Dimethyl Sulfoxide-d6 Solution Research Articles

Molecular switching through cooperative ionic interactions and charge assisted hydrogen bonding

Sodium 2-(2-(1-cyano-2-oxopropylidene)hydrazinyl)benzenesulfonate (NaHL) was synthesized by azocoupling of diazonium salt of 2-aminobenzenesulfonic acid with 3-oxobutanenitrile and characterized by IR, 1H and 13C NMR spectroscopies and ESI-MS analysis. In dimethylsulfoxide-d6 solution NaHL exists as a mixture of Z- and E-hydrazone forms in the amounts of 96 and 4%, respectively. Treatment of this isomeric mixture with copper(II) nitrate hydrate in the presence of ethylenediamine (en) provides unusual (E,Z) → E switching of NaHL to give [Cu(H2O)2(en)2](HL)2 (1). The process is interpreted on the basis of cooperative ionic interactions and resonance assisted hydrogen bonding (RAHB) → charge assisted hydrogen bonding (CAHB) transition.

Amino acid-based squaramides for anion recognition

Eight receptors 1–8 comprising an l-lysine scaffold modified at N- and C-termini with aliphatic alkyl chains and N,N′-alkyl amides, respectively, and bearing squaramide moieties on the amino acid side chain were synthesised by a combination of solid- and solution-phase chemistries and shown to complex various anions in 0.5% H2O in dimethyl sulfoxide-d6 solution. All of the receptors were found to bind Cl− , AcO− and BzO− via hydrogen-bond or acid–base interactions with the squaramide protons; however, 1 was found to bind to via hydrogen bonds formed between the anion and both the squaramide and amide NH moieties. Moreover, modification of both the N- and C-termini of the amino acids with different alkyl substituents had a negligible effect on their anion-binding properties while simultaneously conferring lipophilicities in a range that is optimal for molecules to behave as ‘drug-like’ systems as defined by Lipinski's rule of five. The results of this study demonstrate the versatility of such amino acid receptors as building blocks in the field of anion recognition.

On the interaction between mercury(II) salts and 3-methylpyrazoline-5-one. The first crystal structure of a cyclic organomercuric compound with a dimercurated methylenic carbon atom

Synthesis and characterization of two types of novel organomercury derivatives of 3-methylpyrazoline-5-one (MepzH2-one), (XHg)2(MepzH-one) (X = Cl−, Br−) and Hg(MepzH-one)2 are described. The 1H and 13C NMR data revealed existence of dimercurated compounds in the dimethylsulfoxide-d6 solution. NMR spectra confirmed that the mercuration took place at the C-4 atom of the pyrazole ring. X-ray crystal structure analysis of 4,4-bis(chloromercurio)-3-methylpyrazoline-5-one revealed almost linear coordination of both mercury atoms [Hg–C 2.099(6) and 2.104(5) ; Hg–Cl 2.330(2) and 2.338(2) ; C–Hg–Cl 171.1(2) and 174.4(2)°]. The slight deviation from linearity is caused by contacts with nitrogen or oxygen atoms from the neighbouring molecule [Hg\(\cdots\)N 2.768(5) and Hg\(\cdots\)O 2.748(5) ]. The molecules are interconnected by hydrogen bonds N–H\(\cdots\)Cl of 3.286(5) .

Synthesis, characterization and X-ray structural, electrochemical and Mössbauer study of mercury(II) complexes with 1′-(diphenylphosphino)ferrocenecarboxylic acid

Abstract Reaction of mercury(II) halides with 1′-(diphenylphosphino)ferrocenecarboxylic acid (Hdpf) affords [HgX2(Hdpf-P)2] or [HgX(μ-X)(Hdpf-P)]2 complexes (X=Cl, Br, I) depending on the stoichiometry of the educts. The complexes have been studied by IR, Mossbauer and solution NMR spectroscopy. In dimethyl sulfoxide-d6 solution, 1H- and 31P{1H}-NMR spectra indicate solvolytic cleavage of the mercury(II)–phosphine bond resulting in partial decomplexation of the phosphine ligand. Electrochemical measurements in donor solvents also confirm the presence of a non-coordinated ligand since the electrochemical behavior is the superposition of that of the product of solvolysis and of the ligand. X-ray structural analysis, of the representatives of both types, was carried out: [HgBr2(Hdpf-P)2] ([C46H38Br2Fe2HgO4P2], monoclinic; space group C2/c, a=19.453(1), b=13.704(1), c=17.929(2) A; β=114.953(7)°; Z=4) and [HgBr(μ-Br)(Hdpf-P)]2·2CH3CO2H ([C54H54Br4Fe2Hg2O12P2], triclinic; space group P, a=9.442(1), b=11.7101(9), c=14.806(1) A; α=109.692(7), β=92.494(9), γ=101.883(7)°; Z=1). The P-monodentate coordination of the phosphinocarboxylic ligand was confirmed in both cases, the carboxyl group being involved in hydrogen bonding to carboxyl groups of either neighboring ligand or solvating acetic acid. The expected Br2P2 and Br3P tetrahedral donor sets around Hg(II) are the subject of different degrees of deformation due to steric effects. 57Fe Mossbauer spectra of the complexes also point to the P-coordination of the ferrocenylphosphino ligand, as follows from the decrease of the quadrupole splitting and only a slight variation of the isomer shift on going from ligand to complex.

NMR study of a lymphocyte differentiating thymic factor. An investigation of the Zn(II)-nonapeptide complexes (thymulin).

Detailed investigations of a serum peptide (less than Glu1-Ala2-Lys3-Ser4-Gln5-Gly6-Gly7-Ser8-++ +Asn9) were carried out by 1H and 13C NMR spectroscopy to elucidate the structure of the complex formed with Zn(II), thymulin, which has been found to be active in vivo. These experiments were performed in dimethyl sulfoxide-d6 solution at different metal:peptide ratios. The results suggest the following conclusions. (i) The Zn(II) complexation corresponds to a fast exchange on the NMR time scale. (ii) The evolution of 1H and 13C NMR chemical shifts indicates the existence of two types of complexes: a 1:2 species associating two peptide molecules and one Zn(II) ion and a complex with 1:1 stoichiometry. The former is predominant for metal:peptide ratios below unity. (iii) In the 1:2 complex, Zn(II) is coordinated by the Ser4-O gamma H and Asn9-CO2- sites, while in the 1:1 complex, Ser8-O gamma H is the third ligand to the Zn(II) ion. The results are compared with those for the [Ala4] and [Ala8] analogues, and those for the complexes of thymulin with other metal ions (Cu2+ and Al3+) in terms of its biological activity. These comparative studies suggested that the 1:1 complex is the only conformation recognized by the antibodies.

Estimation of Dissociation Constants (pKa'S) of Oximes from Proton Chemical Shifts in Dimethyl Sulfoxide Solution

In connection with structure-activity studies of insecticidal methyl carbamoyloxime acetylcholinesterase inhibitors, a straightforward approach to estimating pKa values of a series of precursor oximes and thiohydroximates has been developed. The pKa values of oximes correlate well with the proton chemical shifts of the oximino proton (δOH) in dilute dimethyl sulfoxide-d6 solution. The relationship pKa=29.10 – 1.63δOH was developed from δOH and pKa data for 20 compounds available either from the literature or derived experimentally from half-neutralization potentials (ΔHNP). Using this relationship, pKa values of more than 200 hydroximino compounds were calculated. The relationship has been extended to also include phenols: pKa=28.15 – 1.55δOH – 3.96l(phenol), where l(phenol) is an indicator variable indicating application of the equation to either a phenol [l(phenol)=1] or an oxime [l(phenol)=0].

NMR study of thymulin, a lymphocyte differentiating thymic nonapeptide. Conformational states of free peptide in solution.

The nonapeptide less than Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn (formerly called serum thymic factor) is a factor produced by the thymic epithelium, which needs a zinc ion to express its immunoregulatory properties. We report here on 1H and 13C NMR investigation of the conformational properties of the free peptide in aqueous medium and in dimethyl sulfoxide-d6 solution by a combination of homo- and heteronuclear one- and two-dimensional experiments. The various resonances have been assigned in a straightforward manner on the basis of 1H,1H COSY spectroscopy for the recognition of the proton spin systems; two-dimensional NOESY spectra with the correlation peaks across amide bonds and for the amino acid sequence assignment; amide bonds and for the amino acid sequence assignment; 13C,1H COSY experiments using selective polarization transfer from 1H- to 13C-nucleus via the 13C,1H long-range couplings for the attribution of the carboxyl and carbonyl groups; and 13C,1H COSY experiments with selective polarization transfer via the 13C,1H direct couplings for the assignment of all the aliphatic carbons. Other experiments such as pH-dependent chemical shifts, combined use of multiple and selective proton-decoupled 1H and 13C NMR spectra, the temperature and the concentration dependence of the proton shifts of the amide resonances, the solvent dependences of peptide carbonyl carbon resonances, and comparison of the spectra with three different analogues were performed. In aqueous solution, the data are compatible with the assumption of a highly mobile dynamic equilibrium among different conformations, whereas in dimethyl sulfoxide-d6, a more rigid structure is found involving three internal hydrogen bonds. These observations provide an insight into the conformational tendencies of this peptidic hormone in two different media.

Two-dimensional 1H NMR studies of rat atrial natriuretic factor(1–23)

Using a variety of two-dimensional NMR methods, the 1H NMR resonances of rat ANF(1–23) in dimethyl sulfoxide-d6 solution have been assigned. Two-dimensional phase sensitive correlated spectroscopy was used to identify protons that are scalar coupled and were also used to obtain coupling constants (3JNH-αCH) in complicated regions of the spectra. Relayed coherence transfer experiments proved useful in identifying the connectivities between the NH and β-protons of the same amino acid residue. Finally, phase sensitive 2D NOE experiments allowed the identification of protons close in space between adjacent residues, thus providing the sequential assignments as well as conformational information. These preliminary results (chemical shifts, coupling constants, NOEs) were analyzed in terms of possible polypeptide secondary structures and were found to be consistent with a β-type structure or an averaging of solution conformations (random coil).

Segmental motion in pseudomonic acid A: a carbon-13 spin-lattice relaxation time study at two field strengths.

The mobility of pseudomonic acid A in dimethyl sulfoxide-d6 solution has been determined from 13C spin-lattice relaxation time measurements at two field strengths. The central tetrahydropyran ring reorientates isotropically with a rotational correlation time of approximately 280 picoseconds/ radian . Both side-chains exhibit marked segmental motion with correlation times decreasing to only approximately 50 picoseconds/ radian at the end of the nonanoic acid side-chain.

NMR Spectral Study of Proton Transfer in Amitriptyline Hydrochloride–Chlordiazepoxide Hydrochloride Combinations in Dipolar Aprotic Solvent

The singlet resonance due to the two equivalent methyl groups of amitriptyline hydrochloride in dimethyl sulfoxide-d6 solution changed into a doublet with the addition of chlordiazepoxide hydrochloride. A spin decoupling experiment revealed that the doublet originated because of the emergence of observable spin-spin coupling between the tertiary amine proton and the methyl groups. The phenomenon was interpreted to be due to the nature of proton transfer caused by the relative magnitudes of the basicities of the amines in these compounds, which were determined by the inductive and steric effects of the substituents, leading to the formation of hydrogen-bonded ion-pairs in the aprotic diluent. The enthalpy of the exchange process was 6.4 ± 0.5 kcal/mole.

220 MHz Nuclear Magnetic Resonance Studies of Amygdalin and Some Related Compounds

Abstract A study of amygdalin, isoamygdalin, vicianin, amygdalinamide, amygdalinic acid, prunasin, sambunigrin, taxiphyllin, dhurrin, and holocalin has been carried out by nuclear magnetic resonance (NMR) spectrometry. Using 220 MHz spectra, the glycosides were studied in dimethylsulfoxide-d6 solution and in the presence of DO and D2O. Generally the assignments permit the following classification: The non-hydroxylic protons (including the anomeric protons) and the hydroxylic protons occur in the region from about 3.0 to 5.3 ppm; the aglycone methine hydrogen falls at about 6 ppm except for amygdalinamide and amygdalinic acid; the phenyl hydrogens are in the region of about 7 ppm. The chemical shifts and coupling constants for both OH6 and two H6 are independent of the aglycone stereochemistry, whereas the effect of the epimeric nature of the aglycone may be seen in terms of the carbohydrate portion resonances. The nature of the aglycone group may be classified as R or S, depending on the methine proton resonance. These studies should be very useful in the application of NMR to the recognition of aglycone stereochemistry and identification of amygdalin and other related cyanogenetic glycosides.