Aqueous Micellar Media Research Articles

Lipase-catalyzed esterification in water enabled by nanomicelles. Applications to 1-pot multi-step sequences.

Esterification in an aqueous micellar medium is catalyzed by a commercially available lipase in the absence of any co-factors. The presence of only 2 wt% designer surfactant, TPGS-750-M, assists in a 100% selective enzymatic process in which only primary alcohols participate (in a 1 : 1 ratio with carboxylic acid). An unexpected finding is also disclosed where the simple additive, PhCF3 (1 equiv. vs. substrate), appears to significantly extend the scope of usable acid/alcohol combinations. Taken together, several chemo- and bio-catalyzed 1-pot, multi-step reactions can now be performed in water.

Determination of the activation parameters ∆H≠ and ∆S≠ via a kinetic study of d,l-mandelic acid oxidation by using chromic acid in the presence of 1,10-phenanthroline as a promoter in an aqueous micellar acid medium

Chromic acid oxidation of d,l-mandelic acid in the presence and absence of 1,10-phenanthroline (Phen) is studied in an aqueous micellar medium under kinetic conditions, [d,l-mandelic acid] >> [Phen]T >> [Cr(VI)]T at different temperatures. From studies on the effect of temperature on the rate constant (k), the activation parameters ∆H≠ (enthalpy of activation) and ∆S≠ (entropy of activation) are evaluated by using the Eyring equation [−ln (kh/kBT) = ∆H≠/RT − ∆S≠/R]. The high value of ∆H≠ indicates that the phen-catalysed path is favoured mainly due to very high negative value of ∆S≠. The negative value of ∆S≠ and the composite rate constant kcat support the suggested cyclic transition state. Both the catalysed and uncatalysed paths show a first-order dependence on [H+], and both also show a first-order dependence on [d,l-mandelic acid]T and [Cr(VI)]T. The Phen-catalysed path is first order in [Phen]T. These observations remain unaltered in the presence of externally added surfactants. The cationic surfactant N-cetylpyridinium chloride is found to retard the rate of the reaction.

Synthesis and screening for antioxidant and cytotoxic activities of novel 2-thioxo-benzo[f]chromeno[2,3-d]pyrimidin-4-ones derived by cetylpyridinium chloride catalyzed multicomponent reactions in aqueous micellar media

The cetylpyridinium chloride (CPC) has been used as micellar catalyst in three-component one-pot reaction involving thiobarbituric acids, aromatic aldehydes and β-napthol for synthesizing the novel 2-thioxo-benzo[5,6]chromeno[2,3-d]pyrimidin-4-one derivatives in aqueous media. These 2-thioxo-benzo[5,6]chromeno[2,3-d]pyrimidin-4-one derivatives have been screened for antioxidant and cytotoxic activities. It has been found that 2-thioxo-5-(4-nitrophenyl)-benzo[f]chromeno[2,3-d]pyrimidin-4-one (4a) has shown highest scavenging activity value to reduce DPPH free radicals, which may be due to the presence of nitro group at para-position. Three compounds, 4a, 4b and 4o show significant in vitro antitumor activity. The study of the antioxidant and cytotoxic activities reveal that all the compounds show moderate to good activity indicating that the presence of thiouriedo linkage in the pyrimidine nucleus and the chromeno group attached to pyrimidene moiety are responsible for these activities.

Rhodamine B phenylhydrazide as a new chemosensor for sulfite quantification: Application to food samples

A simple and sensitive spectrophotometric method for the quantification of sulfite at trace level has been proposed. The method is based on the change in the intensity of the color developed on reaction of sulfite with Rhodamine-B Phenyl hydrazide (RBPH) in aqueous micellar medium. The experimental conditions such as pH, concentration of RBPH and Tween 80 have been optimized and calibration plot has been constructed. The proposed method offers a wide linearity in the concentration range 0–15 ppm of sulfite. The limit of detection and limit of quantification were found to be 0.006 and 1.5 ppm respectively, with the regression co-efficient R2 = 0.992. The proposed method has been successfully applied to measure the trace level sulfite in food samples such as tomato ketchup, jam, dry grapes, sugar and wine. Comparison of the developed method with standard protocol showed good recoveries.

Copper-Catalyzed Asymmetric Reductions of Aryl/Heteroaryl Ketones under Mild Aqueous Micellar Conditions.

Enantioselective syntheses of nonracemic secondary alcohols have been achieved in an aqueous micellar medium via copper-catalyzed (Cu(OAc)2·H2O/(R)-3,4,5-MeO-MeO-BIPHEP) reduction of aryl/heteroaryl ketones. This methodology serves as a green protocol to access enantio-enriched alcohols under mild conditions (0-22 °C) using a base metal catalyst, together with an inexpensive, innocuous, and convenient stoichiometric hydride source (PMHS). The secondary alcohol products are formed in good to excellent yields with ee values greater than 90%.

Kinetics of oxidation of antidiabetic drug metformin hydrochloride by vanadium(V) in acidic and micellar medium

The kinetics of oxidation of antidiabetic drug metformin by vanadium(V) have been studied spectrophotometrically under pseudo-first order conditions in aqueous acidic and micellar medium. The observed rate of oxidation is first order with respect to both metformin and H+. The pseudo-first order rate constant is independent of ionic strength and varies inversely with dielectric constant of the medium. The effect of micelles (SDS and TX 100) on such reactions has been investigated. Sodiumdodecyl sulphate (SDS) and iso-octylphenoxy polyethoxyether (TX100) accelerate the rate of electron transfer reaction except for cationic CTAB due to the cloudiness of the reaction mixture. It is a one electron transfer process where vanadium(V)is reduced to vanadium(IV) supported by cyclic voltammetric study. The main oxidation product was identified as metformin N-oxide by FTIR and LCMS method. Activation parameters of such reaction have been calculated and reaction mechanism is suggested. Computational study based on Hartree–Fock method supports the reaction mechanism.

Sustainable Synthetic Approaches for 3‐Aminoimidazo‐fused Heterocycles via Groebke‐Blackburn‐Bienaymé Process

AbstractTwo different sustainable and efficient synthetic methods have been developed for the synthesis of a variety of 3‐aminoimidazo fused heterocycles by one‐pot three component reaction of 2‐aminoazines, aldehydes and isocyanides. The methods adopted were (a) aqueous micellar mediated condition (method A) (b) VB1 catalyzed reaction under solvent‐free condition (method B). Excellent yields were obtained for a broad range of biologically significant imidazopyridine core molecules under green conditions at room temperature. Synthesis in aqueous micellar medium, mild reaction conditions, organocatalyst, easy work‐up and isolation, and gram scale synthesis, are some of the advantages of these protocols.

Targeted Ultrasound Contrast Imaging of Tumor Vasculature With Positively Charged Microbubbles.

Molecular ultrasound imaging of tumor vasculature is being actively investigated with microbubble contrast agents targeted to neovasculature biomarkers. Yet, a universal method of targeting tumor vasculature independent of specific biomarkers, or in their absence, would be desirable. We report the use of electrostatic interaction to achieve adherence of microbubbles to tumor vasculature and resulting tumor delineation by ultrasound imaging. Microbubbles were prepared from decafluorobutane gas by amalgamation of aqueous micellar medium. Distearoyl phosphatidylcholine (DSPC) and polyethylene glycol (PEG)-stearate were used as microbubble shell-forming lipids; cationic lipid distearoyl trimethylammoniumpropane (DSTAP) was included to introduce positive electrostatic charge. Microbubbles were subjected to flotation in normal gravity, to remove larger particles. Murine colon adenocarcinoma tumor (MC38, J. Schlom, National Institutes of Health) was inoculated in the hind leg of C57BL/6 mice. Contrast ultrasound imaging was performed under isoflurane anesthesia, using a clinical imaging system in low power mode, with tissue signal suppression (contrast pulse sequencing, 7 MHz, 1 Hz; Mechanical Index, 0.2). The ultrasound probe was positioned to monitor the tumor and contralateral leg muscle; microbubble contrast signal was monitored for 30 minutes or more, after intravenous bolus administration of 2.10 microbubbles. Individual time point frames were extracted from ultrasound video recording and analyzed with ImageJ. Mean bubble diameter was ~1.6 to 2 μm; 99.9% were less than 5 μm, to prevent blocking blood flow in capillaries. For cationic DSTAP-carrying microbubbles, contrast signal was observed in the tumor beyond 30 minutes after injection. As the fraction of positively charged lipid in the bubble shell was increased, adherent contrast signal in the tumor also increased, but accumulation of DSTAP-microbubbles in the normal muscle increased as well. For bubbles with the highest positive charge tested, DSTAP-DSPC molar ratio 1:4, at 10 minutes after intravenous administration of microbubbles, the contrast signal difference between the tumor and normal muscle was 1.5 (P < 0.005). At 30 minutes, tumor/muscle contrast signal ratio improved and reached 2.1. For the DSTAP-DSPC 1:13 preparation, tumor/muscle signal ratio exceeded 3.6 at 10 minutes and reached 5.4 at 30 minutes. Microbubbles with DSTAP-DSPC ratio 1:22 were optimal for tumor targeting: at 10 minutes, tumor/muscle signal ratio was greater than 7 (P < 0.005); at 30 minutes, greater than 16 (P < 0.01), sufficient for tumor delineation. Cationic microbubbles are easy to prepare. They selectively accumulate in the tumor vasculature after intravenous administration. These microbubbles provide target-to-control contrast ratio that can exceed an order of magnitude. Adherent microbubbles delineate the tumor mass at extended time points, at 30 minutes and beyond. This may allow for an extension of the contrast ultrasound examination time. Overall, positively charged microbubbles could become a universal ultrasound contrast agent for cancer imaging.

Sustainable Palladium-Catalyzed Tsuji-Trost Reactions Enabled by Aqueous Micellar Catalysis.

Palladium-catalyzed allylic substitution, or "Tsuji-Trost" reactions, can be run under micellar catalysis conditions featuring not only chemistry in water but also numerous combinations of reaction partners that require low levels of palladium, typically on the order of 1000 ppm (0.1 mol %). These couplings are further characterized by especially mild conditions, leading to a number of cases not previously reported in an aqueous micellar medium. Inclusion of diverse nucleophiles, such as N-H heterocycles, alcohols, dicarbonyl compounds, and sulfonamides is described. Intramolecular cyclizations further illustrate the broad utility of this process. In addition to recycling studies, a multigram scale example is reported, indicative of the prospects for scale up.

Aerobic α‐Sulfonylation of Ketones with Zinc Sulfinates in Aqueous Micellar Media: Highly Selective Access to β‐Keto Sulfones

AbstractAn efficient, inexpensive and environmentally friendly synthesis of β‐ketosulfones, via NaI‐catalyzed oxidative sulfonylation of ketones with zinc sulfinates, employing ethylene dibromide (EDB) and air as the oxidants, is described. EDB was shown to be a mild organic oxidant to convert NaI into molecular iodine that promote the cross‐coupling reactions of zinc sulfinates with ketones, producing β‐ketosulfones. Mechanistic studies indicated that a radical pathway might be involved in the reaction process. The key feature of the present protocol is the far greater solubility of NaI and sulfinates in micellar arrays present in aqueous solution where the oxidative coupling reactions are taking place.

Composition, stability and fluorescence properties of metal complexes of an aza-flavonol analog 1-methyl-2-phenyl-3-hydroxy-4(1H)-quinolone in aqueous solution

Aza-flavonols are compounds containing the 3-hydroxy-4(1H)-quinolone moiety, a unique scaffold with applications expanding from fluorescent probes and bioimaging to potential metal-related pharmaceutical drugs. Compositions and stability constants of metal complexes of an aza-flavonol 1-methyl-2-phenyl-3-hydroxy-4(1H)-quinolone (LH) in aqueous micellar medium of hexadecyltrimethylammonium bromide were established by fluorescence and spectrophotometric titrations of LH in the presence of metal ions of different type at variable pH. Strong binding with quenching of ligand fluorescence was observed for Cu2+, Fe2+/3+ and Pb2+ cations. The complexation with Zn2+ induced strong fluorescence enhancement in ZnL+ complex and smaller enhancement in ZnL2 complex. Al3+, Ga3+ and Me2Sn2+ cations induced strong fluorescence enhancement in 1:1 ML complexes, but quenching in ML2 complexes. Together with the relevant literature data these results indicate that the quenching effect in 1:2 complexes along with strong fluorescence enhancement in respective 1:1 complexes is a general phenomenon for 3-hydroxypyranone and 3-hydroxypyridinone ligands. The quantum mechanical Natural Transition Orbital analysis of ground and excited states of LH, AlL2+ and AlL2+ species reveals that the fluorescence of AlL2+ complex is quenched by an internal electron transfer process, which is absent in the 1:1 AlL2+ complex. The results emphasize strong dependence of the coordination induced fluorescence changes on the complex composition.

N2Phos - an easily made, highly effective ligand designed for ppm level Pd-catalyzed Suzuki-Miyaura cross couplings in water.

A new biaryl phosphine-containing ligand from an active palladium catalyst for ppm level Suzuki–Miyaura couplings, enabled by an aqueous micellar reaction medium. A wide array of functionalized substrates including aryl/heteroaryl bromides are amenable, as are, notably, chlorides. The catalytic system is both general and highly effective at low palladium loadings (1000–2500 ppm or 0.10–0.25 mol%). Density functional theory calculations suggest that greater steric congestion in N2Phos induces increased steric crowding around the Pd center, helping to destabilize the 2 : 1 ligand–Pd(0) complex more for N2Phos than for EvanPhos (and less bulky ligands), and thereby favoring formation of the 1 : 1 ligand–Pdo complex that is more reactive in oxidative addition to aryl chlorides.

Photo-Fries rearrangement in flow under aqueous micellar conditions.

A flow edition of photo-Fries rearrangement for the synthesis of 2-acylphenols in an aqueous micellar medium has been described. We take advantage of a narrow channel reactor and micelle-induced confinement effect to refine both the efficiency and selectivity of the parent photoreaction.

A Kinetic Investigation of Metal-Dipeptide Complex with Ninhydrin in the Absence and Presence of CTAB Micelles.

This paper presents the results of a kinetic study performed between ninhydrin and a Ni(II) dipeptide complex under various conditions. The rate of formation of the imine adduct was measured spectrophotometrically both in plain aqueous media and in aqueous micellar media in which CTAB (cetyltrimethylammonium bromide) is used as the surfactant. These studies were carried out at pH 5 and over a temperature a range of 50 to 70°C. Studies were also conducted to elucidate the effect of some organic sodium salts on the rate of this reaction. In these studies, it was found that the formation of imine adduct followed a first-order kinetics with respect to [Ni(II)-Gly-Leu]+ in both aqueous and micellar medium. A fractional-order kinetics was observed with respect to ninhydrin, again in both aqueous and micellar media. Increase in the total concentration of CTAB from 0 to 40×10-3 mol dm-3 resulted in approximately two folds increase in the pseudo-first-order rate constant (kψ). The rate constant (kΨ) in micellar medium first increased with increase in CTAB concentration, reached a maximum value, and finally, with further increase in CTAB concentration, a decreasing effect was observed. Quantitative kinetic analysis of kψ-[CTAB] data was performed on the basis of the pseudo-phase model of the micelles. The rate profile in presence of CTAB suggests a cooperative effect in the enhanced formation of the imine adduct as is commonly found in enzyme catalyzed reactions. Addition of organic sodium salts (such as benzoate, salicylate and tosylate) enhanced the rate at lower concentrations but rates start to decrease at higher concentrations. This suggests that tightly binding organic counter-anions were the most effective. Viscosity of the reaction media seems to affect the kinetic behavior in micellar media.

Fe-Catalyzed Reductive Couplings of Terminal (Hetero)Aryl Alkenes and Alkyl Halides under Aqueous Micellar Conditions.

The combination of a vinyl-substituted aromatic or heteroaromatic and an alkyl bromide or iodide leads, in the presence of Zn and a catalytic amount of an Fe(II) salt, to a net reductive coupling. The new C-C bond is regiospecifically formed at rt at the β-site of the alkene. The coupling only occurs in an aqueous micellar medium, where a radical process is likely, supported by several control experiments. A mechanism based on these data is proposed.

Micelle-Enabled One-Pot Guanidine Synthesis in Water Directly from Isothiocyanate using Hypervalent Iodine(III) Reagents under Mild Conditions.

In this work, we developed a one-pot synthesis of guanidine directly from isothiocyanate using DIB (diacetoxyiodobenzene) as a desulfurizing agent under micellar conditions in water. Our optimization study revealed that the use of 1 % TPGS-750-M as a surfactant with NaOH as an additive base at room temperature can convert a variety of isothiocyanates and amines into corresponding guanidines in excellent yields (69-95 %). This synthetic process in water can be applied to prepare guanidine at gram-scale quantity. Our aqueous micellar medium also demonstrated high reusability as the reaction can be performed for several cycles without losing its efficiency. The reaction is metal-free, utilizes water as solvent and practical (room temperature and open flask).

Micellar catalysed oxidation of hydrophobic fatty alcohol in aqueous medium

Oxidation of a hydrophobic fatty alcohol was carried out under pseudo 1st order reaction condition in aqueous micellar medium efficiently. In addition to the dissolution of alcohol micelles are found to catalyse the oxidation reaction. Use of promoters further enhanced the rate of the reaction with almost instant completion of the reaction via the formation of active oxidants (AO+). The product was confirmed by IR and NMR study. Fluorescence studies and DLS measurements were done to confirm the formation of AO+. NMR studies were carried out to establish the interaction between the surfactants and 1-Octanol. Calculated activation parameters (ΔH≠, ΔS≠) also support the experimental findings.

Synthesis of 2-(Prop-2-ynyloxy) Benzaldehyde using Salicyl Aldehyde and Propargyl Bromide in Aqueous Micellar Media

Abstract Advances in science and technology are promoting eco-friendly synthesis routes, green chemicals, and non-hazardous solvents. A suitable method for the synthesis of 2-(prop-2-ynyloxy) benzaldehyde was developed using three different aqueous micellar media. The targeted product ether is completely immiscible in water, but in combination with interface active surfactants it has been possible to produce the hydrophobic organic compound in water. Micelles function as a pseudocellular organic environment to isolate species from the main solvent and favor compartmentalization of reagents. There is an increase in the local concentration and consequently the reactivity increases. The use of such unique chemo-, regio-, and stereoselectivity renders this reaction new. Organic species added to a micellar media are distributed between water and micelles depending on polarity, charge, and size. In the experiments it was observed that salicylaldehyde and propargyl bromide interacted best in CTAB media and the yield of the formed product was 96 %.

Chemiluminescence of naphthalene analogues of luminol in solution and micellar media

The chemiluminescence of several naphthalene-based luminol analogues is characterized and compared with that of luminol. The compounds produce a strong greenish or green-yellow chemiluminescence in alkaline aqueous and nonaqueous solutions by reaction with hydrogen peroxide in the presence of hexacyanoferrate (III). The results point to the possibility of increasing the sensitivity of analytical methods currently based on luminol. The photophysics of the oxidation products is also studied. The solubility of some of the new compounds in aqueous solution is significantly increased using a nonionic surfactant Triton X-100. Increase of the chemiluminescence intensity in aqueous micellar media was observed. The location of the oxidation product 3-aminophthalate in the external hydrophilic shell of the micelle was established using its intrinsic fluorescence by iodide. The described luminol analogues may prove of interest in forensic and other applications.

Efficient and "Green" Synthetic Route to Imidazo[1,2-a]pyridine by Cu(II)-Ascorbate-Catalyzed A3-Coupling in Aqueous Micellar Media.

An efficient and environmentally sustainable method for the synthesis of imidazo[1,2-a]pyridine derivatives by domino A3-coupling reaction catalyzed by Cu(II)–ascorbate was developed in aqueous micellar media in the presence of sodium dodecyl sulfate (SDS). The catalyst, a dynamic combination of Cu(II)/Cu(I), was generated in situ in the reaction mixture by mixing CuSO4 with sodium ascorbate and aided a facile 5-exo-dig cycloisomerization of alkynes with the condensation products of 2-aminopyridines and aldehydes to afford a variety of imidazo[1,2-a]pyridines in good overall yields. A simple experimental setup, water as the “green” medium, and inexpensive catalyst and auxiliary are some of the merits of this protocol.