Crystal Growth & Design最新文献

{"title":"A Coordination-Catalyzed Multistep Tandem Reaction Constructs Hexanuclear Dysprosium Clusters with a Misaligned Double-Layer Triangular Shape Composed of Complex Acetal Trimers","authors":"De-Xin Chen,&nbsp;Ju-Fen Ai,&nbsp;Lin-Qian Li,&nbsp;Hai-Ling Wang,&nbsp;Hua-Hong Zou* and Zhong-Hong Zhu*,&nbsp;","doi":"10.1021/acs.cgd.5c0038410.1021/acs.cgd.5c00384","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00384https://doi.org/10.1021/acs.cgd.5c00384","url":null,"abstract":"<p >It is extremely challenging to rapidly and efficiently generate complex organic polymers from very simple industrial raw materials through coordination-driven multistep tandem reactions under “one-pot” conditions. Herein, simple industrial raw materials, <i>o</i>-vanillin derivatives, 2-amino-1,2-diphenylethanol, and Dy(NO₃)₃·5H₂O, were used to react under “one-pot” solvothermal conditions to form complex acetal trimers, and dislocated double-layer triangular hexanuclear clusters <b>1</b> and <b>2</b>, formed by the above trimers chelating Dy(III) ions, were obtained. The complex acetal trimer chelating ligands within clusters <b>1</b> and <b>2</b> are formed by a coordination-catalyzed multistep tandem reaction of <i>o</i>-vanillin derivatives with 2-amino-1,2-diphenylethanol. In the abovementioned tandem reaction process, the Schiff base reaction first occurs to form an imine intermediate, followed by a multistep acetal reaction to finally form an acetal trimer chelating ligand. The abovementioned hexanuclear clusters are composed of two parallel and staggered triangular Dy₃ clusters, the <i>o</i>-vanillin derivative (second ligand), the terminal coordinated NO₃^–, and the in situ formed acetal trimer in the structure are all arranged in antiparallel. It is worth noting that clusters <b>1</b> and <b>2</b> both showed distinct single-molecule magnet (SMM) behavior under zero-field conditions, with their effective energy barriers and magnetic relaxation times being <i>U</i>_eff = 9.2 K and 92.7 K, τ₀ = 8.6 × 10^–5 s and 8.8 × 10^–8 s, respectively. Coordination-catalyzed tandem reactions enrich the synthesis strategies of complex organic compounds, avoiding multistep organic synthesis and purification steps that require complex operations and provide low yields. They have the advantages of being fast, simple, efficient, and having high atomic utilization. This work utilized a complex in situ tandem reaction assisted by Dy(III) ion coordination to obtain hexanuclear dysprosium clusters with SMM behavior, which not only promoted the progress of crystal engineering of lanthanide clusters but also opened a door to the synthesis of magnetic crystalline materials constructed by complex organic chelating ligands.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3555–3562 3555–3562"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switchable Magnetic Properties in a Hydrogen-Bonded Cobalt(II)-Organosulfonate Framework via Reversible Dehydration–Hydration","authors":"Fu-Wan Dong,&nbsp;Yi Chen,&nbsp;Qi-Juan Cai,&nbsp;Lu-Yao Ma,&nbsp;Jiong Yang,&nbsp;Le Shi,&nbsp;Junlun Zhu and Dong Shao*,&nbsp;","doi":"10.1021/acs.cgd.5c0030510.1021/acs.cgd.5c00305","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00305https://doi.org/10.1021/acs.cgd.5c00305","url":null,"abstract":"<p >Dynamic modulation of magnetic properties through single-crystal-to-single-crystal (SC–SC) transformations has always been difficult. In this study, we present a hydrogen-bonded cobalt(II)-organosulfonate framework exhibiting reversible dehydration–hydration switching of magnetic properties, accompanied by SC–SC transformation. Notably, a subtle structural transformation induced by dehydration–hydration triggers three key modifications: (1) significant geometric distortion at the Co²⁺ center, (2) rotational reorientation of bridging ligands, and (3) reorganization of the hydrogen-bonding network. These structural changes manifest in remarkable macroscopic property modulations, including a naked-eye-detectable color transition from yellow to pink, switching between weak antiferromagnetic coupling states, and on–off switching of the single-ion magnet (SIM) property. Our findings establish an effective strategy for modulating SIM property in coordination polymers through controlled structural reorganization within a 3D hydrogen-bonded organosulfonate framework.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3464–3470 3464–3470"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FeIII Spin Crossover Complexes with a Dual-Substituted Hqsal Ligand: Anion, Solvent, and Pressure Effects","authors":"Xin-Li Liu,&nbsp;Yue Zhao,&nbsp;Tianwei Wang,&nbsp;Peng Wang,&nbsp;Gang Li,&nbsp;Bo-Hong Gao,&nbsp;Xiao-Lei Zhang and Xin-Yi Wang*,&nbsp;","doi":"10.1021/acs.cgd.5c0033510.1021/acs.cgd.5c00335","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00335https://doi.org/10.1021/acs.cgd.5c00335","url":null,"abstract":"<p >Three Fe^III complexes featuring a new qsal-type ligand with substitutions on both the quinoline and benzene rings, [Fe(5-CH₃-qsal-5-Br_q)₂]A·sol (A = NO₃^–, sol = CH₃OH <b>1-a</b> and <b>1-b</b>; and A = OTf^–, sol = 1.3CH₃OH <b>2</b>, 5-CH₃-qsal-5-Br_q = <i>N</i>-(5-Bromo-8-quinolyl)-5-methyl-salicylaldimine), were synthesized and characterized. Isomers <b>1-a</b> (kinetically stable) and <b>1-b</b> (thermodynamically stable) coexist in varying ratios in different batches, influenced by evaporation time. Isomer <b>1-a</b> and complex <b>2</b>, both with one unique Fe^III center, exhibit similar Chain-Layer structures, whereas isomer <b>1-b</b>, with two unique Fe^III centers, shows slight difference. The different stabilities and ratios of the isomers result in different spin crossover performances with varying high spin proportions across different batches of sample <b>1</b>. Solvent effects on spin crossover properties were examined for all complexes. For <b>1-a</b> and <b>1-b</b>, desolvation leads to a transition from spin crossover behavior to a high spin state, whereas in complex <b>2</b>, it induces a transition from high spin to spin crossover. A solvent exchange from methanol to water at room temperature leads to the hydrated form <b>1-b(H</b>_<b>2</b><b>O)</b>, which always stays in the high spin state. Progressive desolvation of complex <b>2</b> induces a gradual transition from a pure high spin state to an incomplete spin crossover with hysteresis loops, ultimately leading to a nearly complete spin crossover with minimal loops. Pressure effects have also been examined, showing stabilization of the low spin state for both complexes.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3518–3528 3518–3528"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Pressure Polymorphism of Ribavirin.","authors":"Bhaskar Tiwari, Hanns-Peter Liermann, Simon Parsons, Nico Giordano","doi":"10.1021/acs.cgd.5c00372","DOIUrl":"10.1021/acs.cgd.5c00372","url":null,"abstract":"<p><p>The effect of high pressure on ribavirin, a broad-spectrum antiviral consisting of ribofuranosyl triazole, and carboxamide moieties, has been studied up to ∼10 GPa. Three new high-pressure phases, designated <b>V3</b>, <b>V4</b> and <b>V5</b>, have been obtained by compression of the ambient-pressure <b>V2</b> form with structures refined up to 7.5 GPa. The new phases are formed at 5.3, 6.0, and 7.2 GPa, respectively, and crystallize in space group <i>P</i>2₁2₁2₁ with <i>Z</i>' = 3, 1, and 1. They are distinguished by changes in the conformation of the ribofuranosyl moiety which impacts both the molecular geometry and the supramolecular structure.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3537-3547"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substrate-Directed Deposition of 3R–NbS2 Nanocrystals with a Bottom-Up Approach","authors":"Nour Abdelrahman*,&nbsp;Solveig Marit Oelke,&nbsp;Samuel Froeschke,&nbsp;Daniel Wolf,&nbsp;Bernd Büchner,&nbsp;Michael Mertig and Silke Hampel*,&nbsp;","doi":"10.1021/acs.cgd.5c0033210.1021/acs.cgd.5c00332","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00332https://doi.org/10.1021/acs.cgd.5c00332","url":null,"abstract":"<p >Niobium disulfide is a member of the metallic two-dimensional layered transition metal dichalcogenides (TMDs) family with a thermodynamically stable 3R-structure. Despite the difficulties involved in controlling the growth of NbS₂ crystals with a well-defined structure, a rational approach of bottom-up synthesis of NbS₂ nanostructures was performed to achieve this. The parameters of the synthesis by chemical vapor transport (CVT) were derived by thermodynamic simulations of the reaction pathway according to TRAGMIN. High-quality 3R NbS₂ nanocrystals were successfully deposited directly on thermal-oxidized Si/SiO₂ (100) and thermal-oxidized C-plane sapphire substrates. By using short time vapor transport (0.5 h) and addition of iodine in the temperature range between 600 and 800 °C, a thickness down to 7 nm (∼12 layers) was achieved. The high-crystallinity morphology of the deposited nanocrystals was confirmed by high-resolution transmission electron microscopy, selected area electron diffraction, and atomic force microscopy as well as double-polarized Raman spectroscopy. Our work explores an important synthesis route to obtain a well-determined phase structure, which is a crucial factor to be considered if practical applications should be realized in the future.</p><p >Thermodynamically controlled growth of high-quality, phase-pure 3R–NbS₂ nanocrystals via chemical vapor transport enables advances in two-dimensional materials applications.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3529–3536 3529–3536"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.5c00332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Pressure Polymorphism of Ribavirin","authors":"Bhaskar Tiwari,&nbsp;Hanns-Peter Liermann,&nbsp;Simon Parsons* and Nico Giordano*,&nbsp;","doi":"10.1021/acs.cgd.5c0037210.1021/acs.cgd.5c00372","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00372https://doi.org/10.1021/acs.cgd.5c00372","url":null,"abstract":"<p >The effect of high pressure on ribavirin, a broad-spectrum antiviral consisting of ribofuranosyl triazole, and carboxamide moieties, has been studied up to ∼10 GPa. Three new high-pressure phases, designated <b>V3</b>, <b>V4</b> and <b>V5</b>, have been obtained by compression of the ambient-pressure <b>V2</b> form with structures refined up to 7.5 GPa. The new phases are formed at 5.3, 6.0, and 7.2 GPa, respectively, and crystallize in space group <i>P</i>2₁2₁2₁ with <i>Z</i>′ = 3, 1, and 1. They are distinguished by changes in the conformation of the ribofuranosyl moiety which impacts both the molecular geometry and the supramolecular structure.</p><p >We report multiple high-pressure phase transitions of the <b>V2</b> form of ribavirin due to conformational flexibility in its ribofuranosyl ring. Changes in the ring conformation affect the molecular geometry and the supramolecular structure and are described in terms of a pseudorotation pathway.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3537–3547 3537–3547"},"PeriodicalIF":3.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.5c00372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphology-Selective Copper Aluminum-Layered Double Hydroxide Nanoflowers for Enhanced Photocatalytic Degradation of Tetracycline Hydrochloride","authors":"Enlei Zhang*,&nbsp;Xiaowen Song,&nbsp;Jiaojiao Chen,&nbsp;Renzheng Jiang,&nbsp;Bengui Zhang,&nbsp;Yingpeng Xie and Guosheng Wang,&nbsp;","doi":"10.1021/acs.cgd.5c0031010.1021/acs.cgd.5c00310","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00310https://doi.org/10.1021/acs.cgd.5c00310","url":null,"abstract":"<p >Copper aluminum double hydroxide nanocrystallines with different morphologies for the efficient photocatalytic degradation of tetracycline hydrochloride (TC-HCl) were synthesized successfully by a facile water bath method. The morphology and crystal structure of the products were analyzed by using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), etc. Morphologies of copper aluminum double hydroxide nanocrystallines have an effect on the size of their band gap and photocatalytic performance. Copper aluminum-layered double hydroxide (CuAl-DLH) nanoflowers were utilized in the photocatalytic degradation of TC-HCl, and they showed better excellent catalytic performance and recyclability than others. The effects of the catalyst mass, H₂O₂ content, TC-HCl initial concentration, pH, and reaction temperature on the photocatalytic degradation of TC-HCl with Cu₃Al₁-LDH nanoflowers were examined. Cu₃Al₁-LDH nanoflowers showed good catalytic performance with a TC-HCl degradation rate of 93% at room temperature in 60 min. After five cycles of reuse, the TC-HCl degradation rate of Cu₃Al₁-LDH nanoflowers was still above 85%, indicating that Cu₃Al₁-LDH nanoflowers have good stability and repeatability. Finally, the mechanisms of photocatalytic degradation on Cu₃Al₁-LDH nanoflowers are also discussed. The synthesized innovative Cu₃Al₁-LDH nanoflowers have great potential in the area of antibiotic pollutant destruction.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3471–3480 3471–3480"},"PeriodicalIF":3.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal-Chemical Design of Hydroxyapatite Magnetic Nanoparticles with Transition Metals","authors":"Anatolii V. Korneev*,&nbsp;Elena S. Sergienko,&nbsp;Maria A. Kuz’mina,&nbsp;Andrey A. Pavlychev,&nbsp;Xenia O. Brykalova,&nbsp;S. Narayana Kalkura and Olga V. Frank-Kamenetskaya,&nbsp;","doi":"10.1021/acs.cgd.5c0031310.1021/acs.cgd.5c00313","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00313https://doi.org/10.1021/acs.cgd.5c00313","url":null,"abstract":"<p >Incorporation of transition metals into hydroxyapatite (HAp) is a way to fabricate biocompatible magnetic nanoparticles (MNPs) for biomedical applications such as cancer hyperthermia and drug delivery. To develop a crystal-chemical design of HAp MNPs, a series of HAps doped with 3d elements (Mn, Fe, Co, Zn, Ni) were synthesized from aqueous solutions and studied using a wide set of methods, including powder X-ray diffraction (PXRD), vibrational spectroscopy, energy-dispersive X-ray (EDX) analysis, electron paramagnetic resonance (EPR), Mössbauer spectroscopy, X-ray photoelectron spectroscopy (XPS), SQUID magnetometry, and magnetic susceptibility measurements. It was shown that the limiting concentrations of all studied transition metals in HAp, and the concentrations beyond which HAp does not crystallize, are directly dependent on the proximity of the ionic radii of the dopants to Ca²⁺ radius: Ca²⁺ &gt; Mn²⁺ &gt; Fe²⁺ &gt; Co²⁺ &gt; Zn²⁺ &gt; Ni²⁺ &gt; Fe³⁺. Doping of HAp with cations containing unpaired electrons in the 3d orbital (Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺) leads to a diamagnetic–paramagnetic transition. The weak ferromagnetic or antiferromagnetic behavior of the synthesis products at cryogenic temperatures most likely originates from 3d-oxide impurities. The magnetic susceptibility of 3d-HAps, which is one of the key parameters of MNPs, is directly dependent not only on the number of unpaired electrons but also on the 3d element content in the HAp lattice. Discovered correlations between magnetic susceptibility and the crystal chemistry of HAp contribute to the development of directed synthesis of HAp MNPs with the required magnetic properties. HAp doped with ∼10 wt % Mn²⁺ with a magnetic susceptibility of ∼4.2 × 10^–5 emu/g, is the most promising candidate for MNPs for biomedical applications.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3481–3496 3481–3496"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixed Electrolyte or Single Salt Solution–Is There an Impact of Precipitating Salts on the Damage Potential? Investigations on the Na+–K+–Cl––NO3––H2O System","authors":"Amelie Stahlbuhk*,&nbsp; and ,&nbsp;Michael Steiger,&nbsp;","doi":"10.1021/acs.cgd.5c0032310.1021/acs.cgd.5c00323","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00323https://doi.org/10.1021/acs.cgd.5c00323","url":null,"abstract":"<p >Salt damage to porous building materials, which becomes relevant in case of high pore fillings and cyclic crystallization events, affects numerous objects of our cultural heritage. For single salts, the critical threshold values for crystallization cycles are given by the deliquescence humidity and the crystallization humidity, the latter depending on the degree of supersaturation prior to crystallization. Contamination of built heritage with only one single salt is unlikely, so ion mixtures must be considered for a more realistic assessment of the damage potential. For salt mixtures, the boundary conditions, i.e., crystallization humidities and the relative humidity range relevant for crystallization and dissolution processes, are different from the conditions for single salts. This paper investigates whether the damage potential of a salt is also different when precipitating from a mixture rather than from its pure solution. For that purpose, the supersaturation by cooling and by evaporation is used as a measure for the damage potential and is determined for different systematically selected mixture compositions of the Na⁺–K⁺–Cl^––NO₃^––H₂O system and respective subsystems. The results indicate that the supersaturation of some salts is indeed affected by accompanying ions, while for others, the impact is low.</p><p >This study examines how the mixture composition in the Na⁺−K⁺−Cl⁻−NO₃⁻−H₂O system affects the damage potential of salts by investigating supersaturation. It was found that accompanying ions systematically affect the supersaturation levels of some precipitating salts and that mixed electrolytes may pose different risks than binary solutions, demonstrating the relevance of their investigation.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3497–3510 3497–3510"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.5c00323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Mechanistic Shortcomings of Acetazolamide Cocrystals in Harnessing the Anticipated Solubility and Permeability Advantages","authors":"Noopur Pandey,&nbsp;Aastha Tiwari,&nbsp;Sudeshna Kundu,&nbsp;Susanta Kumar Mondal,&nbsp;Adam A. L. Michalchuk,&nbsp;Nimmy Kumari,&nbsp;Parag Roy,&nbsp;Kenjirou Higashi*,&nbsp;Alok Jain* and Animesh Ghosh*,&nbsp;","doi":"10.1021/acs.cgd.5c0024410.1021/acs.cgd.5c00244","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00244https://doi.org/10.1021/acs.cgd.5c00244","url":null,"abstract":"<p >The previously reported pharmaceutical cocrystals of acetazolamide (ACZ) with highly soluble and lipophilic coformers, including 4-hydroxybenzoic acid (4HBA), salicylamide (SAL), and 4,4′-bipyridine (BIPY), were investigated to enhance the solubility and permeability profiles of ACZ. However, <i>in vitro</i> solubility and dissolution studies revealed that the cocrystals exhibited minimal to no advantage over their respective physical mixtures and/or pure ACZ. To elucidate the underlying mechanism, lattice energy calculations were performed, demonstrating that the high lattice stability of the cocrystals restricted solubility and dissolution enhancement. Additionally, solution-state ¹H NMR spectra confirmed that cocrystals and physical mixtures exhibit similar molecular states, further explaining the lack of solubility and dissolution improvement. Caco-2 permeability studies of cocrystals and the pure drug indicated no significant enhancement in ACZ permeability, which was supported by <i>in silico</i> molecular dynamics simulations showing unchanged stability of the ACZ-efflux transporter complex in the presence of coformers. These findings emphasize the limitations of conventional coformer selection strategies and highlight the necessity for predictive tools in pharmaceutical cocrystal design. This study proposes an <i>in combo</i> predictive model to predict cocrystal properties before synthesis, reducing trial-and-error approaches.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 10","pages":"3425–3440 3425–3440"},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}