Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations
The effects of the reaction medium and substrate concentration were studied on the selectivity of Novozym 435 using the asymmetric hydrolysis of dimethyl-3-phenylglutarate as a model reaction. Results show that the use of choline chloride ChCl:urea/phosphate buffer 50% (<i>v/v</i>) as a...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/4/792 |
| _version_ | 1830414418007031808 |
|---|---|
| author | Yerko Fredes Lesly Chamorro Zaida Cabrera |
| author_facet | Yerko Fredes Lesly Chamorro Zaida Cabrera |
| author_sort | Yerko Fredes |
| collection | DOAJ |
| description | The effects of the reaction medium and substrate concentration were studied on the selectivity of Novozym 435 using the asymmetric hydrolysis of dimethyl-3-phenylglutarate as a model reaction. Results show that the use of choline chloride ChCl:urea/phosphate buffer 50% (<i>v/v</i>) as a reaction medium increased the selectivity of Novozym 435 by 16% (e.e = 88%) with respect to the one in 100% phosphate buffer (e.e = 76%). Best results were obtained when high substrate concentrations (well above the solubility limit, 27-fold) and ChCl:urea/phosphate buffer 50% (<i>v/v</i>) as reaction medium at pH 7 and 30 °C were used. Under such conditions, the <i>R</i>-monoester was produced with an enantiomeric purity of 99%. Novozym 435 was more stable in ChCl:urea/phosphate buffer 50% (<i>v/v</i>) than in phosphate buffer, retaining a 50% of its initial activity after 27 h of incubation at pH 7 and 40 °C. Results suggest that the use of deep eutectic solvents (ChCl:urea/phosphate buffer) in an heterogeneous reaction system (high substrate concentration) is a viable and promising strategy for the synthesis of chiral drugs from highly hydrophobic substrates. |
| first_indexed | 2024-12-20T20:44:43Z |
| format | Article |
| id | doaj.art-476eb5c20dc94c11a315d62c4033e7a4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T20:44:43Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-476eb5c20dc94c11a315d62c4033e7a42022-12-21T19:27:05ZengMDPI AGMolecules1420-30492019-02-0124479210.3390/molecules24040792molecules24040792Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate ConcentrationsYerko Fredes0Lesly Chamorro1Zaida Cabrera2School of Biochemical Engineering, Pontificia Universidad Católica de Valparaíso; Avda. Brasil 2085 Valparaíso, ChileSchool of Biochemical Engineering, Pontificia Universidad Católica de Valparaíso; Avda. Brasil 2085 Valparaíso, ChileSchool of Biochemical Engineering, Pontificia Universidad Católica de Valparaíso; Avda. Brasil 2085 Valparaíso, ChileThe effects of the reaction medium and substrate concentration were studied on the selectivity of Novozym 435 using the asymmetric hydrolysis of dimethyl-3-phenylglutarate as a model reaction. Results show that the use of choline chloride ChCl:urea/phosphate buffer 50% (<i>v/v</i>) as a reaction medium increased the selectivity of Novozym 435 by 16% (e.e = 88%) with respect to the one in 100% phosphate buffer (e.e = 76%). Best results were obtained when high substrate concentrations (well above the solubility limit, 27-fold) and ChCl:urea/phosphate buffer 50% (<i>v/v</i>) as reaction medium at pH 7 and 30 °C were used. Under such conditions, the <i>R</i>-monoester was produced with an enantiomeric purity of 99%. Novozym 435 was more stable in ChCl:urea/phosphate buffer 50% (<i>v/v</i>) than in phosphate buffer, retaining a 50% of its initial activity after 27 h of incubation at pH 7 and 40 °C. Results suggest that the use of deep eutectic solvents (ChCl:urea/phosphate buffer) in an heterogeneous reaction system (high substrate concentration) is a viable and promising strategy for the synthesis of chiral drugs from highly hydrophobic substrates.https://www.mdpi.com/1420-3049/24/4/792asymmetric synthesisNovozym 435deep eutectic solventsdimethyl-3-phenylglutaratehydrophobic substrates |
| spellingShingle | Yerko Fredes Lesly Chamorro Zaida Cabrera Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations Molecules asymmetric synthesis Novozym 435 deep eutectic solvents dimethyl-3-phenylglutarate hydrophobic substrates |
| title | Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations |
| title_full | Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations |
| title_fullStr | Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations |
| title_full_unstemmed | Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations |
| title_short | Increased Selectivity of Novozym 435 in the Asymmetric Hydrolysis of a Substrate with High Hydrophobicity Through the Use of Deep Eutectic Solvents and High Substrate Concentrations |
| title_sort | increased selectivity of novozym 435 in the asymmetric hydrolysis of a substrate with high hydrophobicity through the use of deep eutectic solvents and high substrate concentrations |
| topic | asymmetric synthesis Novozym 435 deep eutectic solvents dimethyl-3-phenylglutarate hydrophobic substrates |
| url | https://www.mdpi.com/1420-3049/24/4/792 |
| work_keys_str_mv | AT yerkofredes increasedselectivityofnovozym435intheasymmetrichydrolysisofasubstratewithhighhydrophobicitythroughtheuseofdeepeutecticsolventsandhighsubstrateconcentrations AT leslychamorro increasedselectivityofnovozym435intheasymmetrichydrolysisofasubstratewithhighhydrophobicitythroughtheuseofdeepeutecticsolventsandhighsubstrateconcentrations AT zaidacabrera increasedselectivityofnovozym435intheasymmetrichydrolysisofasubstratewithhighhydrophobicitythroughtheuseofdeepeutecticsolventsandhighsubstrateconcentrations |