Nuno M. T. Lourenço

Synthesis and properties of tetra-alkyl-dimethylguanidinium salts as a potential new generation of ionic liquids

New room temperature ionic liquids based on the tetra-alkyl-dimethylguanidinium cation present high stability under thermal, basic, acid, nucleophilic and oxidative conditions, low temperature glass transition phases and peculiar solubility properties in common solvents.

A comparative study of biocatalysis in non-conventional solvents: Ionic liquids, supercritical fluids and organic media

The catalytic activities of cutinase immobilized on zeolite NaY and Candida antarctica lipase B immobilized on an acrylic resin (Novozym 453) were measured in a model transesterification reaction in three imidazolium cation-based ionic liquids (RTILs), supercritical ethane (sc-ethane), sc-CO2 and n-hexane, at a water activity (aW) of 0.2 and 0.7. The transesterification activity of cutinase was highest and similar in 1-n-butyl-3-methylimidazolium hexafluorophosphate ([C4mim][PF6]), sc-ethane and n-hexane, more than one order of magnitude lower in sc-CO2, and increased with an increase in aW. Hydrolysis was not detected in sc-fluids and n-hexane, and was observed in RTILs at aW 0.7 only. Both initial rates of transesterification and of hydrolysis of Novozym decreased with an increase in aW. sc-CO2 did not have a deleterious effect on Novozym activity, which was as high as in sc-ethane and n-hexane. The low reaction rates obtained in this case in RTILs suggested the existence of internal diffusion limitations absent in the cutinase preparation where the enzyme is only adsorbed at the surface of the support. sc-CO2 did not adversely affect the catalytic activity of cutinase suspended in [C4mim][PF6], suggesting a protective effect of the RTIL. In the case of Novozym, a marked increase in the rate of transesterification was obtained in the [C4mim][PF6]/sc-CO2 system, compared to the RTIL alone. This may reflect improved mass transfer of solutes to the pores of the immobilization matrix due to a high concentration of dissolved CO2 and a reduction in viscosity of the RTIL.

Simple transformation of crystalline chiral natural anions to liquid medium and their use to induce chirality

New chiral ionic liquids can be prepared simply by combining the tetra-n-hexyl-dimethylguanidinium cation with readily available chiral anions and used as an asymmetric inducing agent as demonstrated for catalytic Rh(II) carbenoid C-H insertion and Sharpless dihydroxylation.

Ionic liquid as an efficient promoting medium for two-phase nucleophilic displacement reactions

Abstract The use of the room temperature ionic liquid (RTIL) 1- n -butyl-3-methylimidazolium hexafluorophosphate as an efficient catalyst and solvent for several representative nucleophilic substitution reactions under aqueous-RTIL phase transfer conditions was explored. Recycling and reuse of the reaction medium was demonstrated for the azide formation.

Efficient catalyst reuse by simple dissolution in non-conventional media

This feature article is a description of the achievements made on the development of attractive sustainable approaches to synthetic organic chemistry, namely, catalyst reuse by simple dissolution in water and ionic liquids and asymmetric transformations induced by readily available chiral ionic liquids.

Lipase catalysed mono and di-acylation of secondary alcohols with succinic anhydride in organic media and ionic liquids

The acylation of the model substrate (R,S)-2-octanol with succinic anhydride catalysed by immobilised Candida antarcticalipase B was studied in two water-miscible organic solvents, two water-immiscible ones, nine 1-alkyl-3-methylimidazolium ionic liquids (RTILs) and two quaternary ammonium RTILs. From previous reports, the reaction was expected to yield an acidic half ester (hemiester). However, it was found that the diester was also produced, in many cases at an even higher yield. The major reaction products were the (R)-hemiester and the (R,R)-diester. In some of the solvents, the amount of hemiester formed increased and then remained constant, whereas in others the amount of hemiester first peaked and then decayed. This behaviour could be explained by the coupling of two reaction pathways: the hydrolysis of the hemiester, and the esterification of the hemiester. The solubility limit of succinic acid, produced in the former pathway, was found to be a discriminating parameter, the precipitation of the acid acting as a driving force for the consumption of the hemiester formed. The impact of the choice of solvent on the outcome of the acylation with succinic anhydride was confirmed by conducting the reaction on a preparative scale: in acetonitrile, the reaction produced 32% (w/w) of (R)-hemiester and 68% (w/w) of (R,R)-diester, whereas in tetrahydrofuran 85% (w/w) of (R)-hemiester and 15% (w/w) of (R,R)-diester were obtained.

Enzymatic resolution of Indinavir precursor in ionic liquids with reuse of biocatalyst and media by product sublimation

Efficient enzymatic resolution of (±)-cis-benzyl N-(1-hydroxyindan-2-yl)carbamate in [aliq][N(CN)2] by acylation using CALB as a biocatalyst was achieved, with the possibility of catalyst and medium reuse. The reaction proceeds to the formation of the corresponding acetate in moderate yield and high enantiomeric excess for the first and second cycles. Additionally, the biocatalyst can be recovered by filtration and reaction products can be easily removed from the ionic liquid by direct sublimation under high vacuum.

Synthesis of choline sulfonate buffers and their effect on cytochrome c dissolution and oxidation state

Seven choline sulfonates with buffering properties were prepared in good yields (74–94%) and high purity by reacting choline hydroxide with different Goods buffers. Choline sulfonate buffers containing hydroxyl group-rich cations appeared to be liquid at room temperature. The dissolution of cytochrome c in the synthesized choline sulfonates was investigated. It was found that complete solubilisation of this heme protein in most of the choline sulfonate buffers can be obtained through addition of 21–31% (w/w%) water. In these hydrated choline sulfonates, cyt c is solubilised in its reduced form.

Protein stabilization with a dipeptide-mimic triazine-scaffolded synthetic affinity ligand

Protein stabilization was achieved by a novel approach based on the adsorption and establishment of affinity‐like interactions with a biomimetic triazine‐scaffolded ligand. A synthetic lead compound (ligand 3′/11, Ka ≈ 104 M−1) was selected from a previously screened solid‐phase library of affinity ligands for studies of adsorption and stabilization of cutinase from Fusarium solani pisi used as a model system. This ligand, directly synthesized in agarose by a well‐established solid‐phase synthesis method, was able to strongly bind cutinase and led to impressive half‐lives of more than 8 h at 70 °C, and of approximately 34 h at 60 °C for bound protein (a 25‐ and 57‐fold increase as compared with the free enzyme, respectively). The ligand density in the solid matrix was found to be a determinant parameter for cutinase stabilization. It is conceivable that the highly stabilizing effect observed results from the binding of more than one ligand residue to the enzyme, creating specific macromolecular configurations that lock structural mobility thus improving molecular stability. Copyright

Low-temperature enzymatic hydrolysis resolution in mini-emulsion media

A low-temperature mini-emulsion medium for the enzymatic resolution of 1-phenylethanol is described for the first time. The enzymatic hydrolysis resolution of 1-phenylethyl esters with different chain-lengths in the presence of Candida antarctica lipase B in mini-emulsion media was shown to be significantly controlled by temperature. In this system, the direct effect of temperature on the mini-emulsion size was observed. For the longer 1-phenylethyl ester, 1-phenylethyl dodecanoate, the enzymatic resolution was promoted exclusively at low temperatures. The preparative mini-emulsion enzymatic reaction of 1-phenylethyl dodecanoate at 4 °C afforded the isolation of (R)-phenylethanol with a yield of 36 % with an ee of 99 %. (S)-Phenylethanol was isolated with a 51 % yield with an ee of 79 %.