Novel Stimuli-Responsive Pectin-PVP-Functionalized Clay Based Smart Hydrogels for Drug Delivery and Controlled Release Application

Stimuli-responsive drug delivery systems are urgently required for injectable site-specific delivery and release of drugs in a controlled manner. For this purpose, we developed novel pH-sensitive, biodegradable, and antimicrobial hydrogels from bio-macromolecule pectin, polyvinylpyrrolidone (PVP), 3-aminopropyl (diethoxy)methyl silane (3-APDEMS), and sepiolite clay via blending and solution casting technique. The purified sepiolite (40 um) was functionalized with 3-APDEMS crosslinker (ex-situ modification) followed by hydrogels fabrication. FTIR and SEM confirmed crosslinked structural integrity and rod-like morphology of hydrogels respectively. The swelling properties of hydrogels could be controlled by varying the concentration of modified clay in pectin/PVP blends. Moreover, the decrease in pH increased the swelling of hydrogels indicating the pH-responsiveness of hydrogels. All hydrogels were degraded after 21 days in phosphate buffer saline pH 7.4 (human blood pH). In-vitro cytotoxicity against 3T3 mouse fibroblast cell line analysis confirmed cytocompatibility of all hydrogels. Ceftriaxone sodium (CTX-S) was selected as a model drug. The release profile of the hydrogel showed 91.82% release in PBS for 2 h in a consistent and controlled manner. The chemical structure of the drug remained intact during and after release confirmed through UV-Visible spectroscopy. Overall, these hydrogels could be used as potential scaffolds for future biomedical applications

Relevant p-hole tetrel bonding interactions in ethyl 2-triazolyl-2-oxoacetate derivatives: Hirshfeld surface analysis and DFT calculations

This manuscript reports the synthesis, spectroscopic and X-ray characterization of four triazole derivatives that include an α-ketoester functionality and two phenyl substituents. In particular ethyl 2-(4-(4-chlorophenyl)-1-(4-methylbenzyl)- 1H-1,2,3-triazol-5-yl)-2-oxoacetate (1), ethyl 2-(1-(4-methylbenzyl)-4-phenyl-1H-1,2,3- triazol-5-yl)-2-oxoacetate (2), ethyl 2-(1-benzyl-4-(3-fluorophenyl)-1H-1,2,3-triazol-5- yl)-2-oxoacetate (3) and ethyl 2-(1-benzyl-4-(4-methoxyphenyl-1H-1,2,3-triazol-5-yl)-2- oxoacetate (4) were synthesized in good yields. All compounds form self-assembled dimers in the solid state establishing two symmetrically equivalent O···π-hole tetrel bonding interactions. These interactions have been analyzed using Hirshfeld surface analysis, DFT calculations and the Bader’s theory of atoms-in-molecules and further rationalized using the molecular electrostatic potential (MEP) surface calculations. We have studied how the nucleophilic/electrophilic nature of the –COOEt and –CO– groups is affected by the substituents of the rings and, consequently, influences the interaction energy of the C···O tetrel bond.Fil: Ahmed, Muhammad Naeem. University of Azad Jammu and Kashmir; PakistánFil: Yasin, Khawaja Ansar. University of Azad Jammu and Kashmir; PakistánFil: Aziz, Shahid. Mirpur University of Science And Technology; PakistánFil: Khan, Saba Urooge. University of the Punjab; PakistánFil: Tahir, Muhammad Nawaz. University of Sargodha; PakistánFil: Gil, Diego Mauricio. Universidad Nacional de Tucumán. Instituto de Biotecnología Farmacéutica y Alimentaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biotecnología Farmacéutica y Alimentaria; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; ArgentinaFil: Frontera, Antonio. Universidad de las Islas Baleares; Españ

Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement

Considering the astounding biomedicine properties of pharmaceutically active drug, 4-aminophenazone, also known as 4-aminoantipyrine, the work reported in this manuscript details the formation of novel cocrystals of rearranged 4-aminophenazone and 4-nitro-N-(4-nitrobenzoyl) benzamide in 1:1 stoichiometry under employed conditions for thiourea synthesis by exploiting the use of its active amino component. However, detailed analysis via various characterization techniques such as FT-IR, nuclear magnetic resonance spectroscopy and single crystal XRD, for this unforeseen, but useful cocrystalline synthetic adduct (4 and 5) prompted us to delve into its mechanistic pathway under provided reaction conditions. The coformer 4-nitro-N-(4-nitrobenzoyl) benzamide originates via nucleophilic addition reaction following tetrahedral mechanism between para-nitro substituted benzoyl amide and its acid halide (1). While the enamine nucleophilic addition reaction by 4-aminophenazone on 4-nitrosubstituted aroyl isothiocyanates under reflux temperature suggests the emergence of rearranged counterpart of cocrystal named N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carbonothioyl)-4-nitrobenzamide. Crystallographic studies reveal triclinic system P-1 space group for cocrystal (4 and 5) and depicts two different crystallographically independent molecules with prominent C-H center dot center dot center dot O and N-H center dot center dot center dot O hydrogen bonding effective for structure stabilization. Hirshfeld surface analysis also displays hydrogen bonding and van der Waals interactions as dominant interactions in crystal packing. Further insight into the cocrystal synthetic methodologies supported the occurrence of solution-based evaporation/cocrystallization methodology in our case during purification step, promoting the synthesis of this first-ever reported novel cocrystal of 4-aminophenazone with promising future application in medicinal industry