Neat DMSO Research Articles

Spectroscopic and TD-DFT studies on the chromo-fluorogenic detection of cyanide ions in organic and aquo-organic media

A new naked-eye chromogenic and fluorogenic probe KS5 has been developed for the detection of CN– ions in neat DMSO and H2O:DMSO (1:1 v/v) media. The probe KS5 exhibited selectivity towards CN– and F− ions in organic and high selectivity towards CN– ions in aquo-organic media resulting in a colour change from brown to colourless and a turn-on fluorescence response. The probe could able to detect CN– ions via a deprotonation process, which was conceived by consecutive addition of hydroxide and hydrogen ions and confirmed using 1H NMR studies. The limit of detection (LOD) of KS5 towards CN– ions were in the range of 0.07–0.62 µM in both these solvent systems. Suppression of intra-molecular charge transfer (ICT) transition and photoinduced electron transfer (PET) process of KS5 by the added CN– ions are responsible for the chromogenic and fluorogenic changes observed, respectively. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) calculations strongly supported the proposed mechanism along with the optical properties of the probe before and after the addition of CN– ions. To prove the practical applicability, KS5 was successfully utilized to detect CN– ions in cassava powder and bitter almonds as well as to determine CN– ions in various real water samples.

Avoid missing pKas: High-throughput workflow using solution pH-metric in tandem with UV-metric measurements

We describe a new high-throughput automated pKa workflow using potentiometry starting with 10 mM DMSO stock (solution pH-metric). Two approaches using either neat DMSO stock solution or removal of DMSO were evaluated with different sample amounts and cosolvent schemes. These were validated against traditional potentiometric measurements for optimal conditions. Further, we detail how high throughput solution pH-metric experiments are performed in tandem with established UV-metric measurements to capitalize on the advantages of both approaches. This new workflow maintains the sample and time savings required for measuring a large number of samples in a drug discovery setting, while avoiding “missing pKas” due to lack of sufficient UV chromophores. The combination of the two assays is key to tackle the challenges of low solubility, overlapping pKas, and preliminary assignment of pKas for Structure-Activity Relationship (SAR) understanding.

3-Hydroxy-2-naphthoic hydrazide as a probe for fluorescent detection of cyanide and aluminium ions in organic and aquo-organic media and its application in food and pharmaceutical samples

The commercially available fluorophore, 3-hydroxy-2-naphthoic hydrazide (RS2), has rationally been selected for the study, which displays a rapid fluorescent response and high sensitivity for CN− and Al(III) ions in neat DMSO and H2O-DMSO (1:1 v/v) media. The addition of CN− to RS2 triggers an enhancement in fluorescence at 505 nm (green fluorescence), while the addition of Al(III) increases the fluorescence of the probe with a blue-shift of emission maximum by 25 nm (bluish-green fluorescence). The probe's action was investigated by 1H NMR titrations that indicate deprotonation of OH and NH moieties by these ions. 27Al NMR of RS2-Al(III) complex suggests an octahedral geometry for the complex. The sensitivity of the fluorescent-based assays in aq. DMSO medium, 0.8 µM for CN− and 1.9 µM for Al(III) ions are far below the limits in the World Health Organization guidelines for drinking water. RS2 detects Al(III) by the chelation-enhanced fluorescence (CHEF) mechanism. Besides, RS2 was successfully applied to detect CN− and Al(III) ions in food materials and pharmaceutical samples, respectively.

Development of simple imine based probe for selective fluorescent cyanide sensing with red-emission in solid and solution phases

In the present work, an easy to make imine based receptor (3,3′(((5-(tert-butyl)-2-hydroxy-1,3-phenylene)bis(methanylylidene))bis(azanylylidene))bis(2-aminomaleonitrile)) (CNA) has been synthesized in good yield and characterized by spectral methods. CNA showed rapid, selective and sensitive naked-eye dual channel response (colorimetric and fluorogenic) towards cyanide ion. The receptor exhibited instantaneous colour change upon addition of cyanide ion based on deprotonation of phenolic –OH moiety in neat DMSO, 30% aq. DMSO and solid media. Interestingly, CNA showed red-emission (640 nm < λem < 677 nm) upon treatment with cyanide ion in all these media. Limit of detection of CNA for cyanide ion was determined to be 0.5 μM, which is much lower than the permissible limit of cyanide in drinking water as recommended by the World Health Organization. The fabricated cotton swabs and test strips demonstrated excellent selectivity towards cyanide ion in aqueous solution. Further, CNA is suitable for dual channel detection of cyanide ion in food materials. Furthermore, the observable colour change of the probe upon binding with cyanide ion has successfully been integrated with a smartphone Colour Picker app to estimate cyanide ions.

A simple imine as a dual-channel chemosensor for detection of CN− and HS− ions via different mechanisms in organic and aquo-organic media

An imine based easy to make receptor (R) has been synthesized and characterized, which senses CN− and HS− ions selectively and sensitively in neat DMSO and H2O:DMSO (60:40 v/v) media. Upon treatment with these ions, the receptor exhibited instantaneous colour change from yellow to colourless and a fluorescence enhancement and these optical changes are easily detected by direct visualization. Further, other competitive anions didn’t display any observable colour and fluorescence changes, indicating the receptor's high selectivity towards CN− and HS− ions. The nucleophilic addition of cyanide ion to the imine bond induces an increase in fluorescence, while HS− ion triggered cleavage of the imine bond, producing enhancement in fluorescence in both the media. The limits of detection for CN− and HS− ions were calculated to be 0.9 and 0.7 μM, respectively, which are lower than the permissible limit of these ions in drinking water set by the World Health Organization (WHO). The receptor has fruitfully been applied for the detection of these ions in live HeLa cells.

Counterintuitive solvation effect of ionic-liquid/DMSO solvents on acidic C-H dissociation and insight into respective solvation.

How would acidic bond dissociation be affected by adding a small quantity of a weakly polar ionic liquid IL (the “apparent” or “measured” dielectric constant ε of the IL is around 10–15) into a strongly polar molecular solvent (e.g., ε of DMSO: 46.5), or vice versa? The answer is blurred, because no previous investigation was reported in this regard. Toward this, we, taking various IL/DMSO mixtures as representatives, have thoroughly investigated the effects of the respective solvent in ionic–molecular binary systems on self-dissociation of C–H acid phenylmalononitrile PhCH(CN)2via pKa determination. As disclosed, in this category of binary media, (1) no linear correspondence exists between pKa and molar fractions of the respective solvent components; (2) only ∼1–2 mol% of weakly polar ILs in strongly polar DMSO make C–H bonds even more dissociative than in neat DMSO; (3) a small fraction of DMSO in ILs (<10 mol%) can dramatically ease acidic C–H-dissociation; and (4) while the DMSO fraction further increases, its acidifying effect becomes much attenuated. These findings, though maybe counterintuitive, have been rationalized on the basis of the precise pKa measurement of this work in relation to the respective roles of each solvent component in solvation.

Mizoroki–Heck Cross-Coupling of Bromobenzenes with Styrenes: Another Example of Pd-Catalyzed Cross-Coupling with Potential Safety Hazards

The potential safety hazards associated with the Mizoroki–Heck cross-coupling of bromobenzenes with styrenes were evaluated. The heat output from the reaction in various solvents was comparable in a variety of solvents; however, the rate of reaction was significantly faster in the presence of water. Thermal stability evaluation of the postreaction mixtures in DMSO and 3:1 DMSO/water by differential scanning calorimetry indicated that the onset temperatures of thermal decomposition were significantly lower than that of neat DMSO. Evaluation of the substrate scope revealed that the substitution pattern on the bromobenzene did not affect the heat output. The reaction rate of electron-deficient bromobenzenes was slower than that of the electron-rich bromobenzenes. In general, substituted styrenes afforded similar magnitudes of exotherms; however, the reaction rate of bromobenzene with 2-methylstyrene was significantly slower than the other studied styrenes. The predicted heat of reaction using the density fun...

Synthesis, structural elucidation and DNA binding profile of Zn(II) bis-benzimidazole complexes

Complexes of zinc (II) (L1ZnBr2, L2ZnBr2) were prepared in good yields using bis-benzimidazole ligands with olefinic bridges and different substituents on the nitrogen atoms in the benzimidazole cores (L1=H, L2=Bz). The crystal structure of L2 was determined, showing that both benzimidazole rings and the carbon atoms of the olefinic bridge are coplanar with a slight deviation and that the benzyl substituent is perpendicular to this plane. Also, the crystal structure of L1ZnBr2 was determined showing that in coordinated L1, benzimidazole rings are out the plane with respect to the olefinic bridge, allowing their coordination through the nitrogen atoms to get a strain-free seven-membered ring, achieving a distorted tetrahedral geometry. Both crystal structures of L2 and L1ZnBr2 exhibit π-π stacking interactions that hold their supramolecular arrangement. All ligands and complexes were fully characterized. Additionally, through DNA binding studies using absorption spectral titrations it was possible to determine a slight hypochromism and bathochromism when ligands and complexes interact with calf thymus DNA in neat DMSO and 3% DMSO/Tris-HCl buffer, the spectral changes being consistent with partial intercalation. The intrinsic binding constant Kb of ligands and complexes are reported for each medium.

Tert‐Butyl Nitrite Mediated Expeditious Methylsulfoxidation of Tetrazole‐amines with DMSO: Metal‐free Synthesis of Antifungal Active Methylsulfinyl‐1H‐tetrazole Derivatives

AbstractA tert‐butyl nitrite mediated methyl‐sulfoxidation of tetrazole‐amines in neat DMSO or methyl‐sulfinyl derivatives is revealed for the first time. The reaction exhibits good group tolerance, as well as highly selectivity to sulfinyl substitutions. This new protocol provides an expeditious and operationally simple procedure for C−S(O) bond construction. Preliminary bioactivity evaluation on selected products shows promising antifungal activities.magnified image

Insights into the photophysics of zinc phthalocyanine and photogenerated singlet oxygen in DMSO-water mixture

This research was focused on the effects of DMSO-water ratio on the photophysics of the sensitizer Zn phthalocyanine (ZnPc) and on the photogenerated singlet oxygen. To reach this objective optical absorption, flash photolysis and time-resolved phosphorescence were used. Potential dye accumulation at the surface of the sample was studied by surface-tension measurements and at the chosen concentration no such effects were found. It was established that the sharp drop of dye absorbance at ∼40% water content is produced by dye dimerization, probably induced by a re-clustering of molecules in the solvent composition. When water runs over 0–80% range the dye triplet lifetime follows a sigmoid evolution with an inceptive plateau at 120μs and a sharp decrease in the 25–35% water range. Complementary experiments in neat DMSO established that while the ground dye molecules strongly quench the dye triplet states they do not significantly quench singlet oxygen. Experiments also showed that previous reported behavior of the lifetime of photosensitized singlet oxygen, exhibiting a prominent peak in the range 20–40% of water content is a common feature for both water soluble and insoluble solvates. The work outlines the hypothesis of a DMSO first solvation shell around the solvated dye molecules for a water content less than 25% and of a molecular re-organisation of the solvent taking place beyond this point, which induces important variations of photophysical quantities.

An imidazolyl-pyreno-imidazole conjugate as a cyanide sensor and a set-reset memorized sequential logic device.

In this work a pyrenyl-bisimidazole receptor has been synthesized and fully characterized by standard analytical tools and spectroscopic techniques including single crystal X-ray crystallography. Crystal structure analysis shows the occurrence of strong π-π and CH-π interactions among the adjacent Py-BiimzH2 units. Moreover, each NH proton on the imidazole ring is involved in strong intermolecular hydrogen bonding interactions with N atoms of the neighboring unit forming infinite chains. The absorption and both steady state and time-resolved emission properties of the compound were found to be modulated to a significant extent by selective inorganic anions and transition metal cations in solution. Theoretical calculations employing density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were carried out and good correlation between the experimental and the TD-DFT calculated results led to the accurate assignment of the main absorption and emission bands of the original compound as well as its anionic and metal complexes. More importantly, the compound can act as an efficient ratiometric optical chemosensor for CN(-) in H2O-DMSO (9 : 1) media. The anion sensing properties of the receptor was thoroughly investigated in both neat DMSO as well as mixed H2O-DMSO (9 : 1) media through different channels. From the response profiles in terms of absorption or emission intensity and wavelength towards inorganic ions (Cu(2+) and CN(-)), we developed a molecular system which can mimic sequential Boolean logic functions of XOR, OR, XNOR and NOR logic gates. Moreover, we were able to construct a memory device which nicely demonstrates the "Write-Read-Erase-Read" behavior.

Raman scattering and DFT calculations used for analyzing the structural features of DMSO in water and methanol

We report the concentration dependent Raman spectra of neat dimethyl sulfoxide [(CH3)2SO, DMSO] and its binary mixtures with water (W)/methanol (M) in both ν(SO) and ν(C–H) regions. The ν(SO) line profile of neat DMSO was resolved into four component peaks at 1036, 1044, 1054 and 1064 cm−1 and assigned to different dimeric species of neat DMSO. A careful analysis of the Raman spectra of DMSO with water in the ν(SO) region at different concentrations reveals that upon dilution, an additional peak is observed at ~1017 cm−1 (lower side of the peak ~1036 cm−1) which is attributed to the hydrogen bonding of DMSO with water. For the highest dilution case (χ = 0.1 of DMSO), hydrogen bonded species and symmetric stretching of the dimeric ν(SO) mode were obtained which suggest that DMSO exists in dimer form even at low concentration of DMSO. The significant blue shifting of the C–H frequency due to C–H⋯O hydrogen bonding was also obtained in the case of both solvents. Our experimental results imply the existence of the dimer form of DMSO in neat as well as at χ = 0.1 of DMSO. In order to simulate and validate our experimental findings, detailed ab initio and density functional theory (DFT) calculations were also performed to obtain the ground state geometries of neat DMSO, self-associated dimer, trimer and their hydrogen bonded complexes with water and methanol. Our calculated structure of DMSO in dimer and trimer form reports a more accurate and stable geometry, in comparison to earlier calculation on these structures. Overall in this study nice spectra–structure correlations were obtained.

Conception through Build of an Automated Liquids Processing System for Compound Management in a Low-Humidity Environment

Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield, Connecticut, was built to accommodate all compound solution-based operations following dissolution in neat DMSO. Process analysis resulted in the design of two nearly identical conveyor-based subsystems, each capable of executing 1400 × 384-well plate or punch tube replicates per batch. Two parallel-positioned subsystems are capable of independent execution or alternatively executed as a unified system for more complex or higher throughput processes. Primary ALPS functions include creation of high-throughput screening plates, concentration-response plates, and reformatted master stock plates (e.g., 384-well plates from 96-well plates). Integrated operations included centrifugation, unsealing/piercing, broadcast diluent addition, barcode print/application, compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key features included instrument pooling for increased capacity or fail-over situations, programming constructs to associate one source plate to an array of replicate plates, and stacked collation of completed plates. Due to the hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity humidity environment. The activities described are the collaborative efforts that contributed to the specification, build, delivery, and acceptance testing between Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor, Thermo Scientific Laboratory Automation (Burlington, ON, Canada).

Dimeric Self‐Assembly of Pyridyl Guanidinium Carboxylates in Polar Solvents

A series of pyridyl guanidinium-carboxylates has been prepared and the dimeric self-assembly of these studied in H(2)O/DMSO mixtures, principally using dilution isothermal calorimetry. Compounds 5 and 6, incorporating an aromatic ring in the "tethering" region between the guanidinium and carboxylate groups, demonstrate the strongest dimerisation in neat DMSO. X-ray crystal structures of 5 and 6 reveal two different dimerisation architectures in the solid-state, but both involve carboxylate-guanidinium salt bridges as anticipated, and π-π interactions. Compounds 10-16 incorporating peptidic fragments between the guanidinium and carboxylate groups, showed reduced dimerisation strength with increased amino acid content, but also sustained dimerisation under increasingly aqueous conditions, up to 50% H(2)O/DMSO in the case of 14 and 15. The extent of our study in H(2)O/DMSO mixtures was determined by substrate solubility of 10-16, and not the limit of self-assembly.

Crystal structure, optical, magnetic, and photochemical properties of the complex pentakis(dimethyl sulfoxide)nitrosylchromium(2+) hexafluorophosphate

The nitrosyl complex [Cr(dmso) 5(NO)](PF 6) 2 ( 1) (dmso = dimethyl sulfoxide) has been prepared by the solvolysis of [Cr(NCCH 3) 5(NO)](PF 6) 2 in neat dmso. The optical absorption spectrum of 1 in dmso shows maxima at 734, 567, 450, 413, and 337 nm. Continuous photolysis of 1 with λ = 365–580 nm light in dmso solution results in a release of NO with quantum yield, Φ, in the range 0.034–0.108 mol Einstein −1. Irradiation of a deoxygenated CH 3CN solution of [Cr(NCCH 3) 5(NO)](PF 6) 2 in the presence of excess of [Fe(S 2CNEt 2) 2] results in a transfer of NO to the iron centre as shown from the characteristic EPR spectrum of [Fe(S 2CNEt 2) 2(NO)] with A iso( 14N) = 12.2 × 10 −4 cm −1. The EPR parameters of 1 were determined: g iso, g ‖ and g ⊥ : 1.96725, 1.91881(4) and 1.992763(2); A iso( 53Cr), A ‖ ( 53Cr) and A ⊥( 53Cr): 22.8 × 10 −4, 39 × 10 −4 and 15.8 × 10 −4 cm −1; A iso( 14N), A ‖ ( 14N) and A ⊥( 14N): 5.9 × 10 −4, 2 × 10 −4 and 7.540(4) × 10 −4 cm −1.

Solvation-Shell Effect on the Cyanine-Dye Fluorescence in Binary Liquid Mixtures

The steady-state fluorescence anisotropy and the relative quantum yield of fluorescence of cyanine dyes, 3,3′-diethyl-thiacarbocyanine iodide (DTCI) and chloride (DTCC), were measured in toluene/dimethyl sulfoxide (DMSO) liquid mixtures. It has been found that in toluene-rich mixtures the fluorescence quantum yield of DTCC is larger by about one order of magnitude than that of DTCI, the fluorescence quantum yields being the same for both cyanines in neat DMSO. Estimations based on the Perrin formula show that on decreasing DMSO volume fraction (less than 20 vol.%) the size of the preferential solvation shell around the DTCI increases up to 23 DMSO molecules at 3 vol.% DMSO as the solvation shell of DTCC does not vary. The influence of nearby solvent environment on the cyanine dye photophysics can be explained in terms of the Onsager model by taking into account the effect of the dynamic properties of DMSO solvation shell on the dye fluorescent rate constant.

Ligand photolysis and recombination of (dimethylsulfoxide) 2Fe(II)porphyrin complexes

Steady-state optical absorption and nanosecond transient absorption spectromcopy have been employed to examine ligand photolysis and recombination of (dimethylsulfoxide) 2Fe(II)protoporphyrinIX ((DMSO) 2Fe(II)PPIX), (DMSO) 2tetrakis-4-(sulfonatophenyl)-Fe(II)porphyrin. ((DMSO) 2Fe(II)4ASP) and (DMSO) 2Fe(II)uroporphyrin ((DMSO) 2Fe(II)URO) complexes in neat DMSO. The steady-state optical absorption data indicate that all three complexes are six-coordinate and low-spin. The corresponding nanosecond transient absorption data demonstrate that photo excitation of the (DMSO) 2Fe(II)PPIX and (DMSO) 2Fe(II)URO complexes results in formation of a transient species with an absorption maximum and minimum at ≈434 and ≈424 nm, respectively. These transient specientdecay exponentially with rate constants of ≈2 x 10 6s 1. Excitation of the ((DMSO) 2Fe(II)4SP, on the other hand, produces a trassient species with a broad absorption maximum centered at ≈438 nm with a minima at ≈424 nm in kinetic difference spectrum. The initially formed transient decays exponentially with rate constants of ≈1.5 x 10 5s 1. Examination of the temperature dependence of the rate constants for ligand recombination reveals that the activation enthalpy is higer for ligand recombination to the (DMSO)Fe(II)4SP complex than either the (DMSO)Fe(II)PPIX or (DMSO)Fe(II)URO complexes (8,8.6.1 and 6.8 kcal mol 1 for Fe(II)4SP, Fe(II)PPIX and Fe(II)URO, respontively). These results allow for the interpretation of the activation energy for ligand recombination in terms of electrostatic, steric and solvent interactions.

High-pressure NMR kinetics. 52. Variable-temperature and -pressure studies of solvent exchange, complex formation, and dissociation of vanadium(III) in DMSO

DMSO exchange on hexakis(dimethyl sulfoxide)vanadium(III) has been studied as a function of temperature and pressure by 1 H NMR spectroscopy at 200 and 400 MHz, in neat DMSO and in the diluent nitromethane. The following exchange parameters were obtained in neat solvent: k ex 298 /s -1 =13.1; ΔH ex ≠ /kJ mol -1 =38.5; ΔS ex =/J K -1 mol -1 =-94.5; ΔV ex =/cm 3 mol -1 =-10.1

Differential scanning calorimetry of dimethylsulphoxide-treated human stratum corneum

Differential scanning caloronetry has been employed to investigate the thermal properties of human stratum comeum. The influence of hydration and DMSO concentration on the interstitial lipid lipoprotein and protein peaks has been investigated. Hydration between 10% and 60% water had no discernible effect on these endotherms. The influence of DMSO was most pronounced on the protein peak with a concentration dependence observed for the lipoprotein peak for DMSO > 60%. The T m for the intercellular lipid peak increased linearly as a function of DMSO concentration up to 90%. Neat DMSO abolished the lipid endotherm.