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Hua Zhao

University of Minnesota - Twin Cities, Department of bioproducts and biosystems engineering, Faculty Member

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My research interests include biocatalysis in ionic liquids, DNA-based asymmetric catalysis, biofuels (cellulosic ethanol and biodiesel), and the synthesis of active pharmaceutical ingredients (APIs). My research group website: https://sites.google.com/site/huazhao98/

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Papers by Hua Zhao

New eutectic ionic liquids for lipase activation and enzymatic preparation of biodiesel

Organic & Biomolecular Chemistry, 2011

The enzymatic preparation of biodiesel has been hampered by the lack of suitable solvents with de... more The enzymatic preparation of biodiesel has been hampered by the lack of suitable solvents with desirable properties such as high lipase compatibility, low cost, low viscosity, high biodegradability, and ease of product separation. Recent interest in using ionic liquids (ILs) as advanced reaction media has led to fast reaction rates and high yields in the enzymatic synthesis of biodiesel. However, conventional (i.e., cation-anion paired) ILs based on imidazolium and other quaternary ammonium salts remain too expensive for wide application at industrial scales. In this study, we report on newly-synthesized eutectic ILs derived from choline acetate or choline chloride coupled with biocompatible hydrogen-bond donors, such as glycerol. These eutectic solvents have favorable properties including low viscosity, high biodegradability, and excellent compatibility with Novozym® 435, a commercial immobilized Candida antarctica lipase B. Furthermore, in a model biodiesel synthesis system, we demonstrate high reaction rates for the enzymatic transesterification of Miglyol® oil 812 with methanol, catalyzed by Novozym® 435 in choline acetate/glycerol (1 : 1.5 molar ratio). The high conversion (97%) of the triglyceride obtained within 3 h, under optimal conditions, suggests that these novel eutectic solvents warrant further exploration as potential media in the enzymatic production of biodiesel. Recently, the Abbott group 10-12 has demonstrated that the mixture of a solid organic salt and a suitable complexing agent can sometimes liquify at temperatures below 100 °C, a socalled 'deep eutectic IL'. The mechanism put forth is that the complexing agent (typically a hydrogen-bond donor) interacts with the anion, thereby increasing its effective size and shielding its interaction with the cation, in turn inducing a depression in the melting point (T m) of the mixture. A superb example is the mixture of choline chloride (T m = 302 °C, 2-† Electronic supplementary information (ESI) available. See

Aqueous ionic liquids and deep eutectic solvents for cellulosic biomass pretreatment and saccharification

RSC Advances, 2014

Runge-Kutta algorithm To curve-fit our hydrolysis data using the Michaelis-Menten equation (Eq. 1... more Runge-Kutta algorithm To curve-fit our hydrolysis data using the Michaelis-Menten equation (Eq. 1), the Runge-Kutta algorithm was followed to make four evaluations of d[S]/dt between each time step. The first evaluation is the same as the Euler's method. The second and third use the previous step to evaluate d[S]/dt at the middle of the time step, and the fourth evaluation uses the third at the end of the time step. The four evaluations are weighted and used to generate a single step from i to i+1. The equations are: k 1 = t d[S i ]/dt k 2 = t d([S i ] + k 1 /2)/dt k 3 = t d([S i ] + k 2 /2)/dt k 4 = t d([S i ] + k 3)/dt [S i+1 ] = [S i ] + k 1 /6 + k 2 /3+ k 3 /3 +k 4 /6 Values of V max and K m can be calculated from the above equations using Excel Solver through minimizing the SSE value (sum of the squares of the error), which is defined below as the sum of

Enzymatic ring-opening polymerization (ROP) of polylactones: roles of non-aqueous solvents

Journal of Chemical Technology & Biotechnology, 2017

Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, renewa... more Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, renewable and biocompatible polymers with high potentials to replace petrochemical based synthetic polymers. A benign route for synthesizing these polyesters is through the enzymecatalyzed ring-opening polymerization (ROP) reaction; this type of enzymatic process is very sensitive to reaction conditions such as solvents, water content and temperature. This review systematically discusses the crucial roles of different solvents (such as solvent-free or in bulk, organic solvents, supercritical fluids, ionic liquids, and aqueous biphasic systems) on the degree of polymerization and polydispersity. In general, many studies suggest that hydrophobic organic solvents with minimum water contents lead to efficient enzymatic polymerization and subsequently high molecular weights of polyesters; the selection of solvents is also limited by the reaction temperature, e.g. the ROP of lactide is often conducted at above 100 °C, therefore, the solvent typically needs to have its boiling point above this temperature. The use of supercritical fluids could be limited by its scaling-up potential, while ionic liquids have exhibited many advantages include their low-volatility, high thermal stability, controllable enzyme-compatibility, and a wide range of choices. However, the fundamental and mechanistic understanding of the specific roles of ionic liquids in enzymatic ROP reactions is still lacking. Furthermore, the lipase specificity towards Land D-lactide is also surveyed, followed by the discussion of engineered lipases with improved enantioselectivity and thermal stability. In addition, the preparation of polyester-derived materials such as polyester-grafted cellulose by the enzymatic ROP method is briefly reviewed.

DNA-Based Asymmetric Catalysis: Role of Ionic Solvents and Glymes

RSC advances, 2014

Recently, DNA has been evaluated as a chiral scaffold for metal complexes to construct so called ... more Recently, DNA has been evaluated as a chiral scaffold for metal complexes to construct so called 'DNA-based hybrid catalysts', a robust and inexpensive alternative to enzymes. The unique chiral structure of DNA allows the hybrid catalysts to catalyze various asymmetric synthesis reactions. However, most current studies used aqueous buffers as solvents for these asymmetric reactions, where substrates/products are typically suspended in the solutions. The mass transfer limitation usually requires a long reaction time. To overcome this hurdle and to advance DNA-based asymmetric catalysis, we evaluated a series of ionic liquids (ILs), inorganic salts, deep eutectic solvents (DES), glymes, glycols, acetonitrile and methanol as co-solvents/additives for the DNA-based asymmetric Michael addition. In general, these additives induce indistinguishable changes to the DNA B-form duplex conformation as suggested by circular dichroism (CD) spectroscopy, but impose a significant influence ...

ChemInform Abstract: Glymes as Versatile Solvents for Chemical Reactions and Processes: From the Laboratory to Industry

ChemInform, 2014

PEG-functionalized ionic liquids for cellulose dissolution and saccharification

Green Chemistry, 2012

diyl)bis(triethylammonium-N-yl) diacetate (1, [TEG-(Et 3 N) 2 ][OAc] 2). 1 H-NMR (400 MHz, CDCl 3... more diyl)bis(triethylammonium-N-yl) diacetate (1, [TEG-(Et 3 N) 2 ][OAc] 2). 1 H-NMR (400 MHz, CDCl 3 , [ppm]) δ = 1.34 (18H, t, 2×(CH 3 CH 2) 3 N, J = 6.0 Hz), 1.87 (6H, s, 2×CH 3 COO-), 3.50 (12H, m, 2×(CH 3 CH 2) 3 N), 3.62 (4H, m, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N), 3.68-3.72 (4H, m, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N), 3.96 (2H, t, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N,

Characterizing the binding of nucleotide ATP on serum albumin by 31 P NMR diffusion

Canadian Journal of Chemistry, 2012

The pulsed-field-gradient (PFG) 31P NMR diffusion spectra were measured under varied sample condi... more The pulsed-field-gradient (PFG) 31P NMR diffusion spectra were measured under varied sample conditions to characterize the low-affinity binding of adenosine 5′-triphosphate (ATP) on human serum albumin (HSA) or bovine serum albumin (BSA). The NMR diffusion constants of ATP, ATP–HSA, or ATP–BSA were illustrated as function of ATP concentrations. The binding curves of ATP–HSA and ATP–BSA were identical but strikingly different from the ATP curve. Using a “Scatchard plot”, the apparent binding constant (K) and number of ATP binding sites (n) on serum albumin were evaluated as K = 75.25 (mol/L)–1 and n = 10, respectively. At a pH < 5.0 and a pH > 9.0 or a temperature > 45 °C, the diffusion data of ATP–HSA were found to increase remarkably, suggesting that the dissociation of ATP from HSA was largely enhanced, probably because of pH- or heat-induced protein structural change, degradation, or aggregation. In addition, our data indicated that ADP was strongly competitive with ATP ...

Glymes as benign co-solvents for CaO-catalyzed transesterification of soybean oil to biodiesel

Bioresource Technology, 2013

h i g h l i g h t s Glymes were found to reduce the saponification reaction during biodiesel prep... more h i g h l i g h t s Glymes were found to reduce the saponification reaction during biodiesel preparation. Glymes are benign solvents with low toxicity and volatility. Glymes are miscible with triglycerides including soybean oil. SEM suggests a dissolutionagglomeration process of CaO surface in glyme. A 99% stoichiometric conversion of soybean oil was achieved in glymes in 4 h. g r a p h i c a l a b s t r a c t Glyme as co-solvent is capable of activating CaO to be an effective catalyst for the fast conversion of soybean oil to biodiesel.

New ionic derivatives of betulinic acid as highly potent anti-cancer agents

Bioorganic & Medicinal Chemistry Letters, 2012

Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. Ho... more Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC 50 value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC 50 value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.

Migration of reactive trace compounds from Novozym® 435 into organic solvents and ionic liquids

Biochemical Engineering Journal, 2010

The commercial form of immobilized Candida antarctica lipase B (CALB), known as Novozym ® 435, is... more The commercial form of immobilized Candida antarctica lipase B (CALB), known as Novozym ® 435, is a catalyst routinely used in enzymatic reactions. However, we observed a number of compounds migrated from this enzyme preparation into organic solvents and ionic liquids (ILs). These compounds were further identified by GC-MS analysis as a mixture of 17 substances, including 5 major components: glycerol, benzoic acid, 2-hydroxyethyl benzoate, 2-hydroxyethyl sorbate, and sorbic acid. The importance of this discovery is that all five major compounds are reactive in the presence of CALB, especially the last four compounds are potential acyl donors in enzymatic (trans)esterification reactions. We then quantified the migration of these acyl donors into various aqueous solutions, organic solvents and ILs, and observed that the migration into polar organic solvents and ILs was rapid (10-30 min). We also measured the reactivities of these acyl donors with 1-propanol in Novozym ® 435-catalyzed (trans)esterifications. Our data suggest that the initial reaction rates of sorbic acid and sorbate ester were very fast; although the initial rates of benzoic acid and benzoate were much slower, their conversions into propyl benzoate were significant within 24 h period. The presence of these compounds in Novozym ® 435 may not have considerable impact on fast reactions involving high substrate concentrations, however, it is important to realize that these trace compounds may affect the enzyme activity, and may cause confusion during the analysis of enzymatic reactions.

New Ether-Functionalized Ionic Liquids for Lipase-Catalyzed Synthesis of Biodiesel

Applied Biochemistry and Biotechnology, 2009

Ionic liquids (ILs) are being explored as solvents for the enzymatic methanolysis of triglyceride... more Ionic liquids (ILs) are being explored as solvents for the enzymatic methanolysis of triglycerides. However, most available ILs (especially hydrophobic ones) have poor capability in dissolving lipids, while hydrophilic ILs tend to cause enzyme inactivation. Recently, we synthesized a new type of ether-functionalized ionic liquids (ILs) carrying anions of acetate or formate; they are capable of dissolving a variety of substrates and are also lipase-compatible (Green Chem., 2008, 10, 696-705). In the present study, we carried out the lipase-catalyzed transesterifications of Miglyol® oil 812 and soybean oil in these novel ILs. These ILs are capable of dissolving oils at the reaction temperature (50°C); meanwhile, lipases maintained high catalytic activities in these media even in high concentrations of methanol (up to 50% v/v). High conversions of Miglyol oil were observed in mixtures of IL and methanol (70/30, v/v) when the reaction was catalyzed by a variety of lipases and different enzyme preparations (free and immobilized), especially with the use of two alkylammonium ILs 2 and 3. The preliminary study on the transesterification of soybean oil in IL/methanol mixtures further confirms the potential of using oil-dissolving and lipase-stabilizing ILs in the efficient production of biodiesels.

Determining Nucleotide Acidity and Cation Binding Constants by 31P NMR

Can. J. Anal. Sci. …, 2008

Page 1. Canadian Journal of Analytical Sciences and Spectroscopy Determining nucleotide acidity a... more

DNA stability in ionic liquids and deep eutectic solvents

Journal of Chemical Technology & Biotechnology, 2014

DNA molecules are known as the genetic information carriers. Recently, they are being explored as... more DNA molecules are known as the genetic information carriers. Recently, they are being explored as a new generation of biocatalysts or chiral scaffolds for metal catalysts. There is also a growing interest of finding alternative solvents for DNA preservation and stabilization, including two unique types of solvents: ionic liquids (ILs) and deep eutectic solvents (DES). Therefore, it is important to understand how DNA molecules interact with these novel ionic solvent systems (i.e. ILs and DES). It is well known that inorganic di-and monovalent ions preferentially bind with major and minor grooves of DNA structures. However, in the case of ILs and DES, organic cation may intrude into the DNA minor grooves; more importantly, electrostatic attraction between organic cations and the DNA phosphate backbone becomes a predominant interaction, accompanying by hydrophobic and polar interactions between ILs and DNA major and minor grooves. In addition, anions may form hydrogen-bonds with cytosine, adenine and guanine bases. Despites these strong interactions, DNA molecules maintain double helical structure in most ionic solvent systems, especially in aqueous IL solutions. Furthermore, the exciting advances of Gquadruplexe DNA structures in ILs and DES are discussed.

Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012

Betulinic acid is a natural product possessing abundant and favourable biological activity, inclu... more Betulinic acid is a natural product possessing abundant and favourable biological activity, including anti-cancer, anti-malarial, anti-inflammatory and anti-HIV properties, while causing minimal toxicity to unaffected cells. The full biological potency of betulinic acid cannot be fully unlocked, however, for a number of reasons, a primary one being its limited solubility in aqueous and biologically pertinent organic media. Aiming to improve the water solubility of betulinic acid without disrupting its structurally related bioactivity, we have prepared different ionic derivatives of betulinic acid. Inhibition bioassays on HIV-1 protease-catalysed peptide hydrolysis indicate significantly improved performance resulting from converting the betulinic acid to organic salt form. Indeed, for one particular cholinium-based derivative, its water solubility is improved more than 100 times and the half maximal inhibitory concentration (IC 50) value (22 μg mL −1) was onethird that of wide-type betulinic acid (60 μg mL −1). These encouraging results advise that additional studies of ionic betulinic acid derivatives as a therapeutic solution against HIV-1 infection are warranted.

Enzymatic ring-opening polymerization (ROP) of lactides and lactone in ionic liquids and organic solvents: digging the controlling factors

RSC Adv.

Certain organic solvents and ionic liquids could promote the enzymatic ring-opening polymerizatio... more

Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

RSC Advances

New glycol-functionalized ionic liquids exhibit high thermal stability and are lipase-compatible,... more

Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

RSC Advances

New glycol-functionalized ionic liquids exhibit high thermal stability and are lipase-compatible,... more

“Water-like” Dual-Functionalized Ionic Liquids for Enzyme Activation

ACS Omega

By mimicking the water structure to improve the enzyme activity, we designed imidazolium (Im)-bas... more By mimicking the water structure to improve the enzyme activity, we designed imidazolium (Im)-based ionic liquids (ILs) functionalized with both ether and tert-alcohol groups (e.g., [CH 3 (OCH 2 CH 2 ) n -Im-t-BuOH][Tf 2 N]). This unique combination of the "water-like" structure enabled very high transesterification (synthetic) activities for immobilized lipase B from Candida antarctica, which are up to 2−4 folds higher than nonfunctionalized "classical" ionic liquids (such as [BMIM][Tf 2 N]) and up to 40−100% higher than diisopropyl ether and tert-butanol. Fluorescence emission spectra confirmed the general protein structural preservation in these tailored ionic solvents. In addition, functionalized ILs showed high thermal stabilities, which are comparable with diisopropyl ether but much higher than tert-butanol. Article http://pubs.acs.org/journal/acsodf Cite This: ACS Omega XXXX, XXX, XXX−XXX

Chiral synthesis and enzymatic resolution of S-(−)-piperazine-2-carboxylic acid using enzyme alcalase

Enantiomer A Journal of Stereochemistry

Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic resolution of m... more

Deep eutectic solvents: sustainable media for nanoscale and functional materials

Accounts of chemical research, Jan 19, 2014

Deep eutectic solvents (DESs) represent an alternative class of ionic fluids closely resembling r... more Deep eutectic solvents (DESs) represent an alternative class of ionic fluids closely resembling room-temperature ionic liquids (RTILs), although, strictly speaking, they are distinguished by the fact that they also contain an organic molecular component (typically, a hydrogen bond donor like a urea, amide, acid, or polyol), frequently as the predominant constituent. Practically speaking, DESs are attractive alternatives to RTILs, sharing most of their remarkable qualities (e.g., tolerance to humidity, negligible vapor pressure, thermostability, wide electrochemical potential windows, tunability) while overcoming several limitations associated with their RTIL cousins. Particularly, DESs are typically, less expensive, more synthetically accessible (typically, from bulk commodity chemicals using solvent/waste-free processes), nontoxic, and biodegradable. In this Account, we provide an overview of DESs as designer solvents to create well-defined nanomaterials including shape-controlled ...

New eutectic ionic liquids for lipase activation and enzymatic preparation of biodiesel

Organic & Biomolecular Chemistry, 2011

The enzymatic preparation of biodiesel has been hampered by the lack of suitable solvents with de... more The enzymatic preparation of biodiesel has been hampered by the lack of suitable solvents with desirable properties such as high lipase compatibility, low cost, low viscosity, high biodegradability, and ease of product separation. Recent interest in using ionic liquids (ILs) as advanced reaction media has led to fast reaction rates and high yields in the enzymatic synthesis of biodiesel. However, conventional (i.e., cation-anion paired) ILs based on imidazolium and other quaternary ammonium salts remain too expensive for wide application at industrial scales. In this study, we report on newly-synthesized eutectic ILs derived from choline acetate or choline chloride coupled with biocompatible hydrogen-bond donors, such as glycerol. These eutectic solvents have favorable properties including low viscosity, high biodegradability, and excellent compatibility with Novozym® 435, a commercial immobilized Candida antarctica lipase B. Furthermore, in a model biodiesel synthesis system, we demonstrate high reaction rates for the enzymatic transesterification of Miglyol® oil 812 with methanol, catalyzed by Novozym® 435 in choline acetate/glycerol (1 : 1.5 molar ratio). The high conversion (97%) of the triglyceride obtained within 3 h, under optimal conditions, suggests that these novel eutectic solvents warrant further exploration as potential media in the enzymatic production of biodiesel. Recently, the Abbott group 10-12 has demonstrated that the mixture of a solid organic salt and a suitable complexing agent can sometimes liquify at temperatures below 100 °C, a socalled 'deep eutectic IL'. The mechanism put forth is that the complexing agent (typically a hydrogen-bond donor) interacts with the anion, thereby increasing its effective size and shielding its interaction with the cation, in turn inducing a depression in the melting point (T m) of the mixture. A superb example is the mixture of choline chloride (T m = 302 °C, 2-† Electronic supplementary information (ESI) available. See

Aqueous ionic liquids and deep eutectic solvents for cellulosic biomass pretreatment and saccharification

RSC Advances, 2014

Runge-Kutta algorithm To curve-fit our hydrolysis data using the Michaelis-Menten equation (Eq. 1... more Runge-Kutta algorithm To curve-fit our hydrolysis data using the Michaelis-Menten equation (Eq. 1), the Runge-Kutta algorithm was followed to make four evaluations of d[S]/dt between each time step. The first evaluation is the same as the Euler's method. The second and third use the previous step to evaluate d[S]/dt at the middle of the time step, and the fourth evaluation uses the third at the end of the time step. The four evaluations are weighted and used to generate a single step from i to i+1. The equations are: k 1 = t d[S i ]/dt k 2 = t d([S i ] + k 1 /2)/dt k 3 = t d([S i ] + k 2 /2)/dt k 4 = t d([S i ] + k 3)/dt [S i+1 ] = [S i ] + k 1 /6 + k 2 /3+ k 3 /3 +k 4 /6 Values of V max and K m can be calculated from the above equations using Excel Solver through minimizing the SSE value (sum of the squares of the error), which is defined below as the sum of

Enzymatic ring-opening polymerization (ROP) of polylactones: roles of non-aqueous solvents

Journal of Chemical Technology & Biotechnology, 2017

Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, renewa... more Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, renewable and biocompatible polymers with high potentials to replace petrochemical based synthetic polymers. A benign route for synthesizing these polyesters is through the enzymecatalyzed ring-opening polymerization (ROP) reaction; this type of enzymatic process is very sensitive to reaction conditions such as solvents, water content and temperature. This review systematically discusses the crucial roles of different solvents (such as solvent-free or in bulk, organic solvents, supercritical fluids, ionic liquids, and aqueous biphasic systems) on the degree of polymerization and polydispersity. In general, many studies suggest that hydrophobic organic solvents with minimum water contents lead to efficient enzymatic polymerization and subsequently high molecular weights of polyesters; the selection of solvents is also limited by the reaction temperature, e.g. the ROP of lactide is often conducted at above 100 °C, therefore, the solvent typically needs to have its boiling point above this temperature. The use of supercritical fluids could be limited by its scaling-up potential, while ionic liquids have exhibited many advantages include their low-volatility, high thermal stability, controllable enzyme-compatibility, and a wide range of choices. However, the fundamental and mechanistic understanding of the specific roles of ionic liquids in enzymatic ROP reactions is still lacking. Furthermore, the lipase specificity towards Land D-lactide is also surveyed, followed by the discussion of engineered lipases with improved enantioselectivity and thermal stability. In addition, the preparation of polyester-derived materials such as polyester-grafted cellulose by the enzymatic ROP method is briefly reviewed.

DNA-Based Asymmetric Catalysis: Role of Ionic Solvents and Glymes

RSC advances, 2014

Recently, DNA has been evaluated as a chiral scaffold for metal complexes to construct so called ... more Recently, DNA has been evaluated as a chiral scaffold for metal complexes to construct so called 'DNA-based hybrid catalysts', a robust and inexpensive alternative to enzymes. The unique chiral structure of DNA allows the hybrid catalysts to catalyze various asymmetric synthesis reactions. However, most current studies used aqueous buffers as solvents for these asymmetric reactions, where substrates/products are typically suspended in the solutions. The mass transfer limitation usually requires a long reaction time. To overcome this hurdle and to advance DNA-based asymmetric catalysis, we evaluated a series of ionic liquids (ILs), inorganic salts, deep eutectic solvents (DES), glymes, glycols, acetonitrile and methanol as co-solvents/additives for the DNA-based asymmetric Michael addition. In general, these additives induce indistinguishable changes to the DNA B-form duplex conformation as suggested by circular dichroism (CD) spectroscopy, but impose a significant influence ...

ChemInform Abstract: Glymes as Versatile Solvents for Chemical Reactions and Processes: From the Laboratory to Industry

ChemInform, 2014

PEG-functionalized ionic liquids for cellulose dissolution and saccharification

Green Chemistry, 2012

diyl)bis(triethylammonium-N-yl) diacetate (1, [TEG-(Et 3 N) 2 ][OAc] 2). 1 H-NMR (400 MHz, CDCl 3... more diyl)bis(triethylammonium-N-yl) diacetate (1, [TEG-(Et 3 N) 2 ][OAc] 2). 1 H-NMR (400 MHz, CDCl 3 , [ppm]) δ = 1.34 (18H, t, 2×(CH 3 CH 2) 3 N, J = 6.0 Hz), 1.87 (6H, s, 2×CH 3 COO-), 3.50 (12H, m, 2×(CH 3 CH 2) 3 N), 3.62 (4H, m, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N), 3.68-3.72 (4H, m, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N), 3.96 (2H, t, NCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 N,

Characterizing the binding of nucleotide ATP on serum albumin by 31 P NMR diffusion

Canadian Journal of Chemistry, 2012

The pulsed-field-gradient (PFG) 31P NMR diffusion spectra were measured under varied sample condi... more The pulsed-field-gradient (PFG) 31P NMR diffusion spectra were measured under varied sample conditions to characterize the low-affinity binding of adenosine 5′-triphosphate (ATP) on human serum albumin (HSA) or bovine serum albumin (BSA). The NMR diffusion constants of ATP, ATP–HSA, or ATP–BSA were illustrated as function of ATP concentrations. The binding curves of ATP–HSA and ATP–BSA were identical but strikingly different from the ATP curve. Using a “Scatchard plot”, the apparent binding constant (K) and number of ATP binding sites (n) on serum albumin were evaluated as K = 75.25 (mol/L)–1 and n = 10, respectively. At a pH < 5.0 and a pH > 9.0 or a temperature > 45 °C, the diffusion data of ATP–HSA were found to increase remarkably, suggesting that the dissociation of ATP from HSA was largely enhanced, probably because of pH- or heat-induced protein structural change, degradation, or aggregation. In addition, our data indicated that ADP was strongly competitive with ATP ...

Glymes as benign co-solvents for CaO-catalyzed transesterification of soybean oil to biodiesel

Bioresource Technology, 2013

h i g h l i g h t s Glymes were found to reduce the saponification reaction during biodiesel prep... more h i g h l i g h t s Glymes were found to reduce the saponification reaction during biodiesel preparation. Glymes are benign solvents with low toxicity and volatility. Glymes are miscible with triglycerides including soybean oil. SEM suggests a dissolutionagglomeration process of CaO surface in glyme. A 99% stoichiometric conversion of soybean oil was achieved in glymes in 4 h. g r a p h i c a l a b s t r a c t Glyme as co-solvent is capable of activating CaO to be an effective catalyst for the fast conversion of soybean oil to biodiesel.

New ionic derivatives of betulinic acid as highly potent anti-cancer agents

Bioorganic & Medicinal Chemistry Letters, 2012

Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. Ho... more Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC 50 value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC 50 value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.

Migration of reactive trace compounds from Novozym® 435 into organic solvents and ionic liquids

Biochemical Engineering Journal, 2010

The commercial form of immobilized Candida antarctica lipase B (CALB), known as Novozym ® 435, is... more The commercial form of immobilized Candida antarctica lipase B (CALB), known as Novozym ® 435, is a catalyst routinely used in enzymatic reactions. However, we observed a number of compounds migrated from this enzyme preparation into organic solvents and ionic liquids (ILs). These compounds were further identified by GC-MS analysis as a mixture of 17 substances, including 5 major components: glycerol, benzoic acid, 2-hydroxyethyl benzoate, 2-hydroxyethyl sorbate, and sorbic acid. The importance of this discovery is that all five major compounds are reactive in the presence of CALB, especially the last four compounds are potential acyl donors in enzymatic (trans)esterification reactions. We then quantified the migration of these acyl donors into various aqueous solutions, organic solvents and ILs, and observed that the migration into polar organic solvents and ILs was rapid (10-30 min). We also measured the reactivities of these acyl donors with 1-propanol in Novozym ® 435-catalyzed (trans)esterifications. Our data suggest that the initial reaction rates of sorbic acid and sorbate ester were very fast; although the initial rates of benzoic acid and benzoate were much slower, their conversions into propyl benzoate were significant within 24 h period. The presence of these compounds in Novozym ® 435 may not have considerable impact on fast reactions involving high substrate concentrations, however, it is important to realize that these trace compounds may affect the enzyme activity, and may cause confusion during the analysis of enzymatic reactions.

New Ether-Functionalized Ionic Liquids for Lipase-Catalyzed Synthesis of Biodiesel

Applied Biochemistry and Biotechnology, 2009

Ionic liquids (ILs) are being explored as solvents for the enzymatic methanolysis of triglyceride... more Ionic liquids (ILs) are being explored as solvents for the enzymatic methanolysis of triglycerides. However, most available ILs (especially hydrophobic ones) have poor capability in dissolving lipids, while hydrophilic ILs tend to cause enzyme inactivation. Recently, we synthesized a new type of ether-functionalized ionic liquids (ILs) carrying anions of acetate or formate; they are capable of dissolving a variety of substrates and are also lipase-compatible (Green Chem., 2008, 10, 696-705). In the present study, we carried out the lipase-catalyzed transesterifications of Miglyol® oil 812 and soybean oil in these novel ILs. These ILs are capable of dissolving oils at the reaction temperature (50°C); meanwhile, lipases maintained high catalytic activities in these media even in high concentrations of methanol (up to 50% v/v). High conversions of Miglyol oil were observed in mixtures of IL and methanol (70/30, v/v) when the reaction was catalyzed by a variety of lipases and different enzyme preparations (free and immobilized), especially with the use of two alkylammonium ILs 2 and 3. The preliminary study on the transesterification of soybean oil in IL/methanol mixtures further confirms the potential of using oil-dissolving and lipase-stabilizing ILs in the efficient production of biodiesels.

Determining Nucleotide Acidity and Cation Binding Constants by 31P NMR

Can. J. Anal. Sci. …, 2008

Page 1. Canadian Journal of Analytical Sciences and Spectroscopy Determining nucleotide acidity a... more

DNA stability in ionic liquids and deep eutectic solvents

Journal of Chemical Technology & Biotechnology, 2014

DNA molecules are known as the genetic information carriers. Recently, they are being explored as... more DNA molecules are known as the genetic information carriers. Recently, they are being explored as a new generation of biocatalysts or chiral scaffolds for metal catalysts. There is also a growing interest of finding alternative solvents for DNA preservation and stabilization, including two unique types of solvents: ionic liquids (ILs) and deep eutectic solvents (DES). Therefore, it is important to understand how DNA molecules interact with these novel ionic solvent systems (i.e. ILs and DES). It is well known that inorganic di-and monovalent ions preferentially bind with major and minor grooves of DNA structures. However, in the case of ILs and DES, organic cation may intrude into the DNA minor grooves; more importantly, electrostatic attraction between organic cations and the DNA phosphate backbone becomes a predominant interaction, accompanying by hydrophobic and polar interactions between ILs and DNA major and minor grooves. In addition, anions may form hydrogen-bonds with cytosine, adenine and guanine bases. Despites these strong interactions, DNA molecules maintain double helical structure in most ionic solvent systems, especially in aqueous IL solutions. Furthermore, the exciting advances of Gquadruplexe DNA structures in ILs and DES are discussed.

Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012

Betulinic acid is a natural product possessing abundant and favourable biological activity, inclu... more Betulinic acid is a natural product possessing abundant and favourable biological activity, including anti-cancer, anti-malarial, anti-inflammatory and anti-HIV properties, while causing minimal toxicity to unaffected cells. The full biological potency of betulinic acid cannot be fully unlocked, however, for a number of reasons, a primary one being its limited solubility in aqueous and biologically pertinent organic media. Aiming to improve the water solubility of betulinic acid without disrupting its structurally related bioactivity, we have prepared different ionic derivatives of betulinic acid. Inhibition bioassays on HIV-1 protease-catalysed peptide hydrolysis indicate significantly improved performance resulting from converting the betulinic acid to organic salt form. Indeed, for one particular cholinium-based derivative, its water solubility is improved more than 100 times and the half maximal inhibitory concentration (IC 50) value (22 μg mL −1) was onethird that of wide-type betulinic acid (60 μg mL −1). These encouraging results advise that additional studies of ionic betulinic acid derivatives as a therapeutic solution against HIV-1 infection are warranted.

Enzymatic ring-opening polymerization (ROP) of lactides and lactone in ionic liquids and organic solvents: digging the controlling factors

RSC Adv.

Certain organic solvents and ionic liquids could promote the enzymatic ring-opening polymerizatio... more

Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

RSC Advances

New glycol-functionalized ionic liquids exhibit high thermal stability and are lipase-compatible,... more

Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

RSC Advances

New glycol-functionalized ionic liquids exhibit high thermal stability and are lipase-compatible,... more

“Water-like” Dual-Functionalized Ionic Liquids for Enzyme Activation

ACS Omega

By mimicking the water structure to improve the enzyme activity, we designed imidazolium (Im)-bas... more By mimicking the water structure to improve the enzyme activity, we designed imidazolium (Im)-based ionic liquids (ILs) functionalized with both ether and tert-alcohol groups (e.g., [CH 3 (OCH 2 CH 2 ) n -Im-t-BuOH][Tf 2 N]). This unique combination of the "water-like" structure enabled very high transesterification (synthetic) activities for immobilized lipase B from Candida antarctica, which are up to 2−4 folds higher than nonfunctionalized "classical" ionic liquids (such as [BMIM][Tf 2 N]) and up to 40−100% higher than diisopropyl ether and tert-butanol. Fluorescence emission spectra confirmed the general protein structural preservation in these tailored ionic solvents. In addition, functionalized ILs showed high thermal stabilities, which are comparable with diisopropyl ether but much higher than tert-butanol. Article http://pubs.acs.org/journal/acsodf Cite This: ACS Omega XXXX, XXX, XXX−XXX

Chiral synthesis and enzymatic resolution of S-(−)-piperazine-2-carboxylic acid using enzyme alcalase

Enantiomer A Journal of Stereochemistry

Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic resolution of m... more

Deep eutectic solvents: sustainable media for nanoscale and functional materials

Accounts of chemical research, Jan 19, 2014

Deep eutectic solvents (DESs) represent an alternative class of ionic fluids closely resembling r... more Deep eutectic solvents (DESs) represent an alternative class of ionic fluids closely resembling room-temperature ionic liquids (RTILs), although, strictly speaking, they are distinguished by the fact that they also contain an organic molecular component (typically, a hydrogen bond donor like a urea, amide, acid, or polyol), frequently as the predominant constituent. Practically speaking, DESs are attractive alternatives to RTILs, sharing most of their remarkable qualities (e.g., tolerance to humidity, negligible vapor pressure, thermostability, wide electrochemical potential windows, tunability) while overcoming several limitations associated with their RTIL cousins. Particularly, DESs are typically, less expensive, more synthetically accessible (typically, from bulk commodity chemicals using solvent/waste-free processes), nontoxic, and biodegradable. In this Account, we provide an overview of DESs as designer solvents to create well-defined nanomaterials including shape-controlled ...