Mechanical and Thermal ON-OFF Switching of the Vapochromic Behavior of a Luminescent Polymorphic Pt(II) Complex.

Vapochromic materials that exhibit color/luminescence changes induced by vapor exposure have attracted considerable attention. Herein, we report the grinding- and heating-induced ON-OFF switching of the vapochromic behavior of [Pt(ppyCl2)(Clacac)] (1; ppyCl2 = 2-(3-chlorophenyl)-4-chloropyridinato, Clacac = 3-chloroacetylacetonato). 1 formed yellow and orange polymorphs (1-Y and 1-O), and 1-Y could be converted to 1-Og, which showed a very similar crystal structure but with a broadened X-ray diffraction pattern compared with that of 1-O. Moreover, 1-Og can be reversibly transformed into 1-O via heating and grinding. Notably, 1-Og underwent a N,N-dimethylacetamide vapor-induced transformation to 1-Y, whereas 1-O did not undergo such a transformation. These results indicate the ON-OFF switching of vapochromic behavior induced via grinding and heating. This finding will be beneficial for developing intelligent molecular devices.

Efficacy and Safety of Vibegron Add-on Therapy in Men With Persistent Storage Symptoms After Receiving Alpha 1-Blocker or Phosphodiesterase 5 Inhibitor: A Preliminary Study.

OBJECTIVE: To investigate the efficacy and safety of vibegron add-on therapy in men with persistent storage symptoms receiving α-1 blockers or PDE5 inhibitor for benign prostatic hyperplasia and then determine the independent factors affecting the efficacy of vibegron. METHODS: Vibegron 50 mg was administered for 12 weeks to 42 patients (72.0 ± 8.2 years) with persistent storage symptoms who had taken α-1 blockers (22 patients) or PDE5 inhibitor (20 patients). The primary endpoint was change in the overactive Bladder (OAB) Symptom Score from baseline to end of treatment. The secondary endpoints were changes in each question of several questionnaires, maximum flow rate and residual urine volume. Finally, independent factors affecting the efficacy of vibegron were investigated. RESULTS: Total OAB Symptom Score was significantly decreased (6.21 ± 3.12 vs 4.38 ± 2.46; P < .001). Although each score of several questionnaires, especially for storage symptoms, improved significantly, no significant improvement was found in stress incontinence, straining, bladder pain and urethral pain in the Core Lower Urinary Tract Symptom score. Maximum flow rate and residual urine volume did not change, and no patient discontinued vibegron because of adverse events. Multiple regression analysis showed that OAB Symptom Score, Core Lower Urinary Tract Symptom score, prostate volume and monotherapy with α-1 blocker were independent factors affecting the efficacy of vibegron. CONCLUSION: Add-on therapy of vibegron to monotherapy with α-1 blockers or PDE5 inhibitor for patients with benign prostatic hyperplasia and persistent storage symptoms was effective and safe.

Coordination-based vapochromic behavior of a luminescent Pt(ii) complex with potassium ions.

Vapochromic Pt(ii) complexes that exhibit color and luminescence changes induced by the presence of vapor molecules have drawn considerable attention because of their potential use as vapor sensors. Generally, the vapochromic responsiveness of Pt(ii)-based complexes is difficult to envisage, because a typical molecular design facilitates the stabilization of a vapor-adsorbed form through weak intermolecular interactions. Herein, we investigate the vapochromic behavior of a Pt(ii) complex with potassium ions, which act as vapor coordination sites, by strongly stabilizing the vapor-adsorbed form. Upon exposure to N,N-dimethylacetamide and N,N-dimethylformamide vapors, the complex exhibits crystal structural transformation with luminescence spectral changes. Crystal structural analysis indicates that the vapor molecules are coordinated to the potassium ions after vapor exposure. This study suggests the possibility of inducing Pt(ii)-based vapochromic responsiveness through establishing potassium-ion-based vapor coordination sites.

Liquid-liquid interface-promoted formation of a porous molecular crystal based on a luminescent platinum(II) complex.

Porous molecular crystals (PMCs) should function as new-generation functional porous materials, but the selective crystallisation of PMCs is still difficult. Herein we demonstrate that the liquid-liquid interface between the MeOH/H2O mixture and alkanes promotes the crystallisation of a Pt(ii)-based PMC, rather than the nonporous form. This new crystallisation method allows control of not only the porosity but also the luminescence of the Pt(ii) complex crystal.

Bright Luminescent Platinum(II)-Biaryl Emitters Synthesized Without Air-Sensitive Reagents.

Transition-metal complexes bearing biaryl-2,2'-diyl ligands tend to show intense luminescence. However, difficulties in synthesis have prevented their further functionalization and practical applications. Herein, a series of platinum(II) complexes bearing biaryl-2,2'-diyl ligands, which have never been prepared in air, were synthesized through transmetalation and successive cyclometalation of biarylboronic acids. This approach does not require any air- or moisture-sensitive reagents and features a simple synthesis even in air. The resulting (Et4 N)2 [Pt(m,n-F2 bph)(CN)2 ] (m,n-F2 bph=m,n-difluorobiphenyl-2,2'-diyl) complexes exhibit intense green emissions with high quantum efficiencies of up to 0.80 at 298 K. The emission spectral fitting and variable-temperature emission lifetime measurements indicate that the high quantum efficiency was achieved because of the tight packing structure and strong σ-donating ability of bph.

Tadalafil is sufficiently effective for severe chronic prostatitis/chronic pelvic pain syndrome in patients with benign prostatic hyperplasia.

OBJECTIVES: To investigate the efficacy of tadalafil for patients with benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome. METHODS: Tadalafil 5 mg was given each morning for 12 weeks to patients diagnosed as having either moderate or severe lower urinary tract symptoms. Voiding symptoms were compared between patients with a high (≥4; high group) and low (<4; low group) pain subscore of the National Institutes of Health Chronic Prostatitis Symptom Index before and after tadalafil administration. The correlation between changes in the Chronic Prostatitis Symptom Index and the International Prostate Symptom Score during treatment was also investigated. RESULTS: At baseline, the pain subscore of the Chronic Prostatitis Symptom Index was high (≥4) in 24 of 74 (32.4%) patients. The International Prostate Symptom Score in the group with a high pain subscore was significantly higher than that in the group with a low pain subscore. International Prostate Symptom Score, National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscore were all significantly improved after treatment. The change in the Chronic Prostatitis Symptom Index total score correlated positively with the change in the International Prostate Symptom Score. The decrease in the International Prostate Symptom Score was significantly greater in the group with high versus low pain subscore. CONCLUSIONS: Tadalafil is sufficiently effective in the treatment of patients with benign prostatic hyperplasia and severe chronic prostatitis/chronic pelvic pain syndrome.

Stability Tuning of Vapor-Adsorbed State of Vapochromic Pt(II) Complex by Introduction of Chiral Moiety.

New luminescent Pt(II) complexes with chiral ester chains, [PtCl2( R, R-bpybe)] (R-1; bpybe = 2,2'-bipyridine-4,4'-dicarboxylic acid dibutyl ester) and its racemic mixture (rac-1) with the chiral isomer, S-1, were synthesized, and their vapochromic behavior was investigated. Single-crystal X-ray structural analysis revealed that the rac-1 crystal was composed of only one crystallographically independent column formed by alternating stacking of R-1 and S-1 by the effective intermolecular Pt···Pt interaction. In contrast, three types of columnar structures with different Pt···Pt interactions were found for the R-1 crystal, probably because of the different packing of the chiral ester chains between the columns. Consequently, the estimated molecular volume of R-1 was slightly larger than that in the racemic crystal rac-1, although they have the same chemical formula. The X-ray structure of the toluene-adsorbed rac-1 (rac-1·toluene) also indicated that the intermolecular Pt···Pt interaction, which was effective for unsolvated rac-1, was completely canceled out by adsorption of toluene vapor. Both the rac-1 and R-1 crystals exhibited similar vapochromism driven by toluene vapor adsorption/desorption that switched the emission origin between the strongly emissive 3MMLCT (metal-metal-to-ligand charge transfer) to the weakly emissive 3π-π* phosphorescence. Although both crystals had the same chemical formula, the toluene vapor desorption temperature of R-1·toluene (84 °C) was obviously lower than that of rac-1·toluene (107 °C), suggesting that the binding interaction with toluene molecules was weaker in R-1·toluene than in rac-1·toluene.

Quantitative Solvent-Free Thermal Synthesis of Luminescent Cu(I) Coordination Polymers.

The luminescent Cu(I) coordination polymers [Cu2I2( m, m'-bpy)] n (CuI- m; m, m'-bpy = m, m'-bipyridine; m = 3, 4) were successfully synthesized by the solvent-free thermal reaction of the metal salt CuI with the organic linkers m, m'-bpy. Powder X-ray diffraction analysis revealed that CuI-3 was immediately formed when a mixture of CuI and 3,3'-bpy was ground in a mortar at room temperature (20 °C). In contrast, a temperature >120 °C was required to synthesize the CuI-4 isomer, probably because of the higher melting point of the 4,4'-bpy linker. Although excess bpy linker was necessary to afford the CuI- m in high yield, the quantitative synthesis, without any purification processes, was successfully achieved by simple heating at 140 °C, whereby the excess bpy linker was thermally removed by evaporation. Single crystal X-ray structural analysis indicated that in CuI-3 the dinuclear {Cu2I2} rhombic cores were bridged by 3,3'-bpy linkers. A similar structure was observed for CuI-4; however, the intermolecular π-π stacking that was effective in CuI-4 was suppressed in CuI-3 because of the twisted configuration of the two pyridyl rings of the 3,3'-bpy linker. CuI-3 exhibited bright green emission with the maximum (λem) at 519 nm and a high emission quantum yield (Φ = 0.58) in the solid state at room temperature, in contrast to the weak red emission of CuI-4 (λem = 653 nm, Φ < 0.01). Emission decay analysis and density functional theory calculations suggested that the CuI- m emissions could be attributed to the delayed fluorescence from the metal-to-ligand charge-transfer excited state effectively mixed with the halide-to-ligand charge-transfer excited state.

Two-way vapochromism of a luminescent platinum(ii) complex with phosphonic-acid-functionalized bipyridine ligand.

A luminescent Pt(ii) complex [Pt(CN)2(H4dpbpy)] (1P; H4dpbpy = 2,2'-bipyridine-4,4'-diphosphonic acid) bearing a phosphonic-acid-functionalized bipyridine ligand was successfully synthesized and its unique two-way vapochromic behaviour investigated. X-ray structure analyses of both the anhydrous 1P and penta-hydrated 1P·5H2O phases clearly reveal the activation of intermolecular PtPt interactions through the adsorption of water vapour. Emission spectroscopy reveals that the penta-hydrated 1P·5H2O complex exhibits an orange emission at 585 nm that shifts in two directions, to a blue-green emission at 469 nm by drying at 100 °C or to a red emission at 701 nm by drying under vacuum at room temperature. Thermogravimetric analyses and powder X-ray diffraction studies clearly reveal that anhydrous 1P, with negligible intermolecular PtPt interactions, is formed by drying at 100 °C whereas the monohydrate 1P·H2O phase, with effective PtPt interactions, is formed by drying under vacuum.

Methanol-Triggered Vapochromism Coupled with Solid-State Spin Switching in a Nickel(II)-Quinonoid Complex.

A highly methanol-selective vapochromic response has been realized in a NiII -quinonoid complex, [Ni(HLMe )2 ] (H2 LMe =4-methylamino-6-methyliminio-3-oxocyclohexa-1,4-dien-1-olate) which exhibits a reversible structural transformation including a coordination geometrical change between the square-planar and octahedral structure by the selective uptake of methanol vapor. This was accompanied by a remarkable color change between purple and orange, as well as temperature-robust spin-state switching in the solid state under ambient conditions. It is remarkable that the properties are derived by the fine structural modification of the quinonoid ligand such as methyl or ethyl analogues. Such a system has high potential for applications in memory devices as well as chemical sensors and smart responsive materials.

Proton-switchable vapochromic behaviour of a platinum(ii)-carboxy-terpyridine complex.

We synthesized a carboxy-substituted Pt(ii)-terpyridine complex, i.e. [PtCl(Hctpy)]Cl ([1H]Cl; Hctpy = 4'-carboxy-2,2':6',2''-terpyridine), that shows interesting switchable vapochromic behaviour upon protonation/deprotonation of the carboxy group. The as-synthesized dark-blue amorphous-like solid [1H]Cl·3H2O was converted to a yellow crystalline solid, [1H]Cl·H2O, upon exposure to various polar organic solvent vapours (e.g., acetonitrile, ethanol, 1-propanol, and dichloromethane), which promote the removal of water molecules. The reaction of [1H]Cl·3H2O with aqueous ammonia afforded a deprotonated bright-yellow crystalline complex, i.e. [PtCl(ctpy)]·H2O (1·H2O), which exhibits red luminescence with an emission maximum at 622 nm. Although the colour of 1·H2O was not affected by exposure to various polar organic solvent vapours, interesting vapochromic luminescence with a remarkable red-shift of the emission maximum from 622 to 652 nm was observed upon exposure to saturated water vapour to form orange crystalline 1·3.5H2O. X-ray structural analysis revealed that the planar and neutral complex molecule 1 forms a one-dimensional columnar structure with an intermolecular PtPt distance of 3.518(2) Å in the orange crystalline 1·3.5H2O, while the cationic molecule [1H]+ in the protonated form, [1H]Cl·H2O, generates a dimeric structure with an intermolecular PtPt distance of 3.439(2) Å. This difference suggests that the vapochromic behaviours of the protonated and deprotonated forms could be caused by structural changes induced by water-vapour adsorption/desorption, which affect the intermolecular PtPt distance, thereby changing the energy of the metal-metal-to-ligand charge-transfer (MMLCT) transition. These contrasting results for the protonated and deprotonated complexes clearly indicate that the hydrophilicity of complex 1 is significantly affected by protonation/deprotonation of the carboxy group. In addition, quasi-reversible conversion between [1H]Cl·3H2O and 1·H2O was achieved by exposure of the protonated and deprotonated forms to triethylamine and humid hydrochloric acid vapours, respectively.

Shape-Memory Platinum(II) Complexes: Intelligent Vapor-History Sensor with ON-OFF Switching Function.

A novel platinum(II)-diimine complex, [Pt(CN)2 (H2 dcphen)] (1; H2 dcphen=4,7-dicarboxy-1,10- phenanthroline), was synthesized and its vapochromic shape-memory behavior was evaluated. The as-synthesized amorphous purple solid, [Pt(CN)2 (H2 dcphen)]⋅2 H2 O (1 P), exhibited vapochromic behavior in the presence of alcoholic vapors through transformation to a red, crystalline, porous, vapor-adsorbed form, 1 R⊃vapor. The obtained 1 R⊃vapor complex released the adsorbed vapors upon heating without collapse of the porous structure. The vaporfree, porous 1 R⊃open could detect water or n-hexane vapor, although these vapors could not induce 1 P-to-1 R⊃vapor transformation, and 1 R⊃open could easily be converted to the initial 1 P by manual grinding. These results indicate that 1 is a new shape-memory material that functions through formation and collapse of the porous framework with an emission change upon vapor-adsorption and grinding; this enables it to exhibit vapor history and ON-OFF switching sensing functions.

Occult hepatitis B virus infection in Japanese chronic hemodialysis patients.

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti-HBc) was determined by various chemiluminescent immunoassays. HBV-DNA was quantified in patients positive for anti-HBc using quantitative real-time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg-positive and 218 (20.9%) were anti-HBc-positive. All HBsAg-positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg-negative and anti-HBc-positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.

A novel role of the C-terminus of b 0,+ AT in the ER-Golgi trafficking of the rBAT-b 0,+ AT heterodimeric amino acid transporter.

The heterodimeric complex composed of rBAT (related to b(0,+) amino acid transporter), a single-membrane-spanning glycosylated heavy chain, and b(0,+)AT, a putative 12-membrane-spanning non-glycosylated light chain, is an amino acid transporter that mediates the activity of system b(0,+), a major apical transport system for cystine and dibasic amino acids in renal proximal tubule and small intestine. The C-terminus of b(0,+)AT has been proposed to play an important role in the functional expression of the heterodimeric transporters. In the present study, to reveal the roles of the C-terminus, we analysed b(0,+)AT mutants whose C-termini were sequentially deleted or replaced by site-directed mutagenesis in polarized MDCKII (Madin-Darby canine kidney II), non-polarized HEK-293 (human embryonic kidney-293) and HeLa cells. Although the deletion of C-terminus of b(0,+)AT did not affect the formation of a heterodimer with rBAT, it resulted in the loss of apparent transport function, owing to the failure of the plasma-membrane targeting of rBAT-b(0,+)AT heterodimeric complex associated with incomplete glycosylation of rBAT. A motif-like sequence Val(480)-Pro(481)-Pro(482) was identified in the C-terminus of b(0,+)AT to be responsible for the C-terminus action in promoting the trafficking of rBAT-b(0,+)AT heterodimeric complex from the ER (endoplasmic reticulum) to Golgi apparatus. This is, to our knowledge, the first demonstration of the active contribution of the C-terminus of a light-chain subunit to the intracellular trafficking of heterodimeric transporters. Because the motif-like sequence Val(480)-Pro(481)-Pro(482) is well conserved among the C-termini of light-chain subunits, common regulatory mechanisms could be proposed among heterodimeric amino acid transporters.

Molecular identification of a renal urate anion exchanger that regulates blood urate levels.

Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.

Identification of a novel Na+-independent acidic amino acid transporter with structural similarity to the member of a heterodimeric amino acid transporter family associated with unknown heavy chains.

We identified a novel Na(+)-independent acidic amino acid transporter designated AGT1 (aspartate/glutamate transporter 1). AGT1 exhibits the highest sequence similarity (48% identity) to the Na(+)-independent small neutral amino acid transporter Asc (asc-type amino acid transporter)-2 a member of the heterodimeric amino acid transporter family presumed to be associated with unknown heavy chains (Chairoungdua, A., Kanai, Y., Matsuo, H., Inatomi, J., Kim, D. K., and Endou, H. (2001) J. Biol. Chem. 276, 49390-49399). The cysteine residue responsible for the disulfide bond formation between transporters (light chains) and heavy chain subunits of the heterodimeric amino acid transporter family is conserved for AGT1. Because AGT1 solely expressed or coexpressed with already known heavy chain 4F2hc (4F2 heavy chain) or rBAT (related to b(0,+)-amino acid transporter) did not induce functional activity, we generated fusion proteins in which AGT1 was connected with 4F2hc or rBAT. The fusion proteins were sorted to the plasma membrane and expressed the Na(+)-independent transport activity for acidic amino acids. Distinct from the Na(+)-independent cystine/glutamate transporter xCT structurally related to AGT1, AGT1 did not accept cystine, homocysteate, and l-alpha-aminoadipate and exhibited high affinity to aspartate as well as glutamate, suggesting that the negative charge recognition site in the side chain-binding site of AGT1 would be closer to the alpha-carbon binding site compared with that of xCT. The AGT1 message was predominantly expressed in kidney. In mouse kidney, AGT1 protein was present in the basolateral membrane of the proximal straight tubules and distal convoluted tubules. In the Western blot analysis, AGT1 was detected as a high molecular mass band in the nonreducing condition, whereas the band shifted to a 40-kDa band corresponding to the AGT1 monomer in the reducing condition, suggesting the association of AGT1 with other protein via a disulfide bond. The finding of AGT1 and Asc-2 has established a new subgroup of the heterodimeric amino acid transporter family whose members associate not with 4F2hc or rBAT but with other unknown heavy chains.