Influence Of Dimethyl Sulfoxide Research Articles

Ring-opening reaction of aziridines with amines under the influence of dimethyl sulfoxide

The ring-opening reaction of various aziridines with amines proceeded at room temperature to afford the corresponding 1,2-diamines in good to excellent yields using only 3–5equiv dimethyl sulfoxide (DMSO) to aziridines in hexane. This reaction can be performed with easy handling and proceeds under mild reaction conditions. Also a variety of amines are available as a nucleophile.

Macroscopic and microscopic study of 1-ethyl-3-methyl-imidazolium acetate-DMSO mixtures.

Macroscopic (steady-state viscosity, density) and microscopic (NMR chemical shifts, (1)H NMR relaxation times, and diffusion) properties of the 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc])-dimethyl sulfoxide (DMSO) mixture were studied in detail as a function of DMSO molar fraction at various temperatures. Temperature dependencies were used to calculate the activation energies. NMR results indicate that at low molar fraction of DMSO (<0.4), it weakly associates with the cation and in doing so disrupts the strong ion-ion association that exists in the pure ionic liquid. Stokes-Einstein equation, which linearly correlates the diffusion coefficient of a spherical molecule and macroscopic viscosity, was shown to work well for the [EMIM][OAc]-DMSO mixture. The influence of DMSO on the "anomalous" diffusion in [EMIM][OAc] ("quick" cation vs "slow" anion) was investigated; it was demonstrated that DMSO makes the cation diffusion slower. All parameters studied showed relatively small deviations from the ideal mixing rule behavior (from 20% to 50% difference between experimental and theoretically predicted results), confirming weak interactions between the components.

Effects of dimethyl sulfoxide on lipid membrane electroporation.

Pores can be generated in lipid membranes by the application of an external electric field or by the addition of particular chemicals such as dimethyl sulfoxide (DMSO). Molecular dynamics (MD) has been shown to be a useful tool for unveiling many aspects of pore formation in lipid membranes in both situations. By means of MD simulations, we address the formation of electropores in cholesterol-containing lipid bilayers under the influence of DMSO. We show how a combination of physical and chemical mechanisms leads to more favorable conditions for generating membrane pores and, in particular, how the addition of DMSO to the medium significantly reduces the minimum electric field required to electroporate a lipid membrane. The strong alteration of membrane transversal properties and the energetic stabilization of the hydrophobic pore stage by DMSO provide the physicochemical mechanisms that explain this effect.

The Influence of Nucleotide Sequence and Temperature on the Activity of Thermostable DNA Polymerases

Extension rates of a thermostable, deletion-mutant polymerase were measured from 50°C to 90°C using a fluorescence activity assay adapted for real-time PCR instruments. Substrates with a common hairpin (6-base loop and a 14-bp stem) were synthesized with different 10-base homopolymer tails. Rates for A, C, G, T, and 7-deaza-G incorporation at 75°C were 81, 150, 214, 46, and 120 seconds(-1). Rates for U were half as fast as T and did not increase with increasing concentration. Hairpin substrates with 25-base tails from 0% to 100% GC content had maximal extension rates near 60% GC and were predicted from the template sequence and mononucleotide incorporation rates to within 30% for most sequences. Addition of dimethyl sulfoxide at 7.5% increased rates to within 1% to 17% of prediction for templates with 40% to 90% GC. When secondary structure was designed into the template region, extension rates decreased. Oligonucleotide probes reduced extension rates by 65% (5'-3' exo-) and 70% (5'-3' exo+). When using a separate primer and a linear template to form a polymerase substrate, rates were dependent on both the primer melting temperature (Tm) and the annealing/extension temperature. Maximum rates were observed from Tm to Tm - 5°C with little extension by Tm + 5°C. Defining the influence of sequence and temperature on polymerase extension will enable more rapid and efficient PCR.

Influence of Dimethylsulfoxide on RNA Structure and Ligand Binding

Dimethyl sulfoxide (DMSO) is widely used as a cosolvent to solubilize hydrophobic compounds in RNA-ligand binding assays. Although it is known that high concentrations of DMSO (>75%) can significantly affect RNA structure and folding energetics, a thorough analysis of how lower concentrations (<10%) of DMSO typically used in binding assays affects RNA structure and ligand binding has not been undertaken. Here, we use NMR and 2-aminopurine fluorescence spectroscopy to examine how DMSO affects the structure, dynamics, and ligand binding properties of two flexible hairpin RNAs: the transactivation response element from HIV-1 and bacterial ribosomal A-site. In both cases, 5-10% DMSO decreased stacking interactions and increased local disorder in noncanonical residues within bulges and loops and resulted in 0.3-4-fold reduction in the measured binding affinities for different small molecules, with the greatest reduction observed for an intercalating compound that binds RNA nonspecifically. Our results suggest that, by competing for hydrophobic interactions, DMSO can have a small but significant effect on RNA structure and ligand binding. These effects should be considered when developing ligand binding assays and high throughput screens.

Influence of DMSO on antifungal activity during susceptibility testing in vitro

Dimethylsulfoxide (DMSO) binds within the plasma membrane of cells and increases membrane permeability. DMSO is used in antifungal (AF) susceptibility assays for water insoluble agents. DMSO was observed to cause Candida albicans to express enhanced, diminished, or no change in growth compared to control medium, suggesting DMSO could influence the efficacy of water-insoluble AF agents. The activity of 4 water soluble AF agents against 6 yeast species was tested under conditions similar to the CSLI M27-A3 method. Growth response to 0.5% and 1% DMSO was variable. In 15 of 67 AF assays, DMSO resulted in a different MIC-2 (substantial inhibition of growth) value compared to control. Two of these involved differences of two doubling dilutions. The results imply that, in some cases of water-insoluble AF drug—yeast combinations, the MIC-2 may be skewed from the more clinically relevant MIC, providing one reason for possible discordance between MIC results and clinical outcomes.

Sequential injection fluorimetric determination of Sn in juices of canned fruits

The present work describes the development of a fast and robust sequential injection fluorimetric procedure for the determination of Sn in juices of canned fruits. The developed automatic methodology is based on the complexation of Sn with 8-hydroxyquinoline-5-sulfonic acid (HQSA) to form a fluorimetric product ( λ exc = 354 nm; λ em = 510 nm). The influence of dimethylsulfoxide (DMSO) and cetylpyridinium bromide (CPB) on the sensitivity of the fluorimetric determination was evaluated. Linear calibration plots were obtained for Sn concentrations between 1 and 10 mg L −1, with a detection limit of 0.38 mg L −1. In each analytical cycle 0.006 mg of HQSA and 0.47 mg of CPB were consumed and 1.5 mL of effluent was generated. The developed methodology was applied to the determination of Sn in juices of canned fruits and the results complied with those furnished by an electrothermal atomic absorption spectrometry comparison procedure, with relative deviations lower than 5.2%. The automatic procedure exhibited good precision (R.S.D. < 1.4%) and the sampling rate was about 70 determinations per hour.

Investigation of the interaction of dimethyl sulfoxide with lipid membranes by small-angle neutron scattering

The influence of dimethyl sulfoxide (CH3)2SO (DMSO) on the structure of membranes of 1,2-dimiristoyl-sn-glycero-3-phosphatidylcholine (DMPC) in an excess of a water-DMSO solvent is investigated over a wide range of DMSO molar concentrations 0.0 ≤ X DMSO ≤ 1.0 at temperatures T = 12.5 and 55°C. The dependences of the repeat distance d of multilamellar membranes and the thickness d b of single vesicles on the molar concentration X DMSO in the L β’ gel and L α liquid-crystalline phases are determined by small-angle neutron scattering. The intermembrane distance d s is determined from the repeat distance d and the membrane thickness d b. It is shown that an increase in the molar concentration X DMSO leads to a considerable decrease in the intermembrane distance and that, at X DMSO = 0.4, the neighboring membranes are virtually in steric contact with each other. The use of the deuterated phospholipid (DMSO-D6) and the contrast variation method makes it possible, for the first time, to determine the number of DMSO molecules strongly bound to the membrane.

Influence of Dimethyl Sulfoxide on Extracellular Enzyme Production by Pleurotus ostreatus

Dimethyl sulfoxide (DMSO) is commonly used as a co-solvent to dissolve poorly water-soluble biologically active agents to assess their biological activities such as for enzyme induction. The question addressed was whether DMSO can be assumed to be an inert co-solvent. The influence of DMSO on the production of extracellular enzymes by Pleurotus ostreatus was investigated. DMSO functioned as either an inducer or a repressor, depending on the enzyme studied. The production of laccase and endo-1,4-beta-xylanase increased by 29 and 250%, respectively, in presence of DMSO. However, DMSO repressed the activities of manganese peroxidase, beta-glucosidase, beta-xylanase, and endo-1,4-beta-glucanase by 30, 33, 99 and 16%, respectively. These results raise concerns about the interpretation of bioactivity measurements when DMSO is assumed to function as an inert co-solvent to solubilize water-insoluble molecules.

In vitro permeation of diclofenac sodium from novel microemulsion formulations through rabbit skin

AbstractIn order to increase topical penetration of the nonsteroidal anti‐inflammatory drug, diclofenac sodium, new microemulsion formulations were prepared to increase drug solubility and in vitro penetration of the drug. The influence of dimethyl sulfoxide and propylene glycol were also investigated as enhancers on the in vitro penetration of diclofenac sodium using Franz diffusion cells using excised dorsal rabbit skin. Factorial randomized design was performed to analyze the results of in vitro permeation studies. Microemulsions prepared with isopropyl alcohol were superior to those prepared with propanol. Enhancers had different effects depending on the formulation. Propylene glycol was superior to dimethyl sulfoxide when incorporated into isopropyl alcohol microemulsion, whereas dimethyl sulfoxide was superior to propylene glycol in propanol microemulsions. There were no observable histopathological differences between the skin of the control group and the treated groups at the light microscope level due to swelling of the skin tissue. The present study shows that microemulsion formulations containing isopropyl alcohol as co‐surfactant and propylene glycol as enhancer represent a promising approach for a topical vehicle for diclofenac sodium. Drug Dev. Res. 65:17–25, 2005. © 2005 Wiley‐Liss, Inc.

Molecular Simulation Study on the Influence of Dimethylsulfoxide on the Structure of Phospholipid Bilayers

Molecular dynamics simulations of dipalmitoylphosphatidylcholine (DPPC) lipid bilayer/water systems were performed in the presence of dimethylsulfoxide (DMSO) at 2, 5, 10, and 100 mol % DMSO (lipid-free basis). The equilibrium structure and several dynamic properties were determined for these systems. Results show that DMSO penetrates much deeper into the bilayer than water does. It is also found that DMSO molecules do not interact with the polar groups of the lipid headgroup, but exhibit a preference to remain either directly below the headgroup or in the aqueous phase, which is a consequence of the chemical characteristics of DMSO. As the temperature increases, a higher DMSO concentration is observed in the bilayer side of the interface. The area per headgroup in the presence of DMSO is significantly increased from 66.8 Å 2 for the pure bilayer to as high as 87.0 Å 2 at 10 mol % DMSO at 350 K. DMSO hydrogen-bonds strongly with water and exhibits unfavorable interactions with the polar headgroups of DPPC, thereby inducing a dehydration of the headgroups.

High-throughput screening of pKa values of pharmaceuticals by pressure-assisted capillary electrophoresis and mass spectrometry.

A high-throughput pKa screening method based on pressure-assisted capillary electrophoresis (CE) and mass spectrometry (MS) is presented. Effects of buffer type and ionic strength on sensitivity and pKa values were investigated. Influence of dimethyl sulfoxide (DMSO) concentration present in the sample on effective mobility measurement was examined. A series of ten volatile buffers, covering a pH range from 2.5 to 10.5 with the same ionic strength, was employed. The application of volatile background electrolytes resulted in significant signal increase as compared with commonly used non-volatile phosphate buffers. In general, the CE/MS system provided a ten-fold higher sensitivity than conventional UV detection. The newly developed CE/MS method offers high-throughput capacity by pooling a number of compounds into a single sample. Simultaneous measurement of more than 50 compounds was readily achieved in less than 150 min. The measured pKa values are consistent with the published data obtained from the CE/UV method and are also in good agreement with data generated by other methods. Other advantages of using CE/MS for pKa screening are illustrated with typical examples, including poorly soluble compounds and non-UV-absorbing compounds.

Characterisation of atovaquone resistance in Leishmania infantum promastigotes

Atovaquone, an antiparasitic agent, could possibly represent an alternative therapy after relapse following classical treatment for visceral leishmaniasis. Atovaquone-resistant strains were selected in vitro by stepwise drug pressure to study the mechanism of resistance in Leishmania. Characteristics of a promastigote strain resistant to 250μg/ml of atovaquone were compared with those of the wild type (WT) strain. Resistant strains were shown to have a high level of resistance (45 times). They were stable in drug-free medium for 6 months, and showed no cross-resistance with other antileishmanial drugs. Rhodamine uptake and efflux were studied. They were not modified in the resistant strain, indicating the absence of P-glycoprotein overexpession. The effect of atovaquone on membrane lipidic composition was determined in both WT and atovaquone-resistant promastigotes. Analysis of lipid composition of the atovaquone-resistant strain showed that sterol biosynthesis was decreased in atovaquone-resistant parasites. Cholesterol was found to be the major membrane sterol as opposed to the WT strain. Cholesterol, due to its ordering effect, could decrease membrane fluidity and subsequently block the passage of atovaquone through the membrane. Increased membrane cholesterol content and altered drug membrane fluidity resulted from possible decrease of ergosterol biosynthesis by atovaquone, incorporation of cholesterol by promastigotes in the culture medium, solubilisation of atovaquone by cholesterol and co-passage of the two compounds or influence of dimethylsulfoxide. These results indicate that different cellular alterations may participate in the resistant phenotype, by altering drug membrane permeability.

Influence of dimethylsulfoxide on tylosin production in Streptomyces fradiae.

The polyketide aglycone, tylactone (protylonolide), does not normally accumulate during tylosin production in Streptomyces fradiae, suggesting that the capacity of the organism to glycosylate tylactone exceeds the capacity for polyketide synthesis. Consistent with this model, tylosin yields were significantly increased (due to bioconversion of the added material) when exogenous tylactone was added to fermentations. However, tylosin yield improvements were also observed (albeit at lower levels) in solvent controls to which dimethylsulfoxide (DMSO) was added. At least in part, the latter effect resulted from stimulation of polyketide metabolism by DMSO. This was revealed when the solvent was added to fermentations containing the tylA mutant, S. fradiae GS14, which normally accumulates copious quantities of tylactone.

DMSO-induced dehydration of DPPC membranes studied by X-ray diffraction, small-angle neutron scattering, and calorimetry

The influence of dimethyl sulfoxide (DMSO) on membrane thickness, multilamellar repeat distance, and phase transitions of 1,2-dipalmitoyl- sn-glycero-3-phosphatidylcholine (DPPC) was investigated by X-ray diffraction and small-angle neutron scattering (SANS). The differential scanning calorimetry (DSC) study of water freezing and ice melting was performed in the ternary DPPC/DMSO/water and binary DMSO/water systems. The methods applied demonstrated the differences in membrane structure in three sub-regions of the DMSO mole fraction ( X DMSO): from 0.0 to 0.3 for the first, from 0.3 to 0.8 for the second, and from 0.9 to 1.0 for the third sub-region. The thickness of the intermembrane solvent at T =20°C decreases from 14.4±1.8 Å at X DMSO=0.0 to 7.8±1.8 Å at X DMSO=0.1. The data were used to determine the number of free water molecules in the intermembrane space in the presence of DMSO. The results for 0.0≤ X DMSO≤0.3 were explained in the framework of DMSO-induced dehydration of the intermembrane space.

Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts.

Niemann-Pick type C (NPC) fibroblasts present a large concentration of cholesterol in their cytoplasm due to a still unidentified deficiency in cholesterol metabolism. The influence of dimethylsulfoxide (DMSO) on the amount of intracellular cholesterol was measured in 8 cultures of normal fibroblasts and in 7 fibroblast cultures from NPC patients. DMSO was added to the fibroblast cultures at three different concentrations (1, 2 and 4%, v/v) and the cultures were incubated for 24 h. Sphingomyelinase activity was significantly increased in both groups of cells only when incubated with 2% DMSO (59.4 +/- 9.1 and 77.0 +/- 9.1 nmol h-1 mg protein-1, controls without and with 2% DMSO, respectively: 47.7 +/- 5.2 and 55.8 +/- 4.1 nmol h-1 mg protein-1. NPC without and with 2% DMSO, respectively). However, none of the DMSO concentrations used altered the amount of cholesterol in the cytoplasm of NPC cells (0.704 +/- 0.049, 0.659 +/- 0.041, 0.688 +/- 0.063 and 0.733 +/- 0.088 mg/mg protein, without DMSO, 1% DMSO, 2% DMSO and 4% DMSO, respectively). This finding suggests that sphingomyelinase deficiency is a secondary defect in NPC and shows that DMSO failed to remove the stored cholesterol. These data do not support the use of DMSO in the treatment of NPC patients.

Alkaloid repartition and DMSO effects on alkaloid cccumulation in Catharanthus seedlings

Summary Many studies have addressed the improvement of indole alkaloid production in Catharanthus roseus cell suspension culture, but only few of them were concerned with entire plants cultured in vitro . The aim of this work was to investigate alkaloid distribution and the influence of DMSO (dimethyl sulfoxide) on alkaloid accumulation in C. roseus seedlings grown in vitro . Thirty-day-old seedlings were cultured on hormone-free medium supplemented with DMSO and analysed by HPLC and TLC. An «abnormal» alkaloid distribution in seedling roots was characterised by the lack of catharanthine and the presence of yohimbine for the first time. Both ajmalicine and serpentine were also observed. Vindoline and catharanthine were detected in the aerial parts. The results with DMSO showed a decrease in alkaloid accumulation in both the roots and aerial parts.

NMR spectroscopic investigation of agarose oligomers produced by an α-agarase

The 13C NMR signals of various even and odd agarose oligosaccharides with either d-galactose or 3,6-anhydro-α- l-galactose at the reducing end have been assigned. The chemical shifts in water of the agaro- and the neoagaro-oligosaccharides are compared and the influence of dimethyl sulfoxide on the chemical structure of the agaro-oligosaccharides is reported. The 3,6-anhydro- l-galactose residue at the reducing end of agaro-oligosaccharides is in the hydrated form.

Influence of dimethyl sulfoxide on the kinetics of the graft copolymerization of acrylonitrile onto the jute fibers initiated by ceric ion

AbstractA study of the influence of dimethyl sulfoxide (DMSO) on the graft copolymerization of acrylonitrile (AN) onto jute fiber using ceric ion has been made. The effect of concentrations of monomer, Ce(IV) and DMSO on graft yield have been studied. Besides, the effect of time, temperature, acid, and the amount of jute fiber on graft yield has been investigated. On the basis of experimental findings, a reaction mechanism has been proposed and optimum condition for effective grafting has been suggested.

Synthesis and crystal structure of potassium tetranitrato palladate(II)

K 2 [Pd(NO 3) 4] has been prepared and its crystal structure determined by use of a CAD-4 diffractometer with monochromatic Mo Kα radiation. The space group is P2 1/ c with Z = 4; a= 7.940(2); b = 15.469(4); c = 9.453(2) Å; β = 91.10(3)°. The refinement converged to R = 0.023. The structure contains discrete complexes of [Pd(NO 3) 4] 2− with pseudosymmetry C4. Pd coordinates four oxygens from different unidentate nitrato groups. The average Pd-O distance is 2.000(7) Å. The coordination around Pd is distorted square-planar, with Pd situated 0.139 A above the plane through the four coordinated oxygens. Similar to [Pt(NO 3) 4] 2−, but in contrast with [Au(NO 3) 4] −, all four nitrato ligands are situated on the same side of the coordination plane forming a basket-like structure. This is probably due to interactions between the non-coordinated oxygens of the nitrato ligands and suitably located potassium ions. Comparison with the structure of cis-[Pd- (NO 3) 2(DMSO) 2] indicates strong ground-state trans- influence of dimethyl sulfoxide in palladium complexes.