We report a strategy to develop heterogeneous single‐site enantioselective catalysts based on naturally occurring amino acids and earth‐abundant metals for eco‐friendly asymmetric catalysis. The grafting of amino acids within the pores of a metal‐organic framework (MOF), followed by post‐synthetic metalation with iron precursor, affords highly active and enantioselective (>99 % ee for 10 examples) catalysts for hydrosilylation and hydroboration of carbonyl compounds. Impressively, the MOF‐Fe catalyst displayed high turnover numbers of up to 10 000 and was recycled and reused more than 15 times without diminishing the enantioselectivity. MOF‐Fe displayed much higher activity and enantioselectivity than its homogeneous control catalyst, likely due to the formation of robust single‐site catalyst in the MOF through site‐isolation.
Abstract. Self-emulsifying drug delivery system (SEDDS) is the isotropic and thermodynamically stable mixture of oil, surfactant, co-solvent/surfactant, and drug. It emulsifies spontaneously when introduced into an aqueous phase under a mild agitation. The current study was aimed to prepare SNEDDS to augment solubility, release rate, and oral bioavailability of BCS class II drug, efavirenz (EFV). A series of oil, surfactant, and co-surfactant was screened out by a ternary phase diagram to locate a better homogenous mixture. The prepared SNEDDS was evaluated regarding its appearance, mean droplet size, phase separation, in vitro drug release, and oral bioavailability. Among the screened oil, surfactant, and cosurfactant, Labrafil M 2125 CS, Tween 80, and Transcutol®P mixture exhibited superior solubilizing capacity, respectively. Optimized SNEDDS exhibits 98.39% drug release. SNEDDS dissolution behavior was attributed to oil/surfactant ratios and properties of the surfactant phase. It also demonstrates threefold increments in the area under curve (AUC) in comparison to neat EFV. Furthermore, the optimized SNEDDS does not show any vitrification during its 3-month storage. In the present study, better performance of SNEDDS is explained by various factors like (i) improved surface area of droplets, (ii) superior solubilization potential for hydrophobic drugs due to Labrafil M 2125 CS, and (iii) result of surfactant on mucosal permeability. This study demonstrated that SNEDDS may be an alternative approach for the poorly soluble drugs to improve their solubility and oral bioavailability. KEY WORDS: efavirenz; self-nano-emulsifying drug delivery system; ternary phase diagram.
The development of highly efficient and enantioselective heterogeneous catalysts based on earth-abundant elements and inexpensive chiral ligands is essential for environment-friendly and economical production of optically active compounds. We report a strategy of synthesizing chiral amino alcohol-functionalized metal–organic frameworks (MOFs) to afford highly enantioselective single-site base-metal catalysts for asymmetric organic transformations. The chiral MOFs (vol-UiO) were prepared by grafting of chiral amino alcohol such as l-valinol within the pores of aldehyde-functionalized UiO-MOFs via formation of imine linkages. The metalation of vol-UiO with FeCl2 in THF gives amino alcohol coordinated octahedral FeII species of vol-FeCl(THF)3 within the MOFs as determined by X-ray absorption spectroscopy. Upon activation with LiCH2SiMe3, vol-UiO-Fe catalyzed hydrosilylation and hydroboration of a range of aliphatic and aromatic carbonyls to afford the corresponding chiral alcohols with enantiomeric excesses up to 99%. Vol-UiO-Fe catalysts have high turnover numbers of up to 15 000 and could be reused at least 10 times without any loss of activity and enantioselectivity. The spectroscopic, kinetic, and computational studies suggest iron-hydride as the catalytic species, which undergoes enantioselective 1,2-insertion of carbonyl to give an iron-alkoxide intermediate. The subsequent σ-bond metathesis between Fe–O bond and Si–H bond of silane produces chiral silyl ether. This work highlights the importance of MOFs as the tunable molecular material for designing chiral solid catalysts based on inexpensive natural feedstocks such as chiral amino acids and base-metals for asymmetric organic transformations.
We report a highly active single-site heterogeneous cobalt-catalyst based on a porous and robust pyridylimine-functionalized metal–organic frameworks (pyrim-MOF) for chemoselective borylation of arene and benzylic C–H bonds. The pyrim-MOF having UiO-68 topology, constructed from zirconium-cluster secondary building units and pyridylimine-functionalized dicarboxylate bridging linkers, was metalated with CoCl2 followed by treatment of NaEt3BH to give the cobalt-functionalized MOF-catalyst (pyrim-MOF-Co). Pyrim-MOF-Co has a broad substrate scope, allowing the C–H borylation of halogen-, alkoxy-, alkyl-substituted arenes as well as heterocyclic ring systems using B2pin2 or HBpin (pin = pinacolate) as the borylating agent to afford the corresponding arene- or alkyl-boronate esters in good yields. Pyrim-MOF-Co gave a turnover number (TON) of up to 2500 and could be recycled and reused at least 9 times. Pyrim-MOF-Co was also significantly more robust and active than its homogeneous control, highlighting the beneficial effect of active-site isolation within the MOF framework that prevents intermolecular decomposition. The experimental and computational studies suggested (pyrim•−)CoI(THF) as the active catalytic species within the MOF, which undergoes a mechanistic pathway of oxidative addition, turnover limiting σ-bond metathesis, followed by reductive elimination to afford the boronate ester.
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