosts for Liquid and Solid Guests.

The first examples of porous molecular crystals that are assembled through Au⋅⋅⋅Au interactions of gold complex 1 are here reported along with their exchange properties with respect to their guest components. Single-crystal X-ray diffraction (XRD) analyses indicate that the crystal structure of 1/CH2 Cl2 ⋅pentane is based on cyclic hexamers of 1, which are formed through six Au⋅⋅⋅Au interactions. The packing of these cyclic hexamers affords a porous architecture, in which the one-dimensional channel segment contains CH2 Cl2 and pentane as guests. These guests can be exchanged through operationally simple methods under retention of the host framework of 1, which furnished 1/guest complexes with 26 different guests. A single-crystal XRD analysis of 1/eicosane, which contains the long linear alkane eicosane (n-C20 H42 ), successfully provided its accurately modeled structure within the porous material. These host-guest complexes show chromic luminescence with both blue- and redshifted emissions. Moreover, this porous organometallic material can exhibit luminescent mechanochromism through release of guests.

Synthesis and Tunable Optical Properties of C,N-Chelated Borate Luminophores Derived from Potassium Acyltrifluoroborates.

A new class of borate luminophores has been synthesized by a simple two-step reaction using potassium acyltrifluoroborates (KATs) as starting materials. The hydrazones obtained from reactions between KATs and 2-hydrazinopyridines followed by a cyclization resulted in the unprecedented formation of C,N-chelated six-membered bora-heterocycles. Under consideration of the results of DFT and TD-DFT calculations, four luminophores based on such bora-heterocycles are designed and synthesized, which exhibit a tunable fluorescence range from blue to red in the solid state. Moreover, one of the luminophores exhibits mechanofluorochromism from blue to yellow/green. As a result of the aforementioned mechanochromism of one of these luminophores, white-color emission was achieved by simply mixing the four luminophores.

Photoluminescent Ferroelastic Molecular Crystals.

Ferroelasticity has been reported for several types of molecular crystals, which show mechanical-stress-induced shape change under twinning and/or spontaneous formation of strain. Aiming to create materials that exhibit both ferroelasticity and light-emission characteristics, we discovered the first examples of ferroelastic luminescent organometallic crystals. Crystals of arylgold(I)(N-heterocyclic carbene)(NHC) complexes bend upon exposure to anisotropic mechanical stress. X-ray diffraction analyses and stress-strain measurements on these ferroelastic crystals confirmed typical ferroelastic behavior, mechanical twinning, and the spontaneous build-up of strain. A comparison with single-crystal structures of related gold-NHC complexes that do not show ferroelasticity shed light on the structural origins of the ferroelastic behavior.

Direct Dimesitylborylation of Benzofuran Derivatives by an Iridium-Catalyzed C-H Activation with Silyldimesitylborane.

Direct dimesitylborylation of benzofuran derivatives by a C-H activation catalyzed by an iridium(I)/N-heterocyclic carbene (NHC) complex in the presence of Ph2 MeSi-BMes2 afforded the corresponding dimesitylborylation products in good to high yield with excellent regioselectivity. This method provides a straightforward route to donor-(π-spacer)-acceptor systems with intriguing solvatochromic luminescence properties.

Near-IR Luminescent YbIII Coordination Polymers Composed of Pyrene Derivatives for Thermostable Oxygen Sensors.

Oxygen-sensitive and near-infrared (NIR) luminescent YbIII coordination polymers incorporating ligands based on pyrene derivatives were synthesized: YbIII -TBAPy and YbIII -TIAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoate)pyrene; TIAPy: 1,3,6,8-tetrakis(3,5-isophthalic acid)pyrene). The coordination structures of these materials have been characterized by means of electrospray ionization mass spectrometry, X-ray diffraction analysis, and thermogravimetric analysis. Moreover, the porous structure of YbIII -TIAPy has been evaluated by measuring its N2 adsorption isotherm. The NIR luminescence properties of YbIII -TBAPy and YbIII -TIAPy have been examined by acquiring emission spectra and determining emission lifetimes under air or argon and in vacuo. YbIII -TIAPy exhibited high thermal stability (with a decomposition temperature of 400 °C), intense luminescence (with an emission quantum yield under argon of 6.6 %), and effective oxygen-sensing characteristics. These results suggest that NIR luminescent YbIII coordination polymers prepared using pyrene derivatives could have applications in novel thermo-stable oxygen sensors.

Anisotropic Thermal Expansion as the Source of Macroscopic and Molecular Scale Motion in Phosphorescent Amphidynamic Crystals.

Herein we report a crystalline molecular rotor with rotationally modulated triplet emission that displays macroscopic dynamics in the form of crystal moving and/or jumping, also known as salient effects. Molecular rotor 2 with a central 1,4-diethynyl-2,3-difluorophenylene rotator linked to two gold(I) nodes, crystalizes as infinite 1D chains through intermolecular gold(I)-gold(I) interactions. The rotational motion changes the orientation of the central phenylene, changing the electronic communication between adjacent chromophores, and thus the emission intensities. Crystals of 2 showed the large and reversible thermal expansion/compression anisotropy, which accounts for 1) a nonlinear Arrhenius behavior in molecular-level rotational dynamics, which correlates with 2) changes in emission, and determines 3) the macroscopic crystal motion. A molecular rotor analogue 3 has properties similar to those of 2, suggesting a generalized way to control mechanical properties at molecular and macroscopic scales.

Mechanical-Stimulation-Triggered and Solvent-Vapor-Induced Reverse Single-Crystal-to-Single-Crystal Phase Transitions with Alterations of the Luminescence Color.

Luminescence alterations in solid-state materials upon external stimulations have attracted much attention due to their potential for the development of highly functional devices or sensors. We have previously reported the first examples of mechano-induced single-crystal-to-single-crystal (SCSC) phase transitions of gold(I) isocyanide complexes under concomitant emission-color changes. However, the reverse phase transitions of the crystals obtained after mechanical stimulation have not yet been achieved. Herein, a reversible change of the luminescence based on two SCSC phase transitions via mechanical cutting and solvent-vapor adsorption is described. Crystallization of a gold(I) complex that bears CF3 and biaryl moieties from CH2Cl2/MeOH afforded a green-emitting single crystal packed in a polar space group (Pna21). The green-emitting single crystals included MeOH molecules. Upon cutting the crystal under MeOH vapor at 22 °C, the green-emitting single crystal spontaneously changed into a centrosymmetric orange-emitting single crystal (P1̅) under concomitant release of MeOH. Remarkably, the initial green-emitting crystal could be recovered from the orange-emitting crystal by a solvent-induced SCSC transition under saturated MeOH vapor. The combination of two different types of SCSC phase transitions enables the reversible structural and photoluminescent alternations.

A Luminescent Dinuclear EuIII /TbIII Complex with LMCT Band as a Single-Molecular Thermosensor.

Temperature-dependent luminescence of a dinuclear EuIII /TbIII complex with a seven-coordinate structure is demonstrated. The dinuclear complex is composed of two lanthanide ions, six tetramethylheptanedionate ligands, and a bidentate phosphine oxide linker ligand. The dinuclear structure of the complex was characterized by single-crystal XRD. Intrinsic 4f-4f emission quantum yields of the dinuclear EuIII and TbIII complexes were 66 and 61 %, respectively. The luminescence color of the dinuclear EuIII /TbIII complex changed from red to green with increasing temperature. The thermosensing range based on the ratio of luminescence intensity (AEu /ATb ) was 100-450 K. The temperature-dependent luminescence is due to the presence of a ligand-to-metal charge-transfer state.

Synthesis and Evaluation of a 1,3a,6a-Triazapentalene (TAP)-Bonded System.

A method of synthesizing a directly connected 1,3a,6a-triazapentalene (TAP) ring system as a linearly bonded aromatic system with a planar form was established. Various TAP-dimers and a 2-alkyl-TAP-trimer were synthesized and their fluorescence properties were evaluated. Although the direct connection of the TAP ring with other TAP rings did not affect the fluorescence properties in diluted solvent, TAP-dimers showed unique fluorescence properties derived from the aggregation state under highly concentrated conditions. In particular, TAP-dimer 5 f showed aggregation-induced emission in highly concentrated solution, and 5 b showed typical mechanochromic fluorescence in the solid state despite their compact molecular size.

Structural Manipulation of Triboluminescent Lanthanide Coordination Polymers by Side-Group Alteration.

Novel Eu(III) coordination polymers with furan-based bridging ligands [Eu(hfa)3(Cy)] n and [Eu(hfa)3(Tol)] n (hfa: hexafluoroacetylacetonato, Cy: 2,5-bis(dicyclohexylphosphoryl)furan), Tol: 2,5-bis(di- p-tolylphosphoryl)furan) are reported. The rigidity of assembly steric structures was controlled by intermolecular interactions through the side groups in bridging ligands. They exhibited one of the best performances (thermal stability above 320 °C and external photoluminescence quantum yields of up to 71%) among reported lanthanide(III) compounds. The triboluminescence activity was demonstrated to be dependent on the mechanical stability of the coordination polymers, which was proportional to the number of hydrogen atoms in the side groups. The second example of a large TL/PL spectral difference in [Tb,Eu(hfa)3(Tol)] n also revealed discrete photophysical processes under the conditions of grinding and UV irradiation.

Sugar-Responsive Layer-by-Layer Film Composed of Phenylboronic Acid-Appended Insulin and Poly(vinyl alcohol).

Previous studies have shown that reversible chemical bond formation between phenylboronic acid (PBA) and 1,3-diol can be utilized as the driving force for the preparation of layer-by-layer (LbL) films. The LbL films composed of a PBA-appended polymer and poly(vinyl alcohol) (PVA) disintegrated in the presence of sugar. This type of LbL films has been recognized as a promising approach for sugar-responsive drug release systems, but an issue preventing the practical application of LbL films is combining them with insulin. In this report, we have proposed a solution for this issue by using PBA-appended insulin as a component of the LbL film. We prepared two kinds of PBA-appended insulin derivatives and confirmed that they retained their hypoglycemic activity. The LbL films composed of PBA-appended insulin and PVA were successfully prepared through reversible chemical bond formation between the boronic acid moiety and the 1,3-diol of PVA. The LbL film disintegrated upon treatment with sugars. Based on the results presented herein, we discuss the suitability of the PBA moiety with respect to hypoglycemic activity, binding ability, and selectivity for D-glucose.

Mechano-Responsive Luminescence via Crystal-to-Crystal Phase Transitions between Chiral and Non-Chiral Space Groups.

Herein, a novel mechano-responsive luminescent (MRL) material based on crystal-to-crystal phase transitions between crystals of a chiral and those of a centrosymmetric space group, accompanied by a change of emission properties, is described. Initially, a gold complex containing a biphenyl moiety, which exhibits an achiral structure in solution, afforded an orange-emitting amorphous phase together with a viscous isotropic oil after evaporation of the solvent. Upon pricking, the orange-emitting oil spontaneously crystallized either in a centrosymmetric or in a chiral space group while simultaneously changing the emission properties. Remarkably, grinding the chiral crystals induced a solid-state phase transition to the achiral crystals under concomitant changes of the emission properties.

Phosphorescence Control Mediated by Molecular Rotation and Aurophilic Interactions in Amphidynamic Crystals of 1,4-Bis[tri-(p-fluorophenyl)phosphane-gold(I)-ethynyl]benzene.

Here we present a structural design aimed at the control of phosphorescence emission as the result of changes in molecular rotation in a crystalline material. The proposed strategy includes the use of aurophilic interactions, both as a crystal engineering tool and as a sensitive emission probe, and the use of a dumbbell-shaped architecture intended to create a low packing density region that permits the rotation of a central phenylene. Molecular rotor 1, with a central 1,4-diethynylphenylene rotator linked to two gold(I) triphenylphosphane complexes, was prepared and its structure confirmed by single-crystal X-ray diffraction, which revealed chains mediated by dimeric aurophilic interactions. We showed that green-emitting crystals exhibit reversible luminescent color changes between 298 and 193 K, which correlate with changes in rotational motion determined by variable-temperature solid-state 2H NMR spin-echo experiments. Fast two-fold rotation with a frequency of ca. 4.00 MHz (τ = 0.25 µs) at 298 K becomes essentially static below 193 K as emission steadily changes from green to yellow in this temperature interval. A correlation between phosphorescence lifetimes and rotational frequencies is interpreted in terms of conformational changes arising from rotation of the central phenylene, which causes a change in electronic communication between the gold-linked rotors, as suggested by DFT studies. These results and control experiments with analogue 2, possessing a hindered tetramethylphenylene that is unable to rotate in the crystal, suggest that the molecular rotation can be a useful tool for controlling luminescence in the crystalline state.