59829-81-1Relevant articles and documents
In situ fabricated MOF-cellulose composite as an advanced ROS deactivator-convertor: Fluoroswitchable bi-phasic tweezers for free chlorine detoxification and size-exclusive catalytic insertion of aqueous H2O2
Bankar, Balasaheb D.,Biradar, Ankush V.,Goswami, Ranadip,Neogi, Subhadip,Pillai, Renjith S.,Rajput, Sonal,Seal, Nilanjan
, p. 4316 - 4332 (2022/03/07)
Combining the merits of structural diversity, and purposeful implantation of task-specific functionalities, metal-organic frameworks (MOFs) instigate targeted reactive oxygen species (ROS) scavenging and concurrent detoxification via self-calibrated emission modulation. Then again, grafting of catalytically active sites in MOFs can benefit developing a greener protocol to convert ROS generators to technologically important building blocks, wherein tailorable MOF-composite fabrication is highly sought for practical applications, yet unexplored. The chemo-robust and hydrogen-bonded framework encompassing free -NH2 moiety affixed pores serves as an ultra-fast and highly regenerable fluoro-probe for selective detection of toxic ROS producers hypochlorite ion (ClO-) and H2O2 with record-level nanomolar sensitivity. While the bio-relevant antioxidant l-ascorbic acid (AA) imparts notable quenching to the MOF, a significant 3.5 fold emission enhancement with bi-phasic colorimetric variation ensues when it selectively scavenges ClO- from uni-directional porous channels through an unprecedented molecular tweezer approach. Apart from a battery of experimental evidence, density functional theory (DFT) results validate "on-off-on"fluoroswitching from redistribution of MOF orbital energy levels, and show guest-mediated exclusive transition from "Tight state"to "Loose state". The coordination frustrated metal site engineered pore-wall benefits the dual-functionalized MOF in converting the potential ROS generator H2O2via selective alkene epoxidation under mild-conditions. Importantly, sterically encumbered substrates exhibit poor conversion and demonstrate first-ever pore-fitting-induced size selectivity for this benign oxidation. Judiciously planned control experiments in combination with DFT-optimized intermediates provide proof-of-concept to the ionic route of ROS conversion. Considering an effective way to broaden the advanced applications of this crystalline material, reconfigurable MOF@cotton fiber (CF) is fabricated via in situ growth, which scavenges free chlorine and concomitantly squeezes it upon exposure to AA with obvious colorimetric changes over multiple real-life platforms. Furthermore, multi-cyclic alkene epoxidation by MOF@CF paves the way to futuristic continuous flow reactors that truly serves this smart composite as a bimodal ROS deactivator-convertor and explicitly denotes it as an advanced promising analogue from contemporary state-of-the-art materials.
Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Mycobacterium Species
Khan, Saniya S.,Sudasinghe, Thanuja D.,Landgraf, Alexander D.,Ronning, Donald R.,Sucheck, Steven J.
, (2021/09/27)
Tetrahydrolipstatin (THL, 1a) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several Mycobacterium tuberculosis hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allows modification of the THL α-chain substituent to afford compounds 1a through 1e. The key transformation in the synthesis was use of a (TPP)CrCl/Co2(CO)8-catalyzed regioselective and stereospecific carbonylation on an advanced epoxide intermediate to yield a trans-β-lactone. These compounds are modest inhibitors of Ag85A and Ag85C, two α/β hydrolases of M. tuberculosis involved in the biosynthesis of the mycomembrane. Among these compounds, 10d showed the highest inhibitory effect on Ag85A (34 ± 22 μM) and Ag85C (66 ± 8 μM), and its X-ray structure was solved in complex with Ag85C to 2.5 ? resolution. In contrast, compound 1e exhibited the best-in-class MICs of 50 μM (25 μg/mL) and 16 μM (8.4 μg/mL) against M. smegmatis and M. tuberculosis H37Ra, respectively, using a microtiter assay plate. Combination of 1e with 13 well-established antibiotics synergistically enhanced the potency of few of these antibiotics in M. smegmatis and M. tuberculosis H37Ra. Compound 1e applied at concentrations 4-fold lower than its MIC enhanced the MIC of the synergistic antibiotic by 2-256-fold. In addition to observing synergy with first-line drugs, rifamycin and isoniazid, the MIC of vancomycin against M. tuberculosis H37Ra was 65 μg/mL; however, the MIC was lowered to 0.25 μg/mL in the presence of 2.1 μg/mL 1e demonstrating the potential of targeting mycobacterial hydrolases involved in mycomembrane and peptidoglycan biosynthesis.
Regiocontrolled syntheses of FAHFAs and LC-MS/MS differentiation of regioisomers
Balas, Laurence,Bertrand-Michel, Justine,Viars, Fanny,Faugere, Julien,Lefort, Corinne,Caspar-Bauguil, Sylvie,Langin, Dominique,Durand, Thierry
supporting information, p. 9012 - 9020 (2016/10/07)
An efficient regiospecific total synthesis of several branched fatty acyl hydroxyl-fatty acids (FAHFA) has been achieved from available terminal alkenes and alkynes. The key steps feature a boron trifluoride mediated epoxide ring opening with acetylide carbanions, followed by hydrogenation of the alkyne function. The carboxylic acid of the hydroxylated chains is introduced at the last step of the synthesis to allow the esterification of the branched hydroxyl group by fatty acids beforehand. The chemical syntheses of a "linear" FAHFA and a branched FAHFA analog containing a Z-olefin in the hydroxyl-fatty acid chain are also reported. A LC-MS/MS method has been developed. Several reversed phase columns were compared. Regioisomers were separated.
