Effect of Cold Atmospheric Plasma Jet Associated to Polyene Antifungals on Candida albicans Biofilms

The increasing incidence of antifungal resistance represents a great challenge in the medical area and, for this reason, new therapeutic alternatives for the treatment of fungal infections are urgently required. Cold atmospheric plasma (CAP) has been proposed as a promising alternative technique for the treatment of superficial candidiasis, with inhibitory effect both in vitro and in vivo. However, little is known on the association of CAP with conventional antifungals. The aim of this study was to evaluate the effects of the association between CAP and conventional polyene antifungals on Candida albicans biofilms. C. albicans SC 5314 and a clinical isolate were used to grow 24 or 48 h biofilms, under standardized conditions. After that, the biofilms were exposed to nystatin, amphotericin B and CAP, separately or in combination. Different concentrations of the antifungals and sequences of treatment were evaluated to establish the most effective protocol. Biofilms viability after the treatments was compared to negative control. Data were compared by One-way ANOVA and post hoc Tukey (5%). The results demonstrate that 5 min exposure to CAP showed more effective antifungal effect on biofilms when compared to nystatin and amphotericin B. Additionally, it was detected that CAP showed similar (but smaller in magnitude) effects when applied in association with nystatin and amphotericin B at 40 µg/mL and 60 µg/mL. Therefore, it can be concluded that the application of CAP alone was more effective against C. albicans biofilms than in combination with conventional polyene antifungal agents.     

Combined assay and determination of bioactivity of polyene antibiotics by flow nephelometry

The application of a simple and inexpensive method, flow nephelometry, to the assay and measurement of relative bioactivity of polyene antibiotics is reported. The responding organism was Saccharomyces cerevisiae NCYC 239 in the mid-exponential phase of growth. The relative bioactivity of the polyene antibiotics is shown to be in the order lucensomycin > nystatin > candicidin > amphotericin B > pimaracin. The method is suitable f automation.     

Theoretical investigation of the stereochemical structure of valinomycin and its hydration

The stereochemical structure of the A and B forms of valinomycin and their hydration were investigated by theoretical conformational analysis and by the Monte Carlo method. It was found that the aqueous phase has a predominant role in the stabilization of the B form. An analytical method is proposed for calculation of the conformational energy gradient of a random molecule.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 23, No. 3, pp. 360–365, May–June 1987.     

Aqueous Capillary Electrophoresis of Peptides Part 2: An Investigation of Quantitative Determinants of Hydration and Solvation Relationships

Summary From the published electrophoretic data for a set of 58 peptides at pH 2.5 we have determined the excess hydration required to correct the deviations of the 31 higher-charged peptides from the Offord plot for the 27 singly-charged peptides. These values of the excess hydration were then used to test physical models by regression analysis. The dominant variable is the total excess positive charge, but the number of excess single positive charges and the number of pairs of positive charges – both at the end and internally – were significant determinants. The effect of acidic side chains was ambiguous throughout the analyses and this was presumed to arise from the ability of carboxy groups to be the sites of additional hydration or to diminish hydration via internal bonding with amino groups. A hydrophobicity index was included in he analysis, but surprisingly this too had little effect. In the last stage of the regressions, we also included coding for secondary structure within the peptides. This increased R² for the plots of the excess hydration versus values calculated from the regression constants (Y) from 0.95 to 0.97. Some solvation relationships were particularly good at modelling the hydration of the smaller, lesser-charged peptides, whilst others excelled in the opposite direction. The final model appeared to deal equally well with both extremes, but is not sufficiently sensitive to allow for all of the variations between peptides. As a result, the excess hydration was modelled very well for many of the peptides (±1–2 waters over the range of excess hydration form 5–276), but poorly for a few (± 100–200%). It was not possible to find another set of peptides that could be independently analysed in a similar fashion and compared. However, the regression constants were applied to an alternative set. Although appearing to fall in a generally reasonable range, various tests of the resultant calculated values indicated that this application was not valid. The second set of peptides were much more hydrophilic and the number of amino acid residues with an extended secondary structure appeared to be a contributing factor.     

Optimized bond lengths and electron densities on atoms in heterosubstituted polyenes

Bond lengths and electron density distribution in the polymethine chain of various heterosubstituted polyenes having carbonyl, cyano, and amino end groups are calculated in geometry-optimized CNDO/2 aproximation. It is shown that the significant alternation of the carbon-carbon bond lengths is largely independent of the nature of the end group, the arrangement of long and short bonds being determined by the form of the polyene. Heterosubstitution causes the electron density to alternate and the alternation amplitude, which decreases towards the middle of the chain, is dependent on the electron-donor properties of the polyene.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 28, No. 4, pp. 313–319, July–August, 1992.     

Stereocontrolled synthesis of A C14-C20 building block for amphotericin B using a novel [2,3] wittig rearrangement

The C1₄-C₂₀ unit 11 of the polyene macrolide antibiotic amphotericin B (1) was synthesized from L-arabinose in 13 steps. The key step 7 → 10 features diastereocontrol through asymmetric induction in a novel [23] Wittig rearrangement.     

Estimation of the hydration of polar groups of α-amino acids by differential scanning calorimetry

The heat capacity of hydration of zwitterions derived from aliphatic amino acids depends linearly on the surface area of the amino acid side radicals accessible to water molecules with the slopeb = 2.35±0.11 J mol^–1 K^–1 Å^–2 at 298 K. The linear correlation between hydration heat capacities of zwitterions of aliphatic amino acids and the corresponding aliphatic alcohols with a coefficient of approximately unity confirms the assumption that hydrophobic hydration does not depend on the nature of the surrounding groups. Using the assumption that the hydration of hydrocarbon radicals is independent of the neighboring groups, theb value has been used to calculate the contributions of polar groups. The contributions of OH, COON, and CONH groups of the side radicals in polar amino acids in the zwitterion form are close to zero; in the case of organic nonionic molecules, these contributions are negative. The increments for polar groups obtained for the zwitterions can be used for the calculation of the heat capacities of proteins and polypeptides incorporating charged amino acid residues. The difference between hydrophilic and hydrophobic hydration mechanisms is manifested not only as different magnitudes and signs of heat capacities and temperature coefficients but also in the fact that the neighboring polar (charged) groups have an effect on hydrophilic hydration but have no effect on hydrophobic hydration.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2237–2242, September, 1996.     

Gel hydration: Obstruction effect in self-diffusion

The extent of hydration of agar has been calculated from the self-diffusion studies of Br^– and I^– ions in agar gel medium. The measured obstruction effect caused by these macromolecules is related to the extent of hydration by Wang's equation. The value of hydration expressed in terms of grams of bound water per gram of anhydrous agar, in presence of NaI and NH₄Br /0.1M/ electrolytes comes out to be about 5.2.     

Intradiffusion coefficients of all species in aqueous gallium perchlorate solutions and solution viscosities at 25°C

Intradiffusion coefficients of all species (cation, anion and solvent) and viscosities have been measured for aqueous solutions of gallium perchlorate in the concentration range 0–2.3 mol-kg^–1 at 25°C. The perchlorate ion intradiffusion measurements were made using³⁶ClO ₄ ^– as the tracer species in diaphragm cell experiments. The development of a method to synthesize³⁶ClO ₄ ^– from³⁶Cl^– by electrolysis is described. The perchlorate intradiffusion coefficients results show a concentration dependence that is very similar to that for D(Cl^–) in corresponding trivalent metal chloride solutions. A simple hydration analysis based on all the transport results estimates a total (effective) cation hydration for gallium within a 0–2 mol-kg^–1 range of 10 (±1.5).     

Some Structural and Thermodynamic Aspects of Solvation of Single Ions. 2. Salt Effects in Aqueous Solutions of 1–1 Electrolytes

The ionic coefficients of the pair interionic interaction in aqueous solutions of 1–1 electrolytes at 298 K were determined from the real activity coefficients of single-charged single ions using the McMillan–Mayer formalism. Analysis of the results of calculations revealed that salt effects are stronger in the case of cations. The weakening of cation hydration (increased negative hydration) and the strengthening of anion hydration (increased positive hydration) enhance the mutual salting of cations and anions. It is shown that the structural effects of hydration produce a strong effect on the interionic interaction in solutions.     

Millimeter spectroscopic study of intermolecular interactions in solutions

The absorption of 5 cm^–1 electromagnetic radiation by aqueous solutions of methyl, ethyl, n-, and isopropyl, sec-, iso-, and tert-butyl, and tert-amyl alcohols and ethylene glycol was measured within their solubility limits in water at 20°C. It was found that the observed nonadditivity of absorption (absorption deficit) is a qualitative measure of hydration of alcohols of two types: hydrophilic and hydrophobic. The possibility of distinguishing these effects by millimeter spectroscopy was demonstrated. Hydrophobic hydration makes the basic contribution to the hydration number of aliphatic alcohols. On the example of solutions of ethanol and tert-butanol, it was shown that hydrophobic hydration decreases with an increase in the temperature of the solution due to intensification of hydrophobic interactions between the hydrocarbon radicals.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1755–1761, August, 1989.     

Electronic structure of long polyene ions

The ionization potentials, densities of the one-electron states, and distribution of the charge have been calculated in the -electronic approximation for linear polyene ions containing up to 100 carbon atoms. The role of the electrostatic interaction in these systems has been discussed.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 4, pp. 393–398, July–August, 1989.     

Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes.

BACKGROUND: The polyene macrolide amphotericin B is produced by Streptomyces nodosus ATCC14899. Amphotericin B is a potent antifungal antibiotic and has activity against some viruses, protozoans and prions. Treatment of systemic fungal infections with amphotericin B is complicated by its low water-solubility and side effects which include severe nephrotoxicity. Analogues with improved properties could be generated by manipulating amphotericin biosynthetic genes in S. nodosus. RESULTS: A large polyketide synthase gene cluster was cloned from total cellular DNA of S. nodosus. Nucleotide sequence analysis of 113193 bp of this region revealed six large polyketide synthase genes as well as genes for two cytochrome P450 enzymes, two ABC transporter proteins, and genes involved in biosynthesis and attachment of mycosamine. Phage KC515-mediated gene disruption was used to show that this region is involved in amphotericin production. CONCLUSIONS: The availability of these genes and the development of a method for gene disruption and replacement in S. nodosus should allow production of novel amphotericins. A panel of analogues could lead to identification of derivatives with increased solubility, improved biological activity and reduced toxicity.     

Molecular–Continuum Model for Calculating Chemical Hydration Enthalpy of the Cyanide Ion

Structures of hydrate complexes (H₂O) _x CN^–(H₂O) _y , where x + y = 1–5 are optimized by the density functional method in the B3LYP version. It is shown that the nearest hydration sphere of the cyanide ion comprises four water molecules directly linked to the ion by hydrogen bonds. The chemical enthalpy of the hydration of the cyanide ion is calculated in the reactive-field continuum models (PCM and SCIPCM) and in other nonelectrostatic interactions. The calculation takes into account the electrostatic interaction between the hydrate complex and the solvent's dielectric surrounding. Calculation results are in good agreement with experiment.     

Distortions in quasi-one-dimensional polyconjugated systems

The Hückel and Lennard-Jones approximation is used to show that structural distortions with bond-length alternation in the chains are impossible because of the high rigidity of the core in a conjugated system for any long polyconjugated system of polyacene type that can be represented as polyene chains linked together.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 23, No. 3, pp. 350–352, May–June, 1987.     

Electronic structure of long polyene chains with consideration of long-range electrostatic effects and the influence of the terminal groups

The role of long-range interactions has been considered in the case of polyene chains containing up to 100 CH groups with consideration of the interaction of the electrons with the Pariser-Parr-Pople Hamiltonian in the self-consistent-field approximation (by the Hartree-Fock and spin-unrestricted Hartree-Fock methods), and the energies of the first optical excitation, the densities of the one-electron states, and the distribution of the bond orders along the chain have been found. The question of the existence of states with spin-density waves and bond-order waves in a linear polyene has been investigated.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 22, No. 2, pp. 146–153, March–April, 1986.We thank A. E. Belinskii for participating in obtaining some of the results on the influence of the long-range electrostatic interactions on the electronic structure of cyclic polyenes and A. L. Chugreev for participating in continual discussions.     

State of the hydroxide ion in water and aqueous solutions

Conclusion Analysis of these experimental facts leads to the conclusion that in water and aqueous solutions of alkali metal hydroxides it is extremely probable that the hydroxide ion exists in the form H₃O₂ ^–. The marked displacement of the extrapolated chemical shift of the proton of the H₃O₂ ^– ion towards weak fields and the displacement of the frequency of the bending vibrations of the OH bond towards higher frequencies for hydroxide solutions indicate strong hydrogen bonding between the OH^– ion and the H₂O molecule. The comparatively low heat of hydration of the OH^– ion (111 cal/mole) compared with the heat of hydration of the H₊ ion (276 cal/mole) cannot, as has been shown, serve as proof that there is no strong electrostatic bond between the OH^– ion and a water molecule. All the heat of hydration is used up in the formation of this bond; this can be regarded as additional confirmation of the hydrophobic nature of the ion produced. The experimental data on the absolute value of the chemical shift of the proton of the H₃O₂ ^– ion indicate the important role played by the excited state of the proton in this complex. This conclusion agrees with the spectroscopic data.M. V. Lomonosov Moscow State University. Translated from Zhurnal Strukturnoi Khimii, Vol. 12, No. 6, pp. 969–974, November–December, 1971.     

Synthesis of 28-F-amphotericin B methyl ester

A fluorinated amphotericin B (AmB) derivative, 28-¹⁹F-AmB methyl ester (3), labeled at the polyene moiety, was synthesized by combining chemical synthesis with degradation of a natural product via cross-coupling reactions and macrolactonization. The fluorinated derivative 3 showed antifungal activity similar to that of AmB, and is expected to be a powerful tool for NMR-based investigation of the mechanism of ion-channel formation.     

Lower critical solution temperature and hydrophobic hydration in aqueous polymer solutions

Phase diagrams of aqueous solutions of poly(N-vinyl caprolactam) (PVCL), N-vinyl caprolactam copolymer with vinylamine (3.8 mol%) (CP(VCL-VA)), and poly(N-vinyl propylacetamide) (PVPA) were shown to be binodal curves with lower critical solution temperatures (LCST) in the range 304–313.5 K and critical concentrations in the range of 0.02–0.08 polymer weight fraction. Aqueous solutions of N-vinyl caprolactam copolymer with N-vinyl pyrrolidone (80 mol%) (CP(VCL-VP)) remained homogeneous in the entire region of the liquid state of water. The enthalpy of mixing with water of PVPA and CP(VCL-VP) was negative and the curve was concave over the entire range of composition at 298 and 308 K. The excessive heat capacity and partial heat capacity at infinite dilution of PVPA were positive, proving the hydrophobic character of hydration of this polymer. In contrast, these parameters were negative for CP(VCL-VP), revealing hydrophilic hydration. Hydrophilic hydration was predominant in solutions which were homogeneous over a wide temperature range, whereas hydrophobic hydration predominated in solution of polymers with LCST.     

Stability of spherical and rod-like micelles of ionic surfactants,in relation to their counterion binding and modes of hydration

Aqueous salt solutions of ionic surfactants in both spherical and rod-like micelles have been treated on the basis of a statistical thermodynamic theory, and the double logarithmic relationship between micelle molecular weight and ionic strength is derived for each micelle. Counterion binding on both micelles are assumed to occur specifically, and their degrees of dissociation are related to the slopes of the linear double logarithmic relations. It is found from the relationship observed for typical surfactants that the effective charge of spherical micelles is 29±4. The degree of dissociation of rod-like micelles of these surfactants is primarily determined by the counterion species, yielding values 0.8 for Na⁺, 0.4–0.6 for Cl^– and 0.2–0.3 for Br^–. Hydrophilic hydration of both micelles can be evaluated from the intercepts of the linear relations. Hydrophilic hydration acts repulsively in spherical micelles, while it is attractive or much less repulsive in rod-like micelles.