INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 9
·4266
·
IF 4.9
Fumin Xue,Xinyue Yuan,Xingyi Li,Shimin Fang,Yan Cheng
Improving the stability of drugs in the solid state, as well as improving their solubility and poor bioavailability, is highly physiologically relevant. In this study, we focused on enhancing the solubility of hypoxanthine (HYP) through salt formation resulting from the preparation of hypoxanthine–maleic acid salt (HYP-MAL). Single crystals were obtained through solvent evaporation methods, and DSC, TGA, PXRD, FT-IR, and1H NMR spectra were used to characterize the samples. The salt system had higher solubility properties than HYP, with an equilibrium solubility in water that was roughly 2.4 times greater than that of HYP, but the salt’s equilibrium solubility increased when the pH shifted from 7.4 to 1.2; additionally, from 0 to 10 min, the powder dissolution rate was 1.8 times that of HYP, resulting in increased bioavailability. The anti-obesity impact of HYP-MAL salt on obese mice was investigated, providing important insights for the development of future weight-loss medications.
研究领域:
药学
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生物化学
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药物开发
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2024
·
IF 4.3
Fan-Zhi Bu,Su-Su Meng,Ling-Yang Wang,Zhi-Yong Wu,Yan-Tuan Li
In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF’s problems via the salification-driven tactic.
研究领域:
药学
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量子化学
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生物医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF STRUCTURAL CHEMISTRY
·
2025
·Vol. 66
·期 1
·1-15
·
IF 1.4
Ma X.,Yang Y.,Zhou J.,Li Z.,Hong X.,Jin S.,Wang D.
Preparation, X-ray crystal structure, Fourier transform infrared (FTIR) spectroscopy, and elemental analysis of complexes 1 , 2 from the pyridine and the mono- and dicarboxylic acids are reported. XRD and FTIR analysis demonstrate that both belong to the organic salt. The salt 1 crystallizes in the triclinic, space group \(P\bar{1}\) , with a = 7.271(3) Å, b = 9.548(4) Å, c = 14.698(7) Å, α = 78.435(6)°, β = 85.975(7)°, γ = 71.492(6)°, V = 948.0(8) Å 3 , Z = 2. The salt 2 crystallizes in the orthorhombic, space group P 2 1 2 1 2 1 , with a = 7.9476(6) Å, b = 11.6756(9) Å, c = 25.686(2) Å, α = β = γ = 90°, V = 2383.4(3) Å 3 , Z = 4. In this study, the pyridine at 1 , 2 were both involved in the classical ionic N–H⋯O H-bonds. The O–H⋯O H-bonds were also present in both salts. Apart from the classical H-bonds, the auxiliary interactions of CH⋯O, CH 3 –O, CH 3 –CH 3, CH–π, and O–π also helped the stabilization and expansion of the whole high-dimensional (3D) packings. Hirshfeld surface analysis provides additional views into the prevalence of the various short contacts in the crystal structure. On account of the subtle balance of the various nonbonding associations the synthons \(R_{2}^{2}\) (7), \(R_{2}^{2}\) (10), \(R_{3}^{2}\) (8), \(R_{3}^{2}\) (10), \(R_{3}^{3}\) (9), \(R_{3}^{3}\) (19), \(R_{4}^{3}\) (15), \(R_{4}^{4}\) (17), \(R_{5}^{4}\) (12) and \(R_{6}^{4}\) (18) were noted at the salts. For the combination of the classical H-bonds plus the various non-covalent contacts, the salts adopted the 3D net. In conclusion, we have shown that 3D structures can be constructed by the collective non-covalent interactions.
研究领域:
化学
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晶体学
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材料科学
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DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2021
·
IF 3.196
Ronghui Wu,Zhuoran Chen,Xingjun Gao,Xinlei Chen,Shouwen Jin,Li He,Bin Chen,Daqi Wang
Cocrystallization of the ordinarily accessible 4-dimethylaminopyridine (DMAP), with a series of aromatic acids gave a gross of eight anhydrous and hydrous multicomponent molecular salts. The eight salts have been characterised by XRD, IR and EA, their melting points were also reported. Their structural and supramolecular manners are fully evaluated. The result unveils that among all the crystals only the ring N at the DMAP moieties are protonated with the organic acids deprotonated, giving the ion pair. Apart from salt 8 , all the crystal packing is interpreted by the strong charge-assisted N-H⋯O H-bonds from the NH + and the deprotonated acidic groups. The O-H•••O H-bonds were also found at 3 – 8 . All compounds are organic salt, the cation and anion were at 1:1 for 1 – 5 and 7 - 8 , salt 6 has the ratio of 2:1. Further analysis on the crystal packing showed that a different sets of additional CH-N, CH-O/CH 3 -O, CH-S, CH 3 -CH, CH 3 -CH 3 , CH 3 -C π , CH-π/CH 3 -π, I-π, O-S, I-I and π-π contacts contribute to the stabilization and expansion of the total 2D/3D structures. For the synergism of the various weak forces these salts took homo/hetero supramolecular synthons or both.
研究领域:
化学
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材料科学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2021
·
IF 3.196
Wen-Quan Feng,Ling-Yang Wang,Jie Gao,Ming-Yu Zhao,Yan-Tuan Li,Zhi-Yong Wu,Cui-Wei Yan
To improve the physicochemical properties of diclofenac (DFA) and exert its potential anti-tumor effect in combined pharmacotherapy of metformin (MET), a new drug-drug molecular salt of DFA and MET (DFA-MET) is formed and characterized. The single-crystal X-ray diffraction analysis shows that DFA-MET is a three-dimensional (3D) supramolecular structure constructed by different hydrogen-bonding interactions between DFA and MET with 1:1 stoichiometry by proton transfer reaction. In addition, Hirshfeld Surface analysis shows that both the hydrogen-bonding interactions and the Vander Waals maintain the 3D supramolecular structure of DFA-MET together. Compared with pure DFA and pure diclofenac sodium (NaDFA), the dissolving behavior and permeability of DFA-MET by forming drug-drug molecular salt in physiological pH environments are enhanced remarkably.
研究领域:
药学
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生物化学
✓ 已验证
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Min Yu,Jian-Qin Yan,Ling-Yang Wang,Zhi-Yong Wu,Meng-Yao Wu,Yong Sun,Yan-Tuan Li
The codrug efficacy increase approach is developed to improve the biopharmaceutical properties of the conventional antitumor drug 5-fluorouracil (Fu) through molecular salification by tapping the potential of biguanide agents in property optimization and further antitumor synergism. In this route, the biguanide phenformin (Phf) is noncovalently bonded with Fu through a proton transference procedure based on its acidic–alkalinity differences, thereby improving the physicochemical and pharmacokinetic behaviors of Fu and ultimately achieving enhanced efficacy by leveraging the synergized antitumor effect of Phf. Oriented by this, a novel codrug molecular salt, phenforminium 5-fluorouracilate (Fu-Phf), is assembled and systematically characterized for its precise structure employing single-crystal/powder X-ray diffraction and other analytical methods. The results revealed the presence of robust charge-assisted hydrogen bonds in the asymmetric unit, with its structural characteristics being internally hydrophilic and externally hydrophobic, which affects its in vitro physicochemical performances. Thereinto, the dissolubility and permeability of Fu are proven to be simultaneously improved after forming the molecular salt, which aligns positively with a series of theoretical predictions, including molecular electrostatic potential (MEP), reduced density gradient (RDG), frontier molecular orbitals (FMOs), and topological analysis based on the theory of atoms in molecules (AIMs). All of these result in improved in vivo pharmacokinetic performances of the molecular salt, leading to higher bioavailability over Fu alone. Encouragingly, the strengthened tumor inhibition properties of the Fu-Phf codrug are theoretically simulated through the molecular docking method and experimentally observed against selected cancer cell strains, showing significantly reduced IC50. Furthermore, the calculated CI values of less than 1.0 highlight the achievement of the synergistic effects of the two components in the codrug molecular salt. Consequently, this work introduces a fresh salification case of Fu, presenting promising potential for future development; simultaneously, it also provides insights into exploring the possibilities of biguanide medicine as antitumor reinforcement through dual-drug synergy and optimization strategies.
研究领域:
药理学
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肿瘤学
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药物化学
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产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Xin-Ru Zhu,Roudaina Elmidaoui,Yu-Wei Song,Run-Chao Bai,Shuai Wang,Zhao-Hui Ge,Zhi-Long Zhao,Hai-Gang Li,Tong-Tong Zhang,Chun Zhang,Lu Liu
A molecular salt combined with the fluoroquinolone antibacterial gatifloxacin (GAT) and the sulfonamides antibacterial sulfamerazine (SMZ) is designed and synthesized successfully, which is the first report of the dual-drug cocrystallization of gatifloxacin. The precise structure of the acquired molecule salt GAT-SMZ has been characterized via single crystal X-ray diffraction and other techniques. Single crystal diffraction analysis displays that due to the transfer of protons from SMZ to GAT, the molecular salt of GAT-SMZ is formed, and the supramolecular network is dominated by charge-assisted one-dimensional hydrogen bond chain and two-dimensional accumulation layer in the crystal. Such structural feature endows molecular salt with superior physicochemical properties, including enhanced solubility and permeability. More importantly, the superior pharmaceutical performances of the dual-drug salt resulted in enhanced antibacterial activity against the tested strains. These observations are strongly supported by theoretical studies based on Hirshfeld surface and molecular docking analyses. Thus, this contribution not only highlights the validity of combining theory with experiment to drive the problem of physicochemical properties of drugs through co-crystallization methods, but also fills in the previous studies gatifloxacin dual-drug salt synergistic antibacterial research blank.
研究领域:
药物化学
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晶体学
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理论计算
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抗菌研究
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DOI
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Liye Ni,Guangjie Yang,Chenweijia He,Tiancheng Lan,Shuijian He,Haoqi Yang,Nan Wu,Rulan Chen,Li Liu,Fangdi Wu,Qian Zhang
The preparation of porous carbon is constrained by the extensive use and detrimental impact of activators and dopants. Therefore, developing green and efficient strategies that leverage the intrinsic properties and pretreatment of the materials to achieve self-activation and self-doping is particularly crucial for porous carbon materials. Herein, potassium histidine was utilized as the molecular salt precursor, attaining the efficient and streamlined preparation of porous carbon through a one-step carbonization process that enables self-activation, self-doping, and self-templating. More interestingly, the carbonization temperature significantly impacts the porous structure of the molecular salt precursors, the properties of the heteroatoms, and electrochemical performance. The designed electrodes exhibit high accessibility to electrolyte ions and effective ion-electron transport channels. Therefore, the optimal carbon material (KHis800) has an excellent mass-specific capacitance of 305.2 F g–1 at 0.2 A g–1, and a high capacitance retention rate of 115.6% (50,000 cycles at 5 A g–1). Notably, KHis800 also shows a maximum energy density of 19.6 Wh kg–1. This research is dedicated to exploring a more efficient preparation method for porous carbon material via molecular salts, offering insights for the sustainable development of carbon materials.
研究领域:
材料科学
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电化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTENGCOMM
·
2023
·Vol. 25
·期 13
·1951-1964
·
IF 3.1
Fan-Zhi Bu,Yue-Ming Yu,Lin-Lin Zhang,Cui-Wei Yan,Zhi-Yong Wu,Yan-Tuan Li
The goal of the present work is to elucidate the ability of protocatechuic acid (PCA) in downregulating the dissolubility property and gain an innovative insights into conquering adverse reactions of the antifungal drug 5-fluorocytosine (FYT) by a salification strategy. The strategy highlights the feature of adjacent 3,4-substituted phenolic groups on PCA molecule that establishes the helical morphology to attain the hydrophobic molecular salt by facilitating proton exchange reaction between PCA and FTY, thus decreasing FYT's dissolution capacity; moreover, it can also play to PCA's strengths with hepatoprotective effect and antifungal potential as a phenolic acid nutrient, all of which benefit in overcoming the adverse drug reactions caused by the fast and inappropriate absorption of FYT. Taking the strategy as a guideline, the first FTY's molecular salt, FTY–PCA, with hydrophobic characteristics has been successfully synthesized and thoroughly characterized by multiple analytical approaches. The single-crystal X-ray diffraction technology verifies that the newly obtained FTY–PCA consists of an unusual hydrophobic triple helix structure (THS) that is dexterously wound by three strands single helix structure (SHS) via robust hydrogen-bonding interplays and electrostatic forces, which endows the ability of concurrent downregulation of the solubility and dissolution rate, with the maximum reduction being, respectively, 31.23% and 60.49% relative to the parent drug FYT. The experimental outcomes are strongly confirmed by relevant theoretical studies. The molecular electrostatic potential confirms that the THS motif constructed by the SHS forms serves a crucial role in reducing the polarity of the molecular salt and complies with the abatement in polarity, attributable to the reinforced hydrogen-bonding energy as per the electron density difference as well as topology analysis of atoms in molecules, thereby clarifying the hydrophobic property of the molecular salt at theoretical levels. Thereby, the current contribution not only exemplifies the first hydrophobic molecular salt of FYT with a rare triple-helical structure, filling the gaps in the application of hydrophobic molecular salt in antifungal drugs, but also supplies some novel insights into the salinization strategy aiming at overcoming the adverse effects caused by the fast and almost entire absorption of some drugs by ameliorating the dissolubility behaviors.
研究领域:
药学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Energy Materials
·
2023
·Vol. 14
·期 4
·2303020
·
IF 27.8
Simin Chai,Yue Zhong,Yijiang Wang,Qiong He,Alireza Azizi,Leyuan Chen,Xueting Ren,Weifeng Wei,Shuquan Liang,Zhi Chang,Anqiang Pan
Ion electrokinetic regulation in gel polymer electrolytes (GPEs) is of great significance in alleviating dendrite growth and electrode corrosion of metallic lithium in lithium metal batteries (LMBs). Herein, a supramolecular LiPAAOB salt-assisted GPEs (3D-DIS-1.25% GPEs) is synthesized to improve the ionic electrodynamics of LMBs. The LiPAAOB conductor salt provides sufficient Li + ions while simultaneously facilitating LiTFSI dissociation. Theses dissociated Li + ions can be further anchored firmly by enriched affinitive sites (─C═O, ─C─O) induced in 3D composite polymer skeleton (PALC). Due to the strong hydrogen-bonding interactions between PALC and LiPAAOB/LiTFSI, a stable coordination structure is thereby constructed in 3D-DIS-1.25% GPEs, which then facilitates Li + ions to transport rapidly along polymer chains. Consequently, the electrochemical stable window and ionic conductivity of the 3D-DIS-1.25% GPEs are increased to as high as 5.3 V and 1.34 mS cm −1 , respectively. The Li + /e − double conducting interfaces in situ formed on Li metal anode and active particles in cathodes can effectively inhibit dendrite growth and electrode corrosion. As a result, both Li||3D-DIS-1.25% GPEs||Li symmetrical battery and flexible 3D-DIS-1.25% GPEs-based pouch cell with high LFP loading operate stably even under folded and curly state, indicating the application possibility of using 3D-DIS-1.25% GPEs in constructing various flexible high-energy-density batteries.
研究领域:
材料科学
·
电化学
·
能源存储
✓ 已验证
DOI
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Liye Ni,Guangjie Yang,Chenweijia He,Tiancheng Lan,Ping Li,Haoqi Yang,Li Liu,Yongshuo Peng,Shuijian He,Qian Zhang
The incompatibility between electrolyte ions and electrode pore sizes, coupled with the extensive use of activators and dopants, significantly restricts the fabrication of porous carbon materials. Consequently, developing environmentally sustainable and efficient methodologies that exploit the intrinsic properties and pretreatment of materials to facilitate self-activation and self-doping becomes crucial. In this study, potassium histidine and magnesium histidine molecular salts were synthesized as precursors, enabling specific ion activation and bimetallic template-directed tunable porosity through a one-step carbonization process. Notably, the ratio of bimolecular salts significantly influenced the porous structure of carbon, the properties of heteroatoms, and the electrochemical performance. By optimizing the ratio, the porous carbon materials exhibited high accessibility to electrolyte ions and effective ion/electron transport channels. Consequently, the optimal sample (NOSPC-2) achieved a high specific capacitance of 318 F g–1 at 0.1 A g–1 and a good capacitance retention rate of 98.8% after 50,000 cycles at 5 A g–1. In addition, NOSPC-2 also boasted high energy density and power density, reaching 22 Wh kg–1 and 25 kW kg–1, respectively. This research represents a significant stride in advancing preparation technologies for small molecule derived porous carbon materials, providing valuable insights for the rational design of carbon electrode materials for capacitive energy storage.
研究领域:
材料科学
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能源存储
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Ling-Yang Wang,Fan-Zhi Bu,Yue-Ming Yu,Yuan-Yuan Niu,Yan-Tuan Li,Cui-Wei Yan,Zhi-Yong Wu
In order to exploit the advantages to the full of multidrug salification strategy in amending the pharmaceutical properties of drugs both in vitro and in vivo , and further to open up a new way for its applications in bacteria-virus mixed cross-infection drugs, a novel dual-drug crystalline molecular salt hybridizing antibacterial drug sulfamethoxazole (SFM) with antiviral ingredient amantadine (ATE), namely SFM-ATE, is successfully designed and synthesized via multidrug salification strategy oriented by proton exchange reaction. The crystal structure of the firstly obtained molecular salt is precisely identified by employing single-crystal X-ray diffraction and multiple other techniques. The results show that, in the crystal lattice of molecular salt SFM-ATE, the classical hydrogen bonds together with charge-assisted hydrogen bonds contribute to two- dimensional networks, between which the hydrophobic interaction plays an important role. The relevant in vitro/vivo pharmaceutical properties of the dual-drug molecular salt are carried out through a comparative investigation of theoretical and experimental methods. It has been found that SFM displays concurrent improvements over the bulk drug in its permeability and dissolution after forming the molecular salt, which is supported by the molecular electrostatic potential calculation and Hirshfeld surface analysis. Encouragingly, the perfected in vitro biopharmaceutical properties can effectually turn into the in vivo pharmacokinetic preponderances with the expedited peak plasma concentration, lengthened half-life and enhanced bioavailability. Better yet, the antibacterial activities of SFM from the molecular salt get stronger with enlargement in inhibition areas and reduction in values of minimum inhibitory concentrations against the tested bacterial strains. Consequently, the present contribution not only supplies an opportunity for widening applications for classical sulfa drugs via dual-drug salification strategy, but also offers an alternative approach in dealing with viral-bacterial coinfection even other complex diseases by drugs’ hybridization at the molecular level.
研究领域:
药学
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生物化学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）