An Ultrafast Sonochemical Strategy to Synthesize Lipase‐Manganese Phosphate Hybrid Nanoflowers with Promoted Biocatalytic Performance in the Kinetic Resolution of β‐Aryloxyalcohols

Abstract

Herein we report an expeditious and facile sonochemical synthesis method that takes just a few minutes to produce organic‐inorganic hybrid nanoflowers and their application as a nanobiocatalyst. Surfactant treated Burkholderia cepacia lipase was used as the organic component and manganese sulfate as the inorganic component to synthesize the nanoflowers in less than 10 minutes. Careful investigation of the process parameters was performed to obtain the optimized value for each attribute viz. sonication time (7.5 min), lipase concentration (0.1 mg/mL), MnSO4 concentration (150 mM), sonication frequency (33 kHz) and pH (8.0). An additional post‐synthesis treatment of nanoflowers with N‐hydroxysuccinimide (NHS) increased their reusability to over nine cycles with an overall six‐fold increase in the activity. In addition, thermal stability was demonstrated through a twenty‐fold increase in the half‐life of immobilized lipase at 80 °C than in free form. The hybrid nanoflowers displayed a marked improvement in the kinetic resolution of racemic intermediates of metoprolol, a selective β‐1 blocker drug [C (%)=46.7, eep=96.5, E=156] and cloranolol, a non‐selective β‐blocker drug [C (%)=49.5, eep=96.0, E=157] compared to free lipase which signifies its importance as a nanobiocatalyst.

Immobilization of transaminase from Bacillus licheniformis on copper phosphate nanoflowers and its potential application in the kinetic resolution of RS-α-methyl benzyl amine

“…The reusability can be improved by adding some stabilizer during nanoflower synthesis which is known to reduce leaching of enzymes and also by the careful washings of reaction mixture during recycling. These results are in consistent with previous studies carried out by other researchers in which they immobilized different enzymes for the kinetic resolution of the racemic mixture (Rai et al 2018;Soni et al 2018;Dwivedee et al 2018).…”

“…The time of ultrasonic treatment greatly influences the appropriate formation of nanoflower and encapsulation of enzyme (Soni et al 2018 ). Here we studied the effect of sonication time (5, 10, 15, 20, 25 and 30 min) on NFs synthesis by sonicating the reaction mixture of phosphate-buffer saline (pH 7.4) containing 0.25 mg/mL enzyme with 20 µL CuSO 4 .5H 2 O (120 mM), in a bath sonicator.…”

Biocatalysis: A smart and green tool for the preparation of chiral drugs

“…Because of their stability, bioprocessing efficiency, and downstream recovery, NBCs represent a class of promising nanomaterials that embrace enormous applications in the pharmaceutical industry. Recently, the Burkholderia cepacia lipase was efficiently immobilized in a new hybrid NFs that displayed a marked improvement in the kinetic resolution of racemic intermediates of two β‐blocker drugs (i.e., metoprolol and cloranolol), as outlined in Scheme 5a 74 . Finally, an innovative approach that use dual‐enzyme@CaHPO 4 hybrid nanoflowers (hNFs) was recently utilized to efficiently catalyze the synthesis of the chiral compound ( S )‐1‐(2,6‐dichloro‐3‐fluorophenyl) ethyl alcohol 19 , an important intermediate of the anti‐cancer crizotinib (Scheme 5b).…”

“…Recently, the Burkholderia cepacia lipase was efficiently immobilized in a new hybrid NFs that displayed a marked improvement in the kinetic resolution of racemic intermediates of two β‐blocker drugs (i.e., metoprolol and cloranolol), as outlined in Scheme 5a . 74 Finally, an innovative approach that use dual‐enzyme@CaHPO 4 hybrid nanoflowers (hNFs) was recently utilized to efficiently catalyze the synthesis of the chiral compound ( S )‐1‐(2,6‐dichloro‐3‐fluorophenyl) ethyl alcohol 19 , an important intermediate of the anti‐cancer crizotinib (Scheme 5b ). 75 Furthermore, the use of this innovative nanosupport improves enzymatic activity, thermal stability, and recycling cycles of synthetic reaction (up to 16) and may be applicable also in multi‐enzyme systems.…”

Current Status and Future Perspectives of Supports and Protocols for Enzyme Immobilization

“…It is noteworthy that the increase in the enzyme's thermal stability is usually one of the limiting factors for using free enzymes in high-impact industrial processes [249,254,255]. In addition to this aspect, there is usually an increase in enzyme tolerance by various reactional media, such as organic solvents, and also the primary foundation of immobilization facilitated reuse of the biocatalyst in several reactions cycles [247,248,250].…”