The impact of China's high-speed rail investment on regional economy and air pollution emissions.

The high-speed rail (HSR) network in China has experienced rapid development since the 2000s. In 2016, the State Council of the People's Republic of China issued a revised version of the "Mid- and Long-term Railway Network Plan", detailing the expansion of the railway network and construction of an HSR system. In the future, the HSR construction efforts in China will further increase, which is considered to impact regional development and air pollutant emissions. Therefore, in this paper, we apply a transportation network-multiregional computable general equilibrium (CGE) model to estimate the dynamic effects of HSR projects on economic growth, regional disparities, and air pollutant emissions in China. The results indicate that HSR system improvement could generate a positive economic impact but could also increase emissions. The gross domestic product (GDP) growth per unit investment cost stimulated by HSR investment is found to be the largest in eastern China but the smallest in the northwest regions. Conversely, HSR investment in Northwest China contributes to a substantial reduction in regional disparities in terms of the GDP per capita. In regard to air pollution emissions, HSR construction in South-Central China results in the largest increase in CO2 and NOX emissions, while for CO, SO2, and fine particulate matter (PM2.5) emissions, the largest increase occurs due to HSR construction in Northwest China. At the regional level, the provinces with large changes in accessibility also experience large changes in their air pollutant emissions.

Visible-light-induced C(sp3)-H thiocyanation of pyrazolin-5-ones: a practical synthesis of 4-thiocyanated 5-hydroxy-1H-pyrazoles.

A direct, aerobic and visible light photocatalytic approach to synthesize 4-thiocyanated 5-hydroxy-1H-pyrazoles via cross-coupling of pyrazolin-5-ones with ammonium thiocyanate is described. Under redox-neutral and metal-free conditions, a series of 4-thiocyanated 5-hydroxy-1H-pyrazoles could be easily and efficiently obtained in good to high yields by using low-toxicity and inexpensive ammonium thiocyanate as the thiocyanate source.

Consumption-driven freight turnover of interprovincial trade and related air pollution emissions in China from 2007 to 2012.

Freight transport has become increasingly important regarding CO2 and air pollutant emissions in China but has rarely been assessed using consumption-based methods. Based on the multi-regional input-output tables of China, in this work, we use structural path analysis (SPA) to link interprovincial trade-related freight turnover to responsible sectors of final consumption. We find that from 2007 to 2012, the interprovincial trade turnover in China increased by 39% and reached 3.87 × 1012 ton-km in 2012, associated with emissions of approximately 370 Mt CO2, 6.1 Mt CO and 2.5 Mt NOx. We also find that each 10 thousand CNY final consumption on interprovincial traded goods in China may drive 2000 ton-km of freight turnover and generate 200 kg CO2 emissions. This environmental burden will decrease by a factor of five if only locally produced goods are consumed. Final consumption in equipment, construction, service and food caused the most significant freight turnover; they drive a large quantity of low-value-added but heavy-weight semifinished products, such as mining and metal products, to be shipped across the provinces at the very upstream of the supply chain. Policymakers should aim to optimize China's industrial geographical layout and trade structure to facilitate deep CO2 reductions associated with the freight transport system.

Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.

Structural Insights into the Host-Guest Complexation between ß-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives.

Understanding the host-guest chemistry of α-/ß-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used ß-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, ß-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests.

Effects of mancozeb on citrus rhizosphere bacterial community.

Multiple and consecutive application of fungicide might damage the rhizosphere bacterial community of citrus. In order to evaluated effect of mancozeb on the chemical properties of citrus-cultivated soil and the richness and diversity of rhizosphere bacterial community. The abundance response of rhizosphere bacterial groups without application or with application of 1.333 g mg-1 mancozeb for 2, 4, 6 and 8 times were investigated, and further studied the relationship between the rhizosphere bacterial community and chemical properties of citrus-cultivated soil. We found the rhizosphere bacterial composition and diversity were distinct between soil planted with citrus and without citrus, in addition, the abundance of rhizosphere-associated bacterial species in the soil planted with citrus increased significantly. Meanwhile, the chemical properties and the richness and diversity of rhizosphere bacterial community of the soil planted with citrus did not significantly change among different application frequence of mancozeb. Moreover, with the increased applying times of mancozeb, the relative abundance of Candidatus, Saccharibacteria, Parcubacteria, and Proteobacteria increased but the abundance of Nitrospirae decreased. In our one-year trial, there were less adverse effects of mancozeb on the citrus-cultivated rhizosphere by the repeated application of mancozeb. Therefore, mancozeb, as a fungicide, could be used multiple times to control citrus disease.

Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

Investigation of Solubility Behavior of Canagliflozin Hydrate Crystals Combining Crystallographic and Hirshfeld Surface Calculations.

Canagliflozin (CG) was a highly effective, selective and reversible inhibitor of sodium-dependent glucose co-transporter 2 developed for the treatment of type 2 diabetes mellitus. The crystal structure of CG monohydrate (CG-H2O) was reported for the first time while CG hemihydrate (CG-Hemi) had been reported in our previous research. Solubility and dissolution rate results showed that the solubility of CG-Hemi was 1.4 times higher than that of CG-H2O in water and hydrochloric acid solution, and the dissolution rates of CG-Hemi were more than 3 folds than CG-H2O in both solutions. Hirshfeld surface analysis showed that CG-H2O had stronger intermolecular forces than CG-Hemi, and water molecules in CG-H2O participated three hydrogen bonds, forming hydrogen bond networks. These crystal structure features might make it more difficult for solvent molecules to dissolve CG-H2O than CG-Hemi. All these analyses might explain why the dissolution performance of CG-Hemi was better than CG-H2O. This work provided an approach to predict the dissolution performance of the drug based on its crystal structure.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

Dietary Effects on Biological Parameters and Gut Microbiota of Harmonia axyridis.

The multicolored Asian lady beetle (Harmonia axyridis, H. axyridis, Coleoptera, and Coccinellidae) is an effective biocontrol agent against agricultural pests. Previous studies have suggested that amount, type, and the quality of food can directly affect the biological aspects of H. axyridis. In this study, we investigated the influence of the food sources (Acyrthosiphon pisum Harris, Diaphorina citri Kuwayama, and artificial diets) on the gut microbiota diversity and the biology, reproductive variables, and population growth indicators of H. axyridis. Three kinds of diets were considered in this study: (1) HY: the adult of A. pisum Harris (HY group); (2) HM: the adult of D. citri Kuwayama (HM group); (3) HR: artificial diets prepared by blending a portion of fresh homogenized pork liver (15 g), honey (3 g), distilled water (35 ml) (HR group). We found that gut microbiota composition and diversity and the biological parameters differed when H. axyridis was fed with different diets. The abundance of Enterobacteriaceae was the highest in the HM group, followed by HY group, and was the lowest in the HR group. The abundance of Staphylococcaceae was highest in the HR group. Among the gut fungi, Davidiellaceae and Wallemiaceae were the highest and lowest in the HY group; Incertae_sedis were the major gut fungi in the HR group. Meanwhile, the changes of biological parameters may be correlated with the changes of Streptococcaceae abundance, Micrococcaceae abundance, Staphylococcaceae abundance, and Enterobacteriaceae abundance in responds to diet changes. To sum up, these data suggest that different diets can influence the changes in adult H. axyridis gut microbiota, consequently affecting the biological parameters.

On the Single-Crystal Structure of Tenofovir Alafenamide Mono-Fumarate: A Metastable Phase Featuring a Mixture of Co-Crystal and Salt.

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya® for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy® for the treatment of chronic hepatitis B. Vemlidy® is also a monotherapeutic regimen formulated as TAF hemifumarate (1; TAF:fumarate = 2:1). In this work, we report for the first time the single-crystal structure of TAF fumarate hemihydrate (2, TAF:fumarate:H2O = 2:2:1). Compound 2 is initially documented as a salt in which one proton of the fumaric acid migrates to the amine group of the adenine moiety in TAF. It was recently proposed that ca. 20-30% proton is transferred to the N atom on the aromatic adenine backbone. We herein provide definitive single-crystal X-ray diffraction results to confirm that 2, though phase pure, is formed as a mixture of co-crystal (75%) and salt (25%). It features two pairs of TAF fumarates, wherein one of the four H atoms on the fumaric acid is transferred to the N atom of the adjacent adenine moiety while the other three carboxylates remain in their intrinsic acid form. Compound 2 is a metastable phase during the preparation of 1 and can be isolated by halting the reaction during the refluxing of TAF and fumaric acid in acetonitrile (MeCN). Our report complements the previous characterizations of TAF monofumarate, and its elusive structural patterns are finally deciphered.

A versatile ultrafine and super-absorptive H+-modified montmorillonite: application for metabolic syndrome intervention and gastric mucosal protection.

Metabolic syndrome (MetS) includes central obesity, hypertension, insulin resistance, and dyslipidemia and is closely related to nonalcoholic fatty liver disease, atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus, involving multiple causative factors. Current drug therapies for intervention and amelioration of MetS are essential in clinical treatment of metabolic disease. In this report, we proposed an H+-modified montmorillonite (H-MMT) using an acid modification method with ultrafine structure and super absorption ability as a potential drug for MetS. Hamsters fed a high-fat diet were orally treated with H-MMT and simvastatin was applied as a control. H-MMT lowered lipids by decreasing intestinal absorption and promoting lipid excretion, subsequently preventing obesity, fatty liver, and hyperlipidemia. Moreover, H-MMT was significantly safer and better tolerated by the liver compared to simvastatin, which was hepatotoxic. In addition, we found that H-MMT had protective effects on gastric mucosal damage. Therefore, this versatile H-MMT provides a potential strategy to effectively improve MetS and provide gastric mucosal protection in clinical applications.

Enhanced antitumour effect for hepatocellular carcinoma in the advanced stage using a cyclodextrin-sorafenib-chaperoned inclusion complex.

Hepatocellular carcinoma (HCC) is a hypervascular tumour characterized by tumour-driven neovascularization. The degrees of blood oxygen saturation (DBOS), microvessel density (MVD) and tumour size (TS) are indicators in identifying the development stage of HCC. Herein, we proposed an HCC staging model using HepG2 tumour-bearing mice based on DBOS, MVD and TS. According to the patterns of these three criteria, HCC was classified into four stages: early, intermediate, advanced and end stages. The advanced stage was characterized by MVD of 50-90 (number per mm2), DBOS of 12-16% and TS of 250-600 mm3, which poses a critical challenge in HCC therapy. In order to efficiently control and treat HCC in the advanced stage, we developed a cyclodextrin (CD)-based chaperoned inclusion complex using Sorafenib (Sor), ß-CD and γ-CD (SCD) via the co-crystallization method. The structural study manifested that CDs could encapsulate Sor with the hydrophobic cavities at a 1 : 1 stoichiometry ratio. The crystallographic analysis indicated that Sor-ß-CD presented a diagonal stacking pattern, while Sor-γ-CD possessed a channel-type structure. The resultant chaperoned inclusion complexes significantly improved the solubility, dissolution rate and drug release of Sor, leading to superior pharmacokinetics, biodistribution and biosafety through oral administration. The antitumour effect was then evaluated on a mouse model with advanced HCC through oral administration and intratumour injection. The treatment involving the oral administration of SCDs showed a promising therapeutic effect on advanced HCC, which efficiently blocked angiogenesis and inhibited tumour progression. For the treatments using intratumour injections, only Sor-γ-CD exhibited a satisfactory anti-tumour effect with reduction in TS, MVD and DBOS. The enhanced therapeutic performance of Sor-γ-CD was attributed to its channel-type structure, which had an impact on the dissociation and release of the drug. Thus, Sor-γ-CD can be used as a potential pro-drug for clinical medicine and basic research to treat HCC.

Quantitation of polymorphic impurity in entecavir polymorphic mixtures using powder X-ray diffractometry and Raman spectroscopy.

Entecavir was used for the treatment of chronic hepatitis B through inhibiting hepatitis B virus. The anhydrous form of entecavir (ENT-A) often appeared as impurity polymorph in the manufacturing process of entecavir monohydrate (ENT-H) such as granulation, drying and compression. Since different crystal forms might affect drug bioavailability and therapeutic effect, it was vital to control the ENT-A content of the drug product. The work aimed to develop useful methods to assess ENT-A weight percentage in ENT-H. Powder X-ray diffractometry (PXRD) and Raman spectrometric methods were applied. Binary mixtures with different ratios of pure ENT-H and pure ENT-A were scanned using PXRD and Raman to obtain spectra. Then peak heights and peak areas versus weight percentage were used to construct calibration curves. The best linear regression analysis data for PXRD and Raman method were found to be R2 = 0.9923 and R2 = 0.9953, in the weight ratio range of 2.1-20.2% w/w% of ENT-A in binary mixtures. Limit of detection (LOD) of ENT-A was 0.38% and limit of quantitation (LOQ) was 1.15% for PXRD method. LOD and LOQ for Raman method were 0.48% and 1.16%. The results showed that PXRD and Raman methods: both were precise and accurate, and could be used for measurement of ENT-A content in the selected weight percentage range. Partial least squares (PLS) algorithm with four data pre-processing methods: including multiplicative scatter correlation (MSC), standard normal variate (SNV), first and second derivatives were applied and evaluated using prediction errors. The best performance of PLS was R2 = 0.9958 with RMSEC (0.44%) and RMSEP (0.65%). Multivariate analysis for Raman spectra showed similar good results with univariate analysis, and would be an advantageous method when there were overlapped peaks in the spectra. In summary, the proposed PXRD and Raman method could be developed for the quality control of ENT-H. And Raman was a more promising method in industrial practice due to its slightly better precision, accuracy and time-saving advantage.

Crystal structure of (S)-5-chloro-N-({2-oxo-3-[4-(3-oxomorpholin-4-yl)phen-yl]oxazolidin-5-yl}meth-yl)thio-phene-2-carboxamide.

The asymmetric unit of the crystal of the title compound (common name rivaroxaban), C19H18ClN3O5, contains two rivaroxaban mol-ecules with different conformations; the C-C-N-C torsion angles between the oxazolidine and thio-phene rings are -171.1 (7) and -106.8 (9)° in the two independent mol-ecules. In the crystal, classical N-H⋯O hydrogen bonds and weak C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular architecture.

Anhydrates and hemihydrate of tasimelteon: Synthesis, structure, and pharmacokinetic study.

Two new crystal forms of tasimelteon TSM-I and TSM-II were reported here. Crystallization of crude in methanol or mixture solvent results in anhydrate crystal form (TSM-I) and hemihydrate crystal form (TSM-II) respectively. To the best of our knowledge, it is the first report about crystalline form of tasimelteon. The two crystal forms were exhaustively characterized by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, Raman Spectra, Differential Scanning Calorimetry, Thermogravimetric Analysis, Solid State NMR Spectroscopy and Powder X-ray diffraction and Single Crystal X-ray Diffraction. Furthermore, the pharmacokinetic behavior of TSM-I and TSM-II in rats were measured. We found that though TSM-II is considerably more soluble than TSM-I under water (pH = 7.0) and pH 1.2 buffer conditions, the bioavailability of TSM-Ivia oral administration was better compared to that of TSM-II.

Comparison of the crystal structures and thermochemistry of a novel soluble guanylate cyclase stimulator riociguat and its solvates.

Riociguat (Rio) is the first oral soluble guanylate cyclase stimulator to be approved for pulmonary arterial hypertension. In this study, form (II) of riociguat and three solvates with acetonitrile [form (III)], N,N-dimethylformamide [form (IV)] and ethyl acetate [form (V)] were crystallized. They were identified and characterized by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and their crystal structures were determined by single-crystal X-ray diffraction. No crystal structure has previously been reported for the known form (II) of riociguat. Crystal structure determination of Rio and its new solvates revealed that the dimeric R22(14) motif is common in both structures. The crystal packing of solvates adopts channel-like patterns, whereas form (II) of riociguat adopts sheet-like patterns. Strong π-π interactions exist in the above four forms. The conformation of the riociguat in one molecule of 0.5-DMF solvate was found to be significantly different from the conformations found in the other solvates. Desolvation of the three solvates was studied by thermogravimetric analysis and X-ray diffraction, and was shown to transform them into form (I) of riociguat.

Evaluation of molecular chaperone drug function: Regorafenib and ß-cyclodextrins.

Regorafenib (RG) was an oral multi-kinase inhibitor with poor water solubility. In order to enhance the drug's solubility, dissolution and bioavailability, the binary molecular chaperone drug between RG and ß-cyclodetrin (ß-CD) had prepared by co-crystallization. The structure of RG-ß-CD was characterized by thermal analysis, powder X-ray diffraction, infrared spectroscopy and nuclear magnetic resonance. Phase-solubility study revealed the higher solubility and complexing ability of ß-CDwith RG.The solubility and dissolution of RG-ß-CD was significantly enhanced in pH 1.2 medium, pH 6.8 PBS buffer solution and distilled water compared to RG. In vivo distribution and antitumor studies revealed that the bioavailability of RG-ß-CD was increased when ß-CD mated with RG. Therefore, these findings could provide a suitable pharmaceutical dosage to enhanced therapeutic activity.

Synthesis, characterization and antitumor activity of 5-fluorouracil-nicotinamide cocrystal / 浙江大学学报·医学版

To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.

Crystal structure of vilazodone hydro-chloride methanol monosolvate.

In the title compound, C26H28N5O2+·Cl-·CH3OH {systematic name: 4-(2-carbamoyl-1-benzo-furan-5-yl)-1-[4-(5-cyano-1H-indol-3-yl)but-yl]piperazin-1-ium chloride methanol monosolvate}, the protonated piperazine ring adopts a chair conformation. The indole ring plane is nearly perpendicular to the benzo-furan ring system, with a dihedral angle of 85.77 (2)°. In the crystal, the organic cations, Cl- anions and methanol solvent mol-ecules are linked by classical N-H⋯O and N-H⋯Cl hydrogen bonds, and weak C-H⋯O and C-H⋯π inter-actions into a three-dimensional supra-molecular architecture.