Isolation and X-ray structure analysis of citreohybridonol from marine-derived Penicillium atrovenetum

The anti-neuroinflammatory meroterpenoid citreohybridonol was isolated for the first time from a sponge-derived fungus Penicillium atrovenetum. In this study, in addition to isolation and structure featuring, its unambiguous absolute configuration was determined exclusively by single crystal X-ray diffraction. The C-17-keto tautomer was clearly observed in X-ray analysis. The substance crystallises in the monoclinic space group P2₁ with a = 10.7496(5) Å, b = 14.3286(7) Å, c = 17.4909(8) Å, β = 103.235(2)°, V = 2622.5(2) Å³, Z = 2, D_calcd = 1.280 g/cm³. The chirality of the asymmetric carbon atoms was as follows: C3 (S), C5 (R), C6 (S), C8 (S), C9 (R), C10 (R), C13 (R), C14 (R).     

Rapid Estimation of Octanol–Water Partition Coefficient for Triazole Fungicides by MEKC with Sodium Deoxycholate as Surfactant

A rapid estimation of octanol–water partition coefficient (log P _ow) was developed for triazole fungicides by micellar electrokinetic chromatography (MEKC). Five standard compounds with known log P _ow values from 2.9 to 4.3 (cyproconazole, bromuconazole, epoxiconazole, bitertanol and difenoconazole) were used for constructing the calibration curve of the log P _ow against the MEKC retention factor, log k. A linear relationship was achieved between log P _ow and log k, in the MEKC system containing 40 mM sodium deoxycholate (SDC) and 4 mM borate buffer at pH 9.3, with a correlation of determination, r ² = 0.9905. The log P _ow values of four test compounds of triazole fungicides (triadimenol, myclobutanil, propiconazole and penconazole) were calculated based on the log k values measured by MEKC and the slope and intercept of the calibration curve. This MEKC method can give good estimation of the log P _ow of the four test compounds of triazole fungicides with the differences between the literature log P _ow values and estimated log P _ow from the MEKC method were from 0.15 to 0.23 log units.     

Impacts of medium,substituents, and specific interactions with water on hydration of carbonyl compounds

Theoretical study on hydration of carbonyl compounds has been done at B3LYP/6-31++G** and MP2/6-31++G** levels. The variations in ΔG _hyd and hydration constants are explored in terms of medium effect, substituent effect, and hydrogen bonding abilities of carbonyl compounds and their hydrated products. The dielectric of medium decreases the ΔG _hyd values thereby favoring the process. The presence of electron-releasing substituents at the carbonyl carbon disfavors the hydration process, while that of electron-withdrawing substituents favor the process. Hydrogen bonding interactions stabilize the product to a larger extent than the carbonyl molecules, thereby favoring the hydration process. Linear correlation between the calculated log K _hyd values and the experimental values is seen in case of specific interactions with water (R = 0.976) than in the case without those interactions (R = 0.955).     

Inclusion complexes of cyclodextrins with 4-amino-1,8-naphthalimides (part 2)

Fluorescence spectroscopy was used to characterize inclusion compounds between 4-amino-1,8-naphthalimides (ANI) derivatives and different cyclodextrins (CDs). The ANI derivatives employed were N-(12-aminododecyl)-4-amino-1,8-naphthalimide (mono-C₁₂ANI) and N,N′-(1,12-dodecanediyl)bis-4-amino-1,8-naphthalimide (bis-C₁₂ANI). The CDs used here were α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD and HP-γ-CD. The presence of CDs resulted in pronounced blue-shifts in the emission spectra of the ANI derivatives, with increases in emission intensity. This behavior was parallel to that observed for the dyes in apolar solvents, indicating that inclusion complexes were formed between the ANI and the CDs. Mono-C₁₂ANI formed inclusion complexes of 1:1 stoichiometry with all the CDs studied. Complexes with the larger CDs (HP-β-CD, HP-γ-CD and γ-CD) were formed by inclusion of the chromophoric ANI ring system, whereas the smaller CDs (α-CD, HP-α-CD and β-CD) formed complexes with mono-C₁₂ANI by inclusion of the dodecyl chain. Bis-C₁₂ANI formed inclusion complexes of 1:2 stoichiometry with HP-β-CD, HP-γ-CD and γ-CD, but did not form inclusion complexes with α-CD, HP-α-CD and β-CD. The data were treated in the case of the large CDs using a Benesi-Hildebrand like equation, giving the following equilibrium constants: mono-C₁₂ANI:HP-β-CD (K ₁₁ = 50 M^?1), mono-C₁₂ANI:HP-γ-CD (K ₁₁ = 180 M^?1), bis-C₁₂ANI:HP-β-CD (K ₁₂ = 146 M^?2), bis-C₁₂ANI:HP-γ-CD (K ₁₂ = 280 M^?2).     

ClogPalk: a method for predicting alkane/water partition coefficient

Alkane/water partition coefficients (P_alk) are less familiar to the molecular design community than their 1-octanol/water equivalents and access to both data and prediction tools is much more limited. A method for predicting alkane/water partition coefficient from molecular structure is introduced. The basis for the ClogP_alk model is the strong (R² = 0.987) relationship between alkane/water partition coefficient and molecular surface area (MSA) that was observed for saturated hydrocarbons. The model treats a molecule as a perturbation of a saturated hydrocarbon molecule with the same MSA and uses increments defined for functional groups to quantify the extent to which logP_alk is perturbed by the introduction each functional group. Interactions between functional groups, such as intramolecular hydrogen bonds are also parameterized within a perturbation framework. The functional groups and interactions between them are specified substructurally in a transparent and reproducible manner using SMARTS notation. The ClogP_alk model was parameterized using data measured for structurally prototypical compounds that dominate the literature on alkane/water partition coefficients and then validated using an external test set of 100 alkane/water logP measurements, the majority of which were for drugs.     

Crystal and molecular structure of β-cyclodextrin inclusion complex with succinic acid

The crystal complex of β-cyclodextrin with succinic acid, intermediate product of hydrolysis reaction of succinic anhydride in the presence of β-cyclodextrin, was isolated and studied by X-ray analysis (monoclinic, space group P2₁, a = 15.1977(7) Å, b = 10.1763(5) Å, c = 20.6943(6) Å, β = 109.239(4)°, V = 3021.8(2) Å³, Z = 2, R ₁ = 0.0359, wR ₂ = 0.0947). It was proved that β-cyclodextrin and succinic acid form an inclusion complex, which exists in crystal state as a heptahydrate. The molecule of succinic acid is fully included in the β-cyclodextrin cavity with its carboxyl groups accessible for water molecules. Water molecules located at borders of cavity rims and in interstices between molecules of β-cyclodextrin participate in formation of intermolecular hydrogen bonds. The overall structure does not contain disordered fragments. The crystal conformation of succinic acid corresponds to one of possible conformers of the molecule in vacuo and is almost not disturbed by intermolecular interactions in crystal. Based on the analysis of structural features of the crystal conformation of succinic acid and character of its location in the β-cyclodextrin cavity, it was suggested that hydrolysis of succinic anhydride via ring opening and formation of succinic acid is mediated by cyclodextrin microenvironment and it likely occurs near the narrow rim of the macrocycle cavity.     

Thermal properties of mixed-ligand magnesium complexes with beta-diketonates and diamimes as potential MOCVD precursors

The series of adducts of magnesium beta-diketonates with diamimes namely Mg(thd)₂(tmeda) 1 and four new complexes Mg(thd)₂(tmpda) 2, Mg(thd)₂(pda) 3, Mg(ptac)₂(tmeda) 4, Mg(tfac)₂(tmeda) 5 [beta-diketonates = R₁C(O)CHC(O)R₂: thd (R₁ = R₂ =  ^t Bu), ptac (R₁ =  ^t Bu, R₂ = CF₃), tfac (R₁ = Me, R₂ = CF₃); diamines = R₂N(CH₂) _n NR₂: tmeda (n = 2, R = Me), tmpda (n = 3, R = Me), pda (n = 3, R = H)] were synthesized in order to investigate the influence of both ligand types on the thermochemical properties of these compounds. The thermal behavior of the complexes in the condensed phase was investigated by thermogravimetry and differential scanning calorimetry; the thermodynamic parameters of phase transitions were determined. The saturated vapor pressure of solid complexes Mg(thd)₂(tmeda) and Mg(tfac)₂(tmeda) were measured by the transmission method giving the enthalpies and entropies of sublimation processes. The reliable thermodynamic data for compound Mg(thd)₂(tmeda) were obtained with the assistance of X-ray diffraction and the static method of saturated and unsaturated vapor pressure measurements.     

Development and evaluation of a 166holmium labelled porphyrin complex as a possible therapeutic agent

Porphyrins are interesting derivatives with low toxicity, tumor avidity and rapid wash-out suggested as potential radiopharmaceuticals in radiolabeled form. In this work, [¹⁶⁶Ho] labeled 5,10,15,20-tetrakis(phenyl) porphyrin ([¹⁶⁶Ho]-TPP) was prepared using [¹⁶⁶Ho]HoCl₃ and 5,10,15,20-tetrakis(phenyl)porphyrin (H₂TPP) for 12 h at 50 °C (radiochemical purity: >95 ± 2 % ITLC, >99 ± 0.5 % HPLC, specific activity: 0.9–1.1 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 2.01). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT. A detailed comparative pharmacokinetic study performed for ¹⁶⁶Ho cation and [¹⁶⁶Ho]-TPP performed up to 24 h. The complex is mostly washed out from the circulation through kidneys and in less extends from the liver. The kidney:blood, kidney:liver and kidney:muscle ratios 4 h post injection were 14, 3.6 and 7.38 respectively.     

The SAMPL5 challenge for embedded-cluster integral equation theory: solvation free energies,aqueous p<Emphasis Type="Italic">K</Emphasis><Subscript>a</Subscript>, and cyclohexane–water log <Emphasis Type="Italic">D</Emphasis>

We predict cyclohexane–water distribution coefficients (log D _7.4) for drug-like molecules taken from the SAMPL5 blind prediction challenge by the “embedded cluster reference interaction site model” (EC-RISM) integral equation theory. This task involves the coupled problem of predicting both partition coefficients (log P) of neutral species between the solvents and aqueous acidity constants (pK _a) in order to account for a change of protonation states. The first issue is addressed by calibrating an EC-RISM-based model for solvation free energies derived from the “Minnesota Solvation Database” (MNSOL) for both water and cyclohexane utilizing a correction based on the partial molar volume, yielding a root mean square error (RMSE) of 2.4 kcal mol^?1 for water and 0.8–0.9 kcal mol^?1 for cyclohexane depending on the parametrization. The second one is treated by employing on one hand an empirical pK _a model (MoKa) and, on the other hand, an EC-RISM-derived regression of published acidity constants (RMSE of 1.5 for a single model covering acids and bases). In total, at most 8 adjustable parameters are necessary (2–3 for each solvent and two for the pK _a) for training solvation and acidity models. Applying the final models to the log D _7.4 dataset corresponds to evaluating an independent test set comprising other, composite observables, yielding, for different cyclohexane parametrizations, 2.0–2.1 for the RMSE with the first and 2.2–2.8 with the combined first and second SAMPL5 data set batches. Notably, a pure log P model (assuming neutral species only) performs statistically similarly for these particular compounds. The nature of the approximations and possible perspectives for future developments are discussed.     

Affinity capillary electrophoretic study of K+/Na+ selectivity of hexaarylbenzene-based polyaromatic receptor

Affinity capillary electrophoretic (ACE) study has proved the selectivity of hexaarylbenzene-based polyaromatic receptor (R) for K⁺ ion over Na⁺ ion. The apparent binding constants of the R complexes with K⁺ and Na⁺ ions were determined from the dependence of effective electrophoretic mobility of R on the concentration of the above alkali metal ions in the background electrolyte using a non-linear regression analysis. The apparent binding constants (K_b) of the K-R⁺ and Na–R⁺ complexes in methanolic medium were evaluated as log K_b = 3.20 ± 0.22 for the K–R⁺ complex, and log K_b??0.7 for the Na–R⁺ complex.     

Bis-thiourea macrocycles incorporating fused [n]polynorbornanes: binding of flexible versus rigid dicarboxylates

Two macrocyclic bis-thiourea hosts 5 and 6 were constructed and their interactions with two dicarboxylates of similar size (pimelate = flexible and terephthalate = rigid) were evaluated using ¹H NMR titration techniques. In contrast to previous work with thiourea functionalised [n]polynorbornanes (where a notable increase in H:G affinity was noted for the rigid guest), the new macrocyclic hosts, in particular host 6, bind pimelate more strongly than terephthalate (for 6 binding pimelate log K_a = 4.7, terephthalate log K_a = 3.7). A binding arrangement in which the flexible dicarboxylate is ‘perched’ above the macrocycle is proposed to justify these results.     

Correlation of the Solubilizing Abilities of 1-Butyl-1-methyl-pyrrolidinium Tris(pentafluoroethyl)trifluorophosphate, 1-Butyl-1-methylpyrrolidinium Triflate and 1-Methoxyethyl-1-methylmorpholinium Tris(pentafluoroethyl)trifluorophosphate

Chromatographic retention data were measured for a wide range of organic solutes on 1-butyl-1-methylpyrolidinium tris(pentafluoroethyl)trifluorophosphate ([BMPyrr]⁺[FAP]^?), 1-butyl-1-methylpyrrolidinium triflate, ([BMPyrr]⁺[Trif]^?), and 1-methoxyethyl-1-methylmorpholinium tris(pentafluoroethyl)trifluorophosphate, ([MeoeMMorp]⁺[FAP]^?), stationary phases at (323, 353 and 383) K. The measured retention factors were combined with published infinite dilution activity coefficient and gas-to-water partition coefficient data to yield gas-to-anhydrous ionic liquid (IL) and water-to-anhydrous IL partition coefficients. The three sets of partition coefficients were analyzed using the Abraham model. The derived Abraham model correlations describe the observed gas-to-IL (log₁₀ K) and water-to-IL (log₁₀ P) partition coefficient data to within average standard deviations of about 0.11 and 0.15 log₁₀ units, respectively.     

Interaction between cucurbit[8]uril and viologen derivatives

The interaction between cucurbit[8]uril (Q[8]) and a series of symmetric viologen derivatives having aliphatic substituents of variable length [N,N′-dialkyl-4,4′-bipyridinium dianions; alkyl = CH₃(CH₂) _n –, n = 0 (MV²⁺), 1 (EV²⁺), 2 (PV²⁺), 3 (BV²⁺), 4 (FV²⁺), 5 (HV²⁺) or 6 (SV²⁺); BPY²⁺ = diprotonated 4,4-bipyridine], determined by ¹H NMR and electronic absorption spectroscopy methods, is described. Some different binding models were observed in this work when compared to the interactions between cucurbit[7]uril (Q[7]) and these guests. The experimental results revealed that the binding site of the guests by Q[8] depended strongly on the length of the aliphatic substituents on the 4,4′-bipyridinium nucleus. While a 1:2 complex was observed for Q[8]-BPY²⁺ under acidic conditions, a 1:1 complex was formed for Q[8]-viologen derivatives with chains shorter than four carbon atoms. However, multiple Q[8] molecules could be threaded on the longer-chain FV²⁺, HV²⁺ or SV²⁺ molecules to form 2:1 and even possibly 3:1 complexes.     

Hydrogen Bonding and Solvent Effects on Complexation of Alkali Metal Cations by Lower Rim Calix[4]arene Tetra(O-[N-acetyl-D-phenylglycine methyl ester]) Derivative

Complexation of alkali metal cations with 5,11,17,23-tetra-tert-butyl-26,28,25,27-tetrakis(O-methyl-D-α-phenylglycylcarbonylmethoxy)calix[4]arene (L) was studied by means of spectrophotometric, conductometric and potentiometric titrations at 25 °C. The solvent effect on the binding ability of L was examined by using two solvents with different affinities for hydrogen bonding, viz. methanol and acetonitrile. Despite the presence of intramolecular NH···O=C hydrogen bonds in L, which need to be disrupted to allow metal ion binding, this calix[4]arene amino acid derivative was shown to be an efficient binder for smaller Li⁺ and Na⁺ cations in acetonitrile (lg K _LiL  > 5, lg K _NaL  = 7.66), moderately efficient for K⁺ (lg K _KL  = 4.62), whereas larger Rb⁺ and Cs⁺ did not fit in its hydrophilic cavity. The complex stabilities in methanol were significantly lower (lg K _NaL  =  4.45, lg K _KL  = 2.48). That could be explained by different solvation of the cations and by competition between the cations and methanol molecules (via hydrogen bonds) for amide carbonyl oxygens. The influence of cation solvation on complex stability was most pronounced in the case of Li⁺ for which, contrary to the quite stable LiL ⁺ complex in acetonitrile, no complexation was observed in methanol under the conditions used.     

Dissolved air flotation for treating wastewater of the nuclear industry: preliminary results

Preliminary testing of dissolved air flotation (DAF) for wastewater treatment is presented. A combined coagulation-flocculation/DAF column system is used to remove oil and ⁶⁰Co from nuclear industry wastewater. In this work, operational conditions and coagulant/flocculant concentrations are optimized by varying pH. Determinations of air-solids ratio (G/S), retention time (θ), pressure (P), volume of depressurized air–water mixture (V), turbidity and ⁶⁰Co concentrations are reported. The effect of the treatment on the efficiency of separation of oily residues is also discussed. The results establish that the coagulant/flocculant system, formed by a modified polyamine (25 mgL^?1) and a slightly cationic polyacrylamide (1.5 mgL^?1), under specific operational conditions (pH = 7, mixing intensity Im₁ = 300 s^?1 and Im₂ = 30 s^?1), allowed the destabilization of colloidal matter, resulting in resistant flocs. It was concluded that by using G/S = 0.3, θ = 15 min, P = 620 kPa and V = 0.0012 m³, the greatest percentage removals of oil, turbidity, total cobalt and ⁶⁰Co were obtained. These preliminary results then show that dissolved air flotation represents a good alternative for treatment of nuclear industry wastewater contaminated with radionuclides.