Candida ionic liquid

In order to broaden the field of biocatalysis in ionic liquids, other enzyme classes have also been screened. Of special interest are oxidoreductases for the enan-tioselective reduction of prochiral ketones [40]. Formate dehydrogenase from Candida boidinii was found to be stable and active in mixtures of [MMIM][MeS04] with buffer (Entry 12) [41]. So far, however, we have not been able to find an alcohol dehydrogenase that is active in the presence of ionic liquids in order to make use of another advantage of ionic liquids that they increase the solubility of hydrophobic compounds in aqueous systems. On addition of 40 % v/v of [MMIM][MeS04] to water, for example, the solubility of acetophenone is increased from 20 mmol to 200 mmol L ... 

The report from Sheldon and co-workers was the second publication demonstrating the potential use of enzymes in ionic liquids and the first one for lipases (Entry 13) [43]. They compared the reactivity of Candida antarctica lipase in ionic liquids such as [BMIM][PFg] and [BMIM][BF4] with that in conventional organic solvents. In all cases the reaction rates were similar for all of the reactions investigated alcoholysis, ammoniolysis, and per hydrolysis. 

Lipases from C. antarctica and P. cepacia showed higher enantioselectivity in the two ionic liquids l-ethyl-3-methylimidazolium tetrafluoroborate and l-butyl-3-methylimidazolium hexafluoroborate than in THE and toluene, in the kinetic resolution of several secondary alcohols [49]. Similarly, with lipases from Pseudomonas species and Alcaligenes species, increased enantioselectivity was observed in the resolution of 1 -phenylethanol in several ionic liquids as compared to methyl tert-butyl ether [50]. Another study has demonstrated that lipase from Candida rugosa is at least 100% more selective in l-butyl-3-methylimidazolium hexafluoroborate and l-octyl-3-nonylimidazolium hexafluorophosphate than in n-hexane, in the resolution of racemic 2-chloro-propanoic acid [51]. 

Aqueous solutions are not suitable solvents for esterifications and transesterifications, and these reactions are carried out in organic solvents of low polarity [9-12]. However, enzymes are surrounded by a hydration shell or bound water that is required for the retention of structure and catalytic activity [13]. Polar hydrophilic solvents such as DMF, DMSO, acetone, and alcohols (log P<0, where P is the partition coefficient between octanol and water) are incompatible and lead to rapid denaturation. Common solvents for esterifications and transesterifications include alkanes (hexane/log P=3.5), aromatics (toluene/2.5, benzene/2), haloalkanes (CHCI3/2, CH2CI2/I.4), and ethers (diisopropyl ether/1.9, terf-butylmethyl ether/ 0.94, diethyl ether/0.85). Exceptionally stable enzymes such as Candida antarctica lipase B (CAL-B) have been used in more polar solvents (tetrahydrofuran/0.49, acetonitrile/—0.33). Room-temperature ionic liquids [14—17] and supercritical fluids [18] are also good media for a wide range of biotransformations. 

More recently, ionic liquids have also been used as additives. Lee and coworkers explain that ionic liquids may ad as a template during the sol-gel process redudng the shrinkage of the matrix by pore filling and behave as a stabilizer to proted Candida rugosa lipases [184]. 

Biocatalysts also operate in ionic liquids [28]. The ones that have been most widely investigated are the lipase family of enzymes. For example, Candida Antarctica lipase B immobilized in [bmim][BF4] or [bmim][PFe] under anhydrous conditions is able to catalyse transesterifications at rates comparable to those observed in other solvents. Certain lipase mediated enantioselective acylations have even resulted in considerable improvements in enantiomeric excesses... 

Biphasic systems consisting of ionic liquids and supercritical CO2 showed dramatic enhancement in the operational stability of both free and immobilized Candida antarctica lipase B (CALB) in the catalyzed kinetic resolution of rac- -phenylethanol with vinyl propionate at 10 MPa and temperatures between 120 and 150°C (Scheme 30) 275). Hydrophobic ionic liquids, [EMIM]Tf2N or [BMIM]Tf2N, were shown to be essential for the stability of the enzyme in the biotransformation. Notwithstanding the extreme conditions, both the free and isolated enzymes were able specifically to catalyze the synthesis of (J )-l-phenylethyl propionate. The maximum enantiomeric excess needed for satisfactory product purity (ee >99.9%) was maintained. The (S)-l-phenylethanol reactant was not esterified. The authors suggested that the ionic liquids provide protection against enzyme denaturation by CO2 and heat. When the free enzyme was used, [EMIM]Tf2N appeared to be the best ionic liquid to protect the enzyme, which... 

Although [BMIM]BF4 has been evaluated as an isolation medium for lipase-catalyzed biotransformations, the general experience with it has not been favorable, relative to that with other ionic liquids, such as [BMIM]PF6. However, excellent performance was recently reported for [BDMIM]BF4 when it was used to host Candida antarctica (Novozym 435) for the enantioselective transesterification of 5-phenyl-l-penten-3-ol (+ and -) with vinyl acetate. The working hypothesis was that the oligomerization of acetaldehyde may be caused by the C2 proton of the [BMIM] ion because of the unfavorable acidity of this group (226). In contrast, the cation in [BDMIM]BF4 lacks this acidity. 

Since then, the process has been extended to a wide variety of lactones of different size and to several lipases, as recently reviewed [93-96]. Interestingly, large-membered lactones, which are very difficult to polymerize by usual anionic and coordination polymerizations due to the low ring strain, are successfully polymerized by enzymes. Among the different lipases available, that fi om Candida antarctica (lipase CA, CALB or Novozym 435) is the most widely used due to its high activity. An alcohol can purposely be added to the reaction medium to initiate the polymerization instead of water. The polymerization can be carried out in bulk, in organic solvents, in water, and in ionic liquids. Interestingly, Kobayashi and coworkers reported in 2001 the ROP of lactones by lipase CA in supercritical CO2... 

De Diego, T., Lozano, R, Gmouh, S., Vaultier, M., Iborra, J.L., Understanding structure-stability relationships of Candida antartica lipase B in ionic liquids, Biomacromol., 6,1457-1464, 2005. 

The cutinase from Fusarium solani pisii maintained its transesterification activity in [BMIm][BF4], [OMIm][PF6] and [BMIm][PF6] (in order of increasing activity) at aw=0.2 [59]. Candida rugosa lipase (CrL), which is generally much less tolerant of anhydrous media than other microbial lipases, has successfully been used in anhydrous as well as water-saturated ionic liquids [60, 61, 62, 63, 64, 65]. 

F. J., Janssen, M.H.A., Schoevaart, R., van Rantwijk, F. and Sheldon, R.A. (2007) Cross-linked Candida antarctica lipase B is active in denaturing ionic liquids. Enz. Microb. Technol., 40, 1095. 

In the last few years increasing attention has been devoted to conducting bio-catalytic transformations in ionic liquids [104-107]. The first report of enzyme-(lipase-) catalyzed reactions in water-free ionic liquids dates from 2000 and involved transesterification, ammoniolysis and perhydrolysis reactions catalyzed by Candida antarctica lipase B (Fig. 7.32) [108]. 

Lou, W.-Y., Zong, M.-H., Liu, Y.-Y., and Wang, J.-F. 2006. Efficient enantioselective hydrolysis of D,L-phenylglycine methyl ester catalyzed by immobilized Candida antarctica lipase B in ionic liquid containing systems. Journal of Biotechnology, 125 64—74. 

The activity of microorganisms in organic solvents has been observed to have useful applications in the synthesis of organic materials. Using an ionic liquid solvent system of ionic liquid and water, Cull and coworkers have reported the a two-phase biotransformation with cells of Rhodococcus R312 [3]. Extensive research of Candida antarctica-cat lyzed reactions has also been carried out for catalyzing alcoholysis, ammoniolysis, and perhydrolysis reactions in ionic liquids ([bmim][BF4] or [bmimllPFe]), Scheme 10.1. 

In addition, Itoh and coworkers have reported that acylation of the alcohol was accomplished by three types of enzymes Candida Antarctica lipase (CAL, Novozym 435), lipase QL Alcalgenes sp.), and lipase PS Pseudomonas cepacia). Scheme 10.5. The desired acetate showed extremely high enantioselectivity, but no reaction took place when lipase (CRL, Candida rugosa) or Procine liver lipase (PPL) was used as the catalyst in the ionic liquid (Table 10.3). 

Immobilized lipase B from Candida antarctica (CALB) (Novozym 435) was obtained from Novo Nordisk Novozymes. All chemicals and ionic liquids used were of the highest available purity. 

Habulin M, Knez Z (2009) Optimization of (R, S)-l-phenylethanol kinetic resolution over Candida antarctica lipase B in ionic liquids. J Mol Catal B Enzym 58 24-28... 

Even though CaLB is the lipase most widely used in ionic liquids, other lipases such as Pseudomonas cepacia lipase (PcL) and Candida rugosa lipase (CrL) have been often used as biocatalyst for ester synthesis in ionic liquid [13, 14]. Nara et al. 

The application of ionic liquids in lipase biocatalysis has not remained entirely restricted to CaLB, PcL or CrL. Other lipases have been used in ionic liquids for ester synthesis such as Candida antarctica lipase A (CaLA) [15,16], Thermomyces lanuginosus lipase [17] (TLL), Rhizomucor miehei lipase (PmL), Pseudomonas fluorescens lipase (PJL) [18], Pig pancreas lipase (PpL) [17] and Alcaligenes sp. lipase (A5 L) [16]. 

Ruiz A, de los Rios AP, Herndndez FJ, Janssen MHA, Schoevaart R, van Rantwijk F, Sheldon RA (2007) A cross-linked enzyme aggregate of Candida antarvtica Upase B is active in denaturing ionic liquids. Enzyme Microb Technol 40 1095-1099... 

Lozano P, Piamtongkam R, Kohns K, de Diego T, Vaultier M, Iborra JL (2007) Ionic liquids improve dtroneUyl ester synthesis catalyzed by immobilized Candida antarctica lipase B in solvent-free media. Green Chem 9 780-784... 

Lau RM, Sorgedrager MJ, Carrea G, van Rantwijk F (2004) Dissolution of Candida antarctica lipase B in ionic liquids effects on structure and activity. Green Chem 6 483 87... 

Noel M, Lozano P, Vaultier M, Iborra JL (2004) Kinetic resolution of rac-2-pentanol catalyzed by Candida antarctica lipase B in the ionic liquid, l-butyl-3-methyUmidazolium bis[(trifluoromethyl)sulfonyl]amide. Biotechnol Lett 26 301-306... 

Ulbert O, Frdter T, Belafi-Bako K, Gubicza L (2004) Enhanced enantioselectivity of Candida rugosa lipase in ionic liquids as compared to organic solvents. J Mol Catal B Enzym 31 39 5... 

Fig. 8.1 Experimental set-up of the recirculating enzymatic membrane reactor used for the synthesis of butyl propionate from vinyl propionate and 1-butanol catalysed by Candida antarctica lipase B in supercritical carbon dioxide and supercritical carbon dioxide/ionic liquid biphasic system [17]...

Fig. 8.4 Initial reaction rate (bars) and selectivity (points) exhibited by free Candida antarctica lipase B for butyl propionate synthesis in supercritical carbon dioxide and in four different ionic liquids/supercritical carbon dioxide systems. The reaction conditions were r=50°C, vinyl propionate 150 mM and 1-butanol 100 Mm [38]...

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