Synthesis and Characterization of Novel pH-Responsive Aminated Alginate Derivatives Hydrogels for Tissue Engineering and Drug Delivery.

AIMS: The aims of this study are to synthesize new derivatives of sodium alginate that improve the inherent properties, such as hydrogel strengthening, and create environmental sensitivity, such as pH sensitivity, for use in drug delivery. BACKGROUND: Today, hydrogels, due to outstanding properties such as biodegradability, biocompatibility, mechanical properties, and response to stimuli properties, are widely used as harmless biomaterials in various fields in drug delivery, wound dressing, and tissue engineering. Stimulus-sensitive polymers significantly respond to slight changes in their environment. Different types of stimuli are used to influence the properties of polymers, the most important of which are temperature and pH because these are two vital factors in the human body; hence, temperature-sensitive and pHsensitive hydrogels have been extensively studied. The ability to absorb water and swell the hydrogel is due to hydrophilic chains in the hydrogel network, and water absorption by hydrogel can be controlled by response to the stimuli. Since hydrogels mimic human tissue, the ability to retain water in them is essential. As a result, it is considered in many biomedical drug delivery systems. Stimulusresponsive swelling can control diffusion out of and into the hydrogel network, which allows temporal and spatial control of drug release. When a drug is loaded onto a biodegradable and stimulisensitive hydrogel, the drug delivery system has the added advantage of sustained release of the drug, which reduces side effects. METHODS: In this study, two different hydrocarbons, [1,3-diaminopropane (DAP)] as a short-chain hydrocarbon, and [1,7-diaminoheptane (DAH)] as a long-chain hydrocarbon were grafted onto three types ofsodium alginate (SA), through amide bond linkages. The hydrogel copolymer matrices were compared with sodium alginate (SA) beads. The graft copolymers were characterized using FTIR, 1HNMR, XRD spectroscopy, elemental analysis (CHNS) and thermal analysis (TGA, DTA and DSC). An environmental scanning electron microscope (ESEM) was used to investigate the surface morphology of hydrogels. RESULTS: Effects of variables such as the length of hydrocarbon chains cross-linked to alginate, temperature, pH, and cross-linkers on the properties of hydrogels investigated in the temperature range of 2-70 ˚C and two different pH values (4.4 and 7.4). The results showed that when the hydrocarbon chain length of diamines decreases, the extent of cross-linking and strength of the hydrogels are increased. Other results suggest that the hydrogels obtained from high-viscosity alginate derivatives had positive pH sensitivity. Hydrogels prepared in this study demonstrated good mechanical and swelling ratios that are necessary for wound dressing. CONCLUSION: DAP-g-SA and DAH-g-SA pH-sensitive hydrogels were successfully synthesized through amide bond linkages. The new synthesis derivatives showed lower swelling levels at low pH (4.4). In contrast, their swelling levels at higher pH (7.4) were significantly enhanced. Higher swelling degree could be obtained at high pH. pH-responsive hydrogels are especially useful for various biological applications due to their unique feature of controlled swelling, biodegradability, biocompatibility, and fluid retention in their network structures. pH-responsive hydrogels, as intelligent systems, can be used in controlled-release drug delivery systems such as insulin delivery.

Electro-organic synthesis of tetrahydroimidazo[1,2-a]pyridin-5(1H)-one via a multicomponent reaction.

Electro-synthesis through a one-pot three-component condensation of corresponding aldehydes, Meldrum's acid, and 2-(nitromethylene)imidazolidine resulted in a series of novel tetrahydroimidazo[1,2-a]pyridine-5(1H)-one derivatives containing an electronegative pharmacophore (=CNO2). The process was carried out in propanol medium with sodium bromide presented as electrolyte, inside an undivided cell with good to excellent yields. As a powerful entry into fused polycyclic structures related to bioactive heterocycles, this green protocol shows great potential.

Organocatalytic Combinatorial Synthesis of Quinazoline, Quinoxaline and Bis(indolyl)methanes.

AIMS AND OBJECTIVE: An efficient and practical procedure for the synthesis of heterocyclic compounds such as quinazolines, quinoxalines and bis(indolyl)methanes was developed using 3,5-bis(trifluoromethyl) phenyl ammonium hexafluorophosphate (BFPHP) as a novel organocatalyst. MATERIALS AND METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR, 13CNMR and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: The BFPHP organocatalyst demonstrates a novel class of non-asymmetric organocatalysts, which has gained much attention in green chemistry.

Alignment-independent 3D-QSAR and molecular docking studies of tacrine-4-oxo-4H-Chromene hybrids as anti-Alzheimer's agents.

A series of novel tacrine derivatives as multifunctional agents with potential inhibitory effects on both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes for the treatment of Alzheimer's disease(AD), were applied to alignment independent 3D-QSAR methods using Pentacle software. In this studies, GRID-independent molecular descriptors (GRIND) analysis have been applied to characterize important interactions between enzymes and the studied compounds. Two H-bond acceptor groups as well as hydrophobic properties of tacrine rings for AChE and two H-bond acceptor on the carbonyl group of chromene and NH of amid group for BuChE, with positive effects on their inhibitory potency have been identified. The obtained 3D-QSAR models have been analyzed and validated. The statistical quality of the QSAR model for AChE, r2 = 0.87, q2 = 0.56 and for BuChE, r2 = 0.96, q2 = 0.70 was resulted. Using these models, novel structures have been designed and pIC50 of them were predicted. Molecular docking studies were also conducted on AChE (1ACJ) and BuChE (4BDS) and promising results in good agreement with 3D-QSAR studies were obtained.

Solvent-mediated Highly Efficient Synthesis of [1,2,4]triazolo/benzimidazoloquinazolinone Derivatives.

OBJECTIVE: An efficient and catalyst-free procedure for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones has been developed in 2,2,2-trifluoroethanol or deep eutectic solvent(DESs) as a clean reaction media. METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR,13CNMR, and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: We have efficiently developed a practical and catalyst-free approach for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones employing TFE as a clean and reusable media.

Highly sensitive detection of Ceftriaxone in water, food, pharmaceutical and biological samples based on gold nanoparticles in aqueous and micellar media.

A colorimetric assay with excellent sensitivity is reported to detect Ceftriaxone in aqueous and micellar solutions. Ceftriaxone could induce the aggregation of gold nanoparticles through hydrogen-bonding interaction and electrostatic attraction. As a result of aggregation, the surface plasmon resonance band around 520 nm decreases and a new band appears at 620 nm. The effect of surfactants was investigated on the aggregation. The band around 620 nm is shifted to around 685 nm in Triton X-100 micellar media and that is seen color conversion from red to deep blue which is clearly detectable by the naked eye. The results were improved in Triton X-100 micellar media as compared to aqueous media so that the lowest measured concentration and detection limit in micellar media have decreased 10 and 8 times, respectively. Triton X-100 showed strong effect on the stabilization of the solutions. The method has been successfully applied for the analysis of various real samples.