This research investigates applying zinc oxide (ZnO) nanoparticles (NPs) as inorganic nanofillers to poly(amide-imide) (PAI) as a polymer matrix via ultrasound technique for the preparation of PAI/ZnO bionanocomposites (BNCs). The surface of ZnO NPs was successfully treated with γ-methacryloxypropyltrimethoxysilane coupling agent (KH570) to decrease the hydrophilicity of NPs. The optically active PAI containing natural L-leucine amino acid was synthesized in a green solvent system which is consisted of tetrabutyl ammonium bromide/triphenyl phosphate. The influences of the ZnO on the structure, morphology, thermal, and optical properties of BNCs were, respectively, characterized by several techniques. All the results indicate that NPs are successfully modified and are compatible with polymer matrix and also proved that there is a homogenous dispersion of ZnO NPs in the polymer matrix in nanoscale.
Epimerization and recycling of an unwanted piperazine stereoisomer enabled a more sustainable, concise, and high-yielding synthesis of a chiral adagrasib building block. The unselective bond formation thus resembled a formal enantioselective aza-Michael reaction. This strategy shortened development timelines, eliminated the handling of sodium cyanide, removed two chemical bond-forming operations, and decreased the process mass intensity nearly 3-fold. The overall yield was improved from 34 to 74%. Widely available commodity chemicals were selected as building blocks.
Process optimization details are disclosed following the completion of process design for a second-generation manufacturing route of adagrasib. Key objectives for development included control of difficult-to-purge impurities in the key starting materials (KSMs), enhanced scalability of the KSM, improved pyrimidone formation of the core, increased robustness of oxidation, enhanced stability of the step 3 intermediate, removal of the halogenated solvent in the fourth step, and implementation of single crystallization of the final API. These improvements led to more efficient production of adagrasib and a further reduction in the cost of goods by approximately 50%.
The widespread application of 1,2,3-triazoles in pharmaceuticals has resulted in substantial interest toward developing efficient postmodification methods. Whereas there are many postmodification methods available to obtain N1-substituted 1,2,3-triazoles, developing a selective and convenient protocol to synthesize N2-aryl-1,2,3-triazoles has been challenging. We report a catalyst-free and regioselective method to access N2-aryl-1,2,3-triazoles in good to excellent yields (66–97%). This scalable postmodification protocol is effective for a wide range of substrates.
Atom economical, safer, scalable, catalyst/additive and solvent free click chemistry using trimethylslilyl azide has been achieved under microwave irradiation.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.
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