Ozren Jović

A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers

A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-, VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE.

Spectroscopic and Chemometric Analysis of Binary and Ternary Edible Oil Mixtures: Qualitative and Quantitative Study.

The aim of this study was to investigate the feasibility of FTIR-ATR spectroscopy coupled with the multivariate numerical methodology for qualitative and quantitative analysis of binary and ternary edible oil mixtures. Four pure oils (extra virgin olive oil, high oleic sunflower oil, rapeseed oil, and sunflower oil), as well as their 54 binary and 108 ternary mixtures, were analyzed using FTIR-ATR spectroscopy in combination with principal component and discriminant analysis, partial least-squares, and principal component regression. It was found that the composition of all 166 samples can be excellently represented using only the first three principal components describing 98.29% of total variance in the selected spectral range (3035-2989, 1170-1140, 1120-1100, 1093-1047, and 930-890 cm(-1)). Factor scores in 3D space spanned by these three principal components form a tetrahedral-like arrangement: pure oils being at the vertices, binary mixtures at the edges, and ternary mixtures on the faces of a tetrahedron. To confirm the validity of results, we applied several cross-validation methods. Quantitative analysis was performed by minimization of root-mean-square error of cross-validation values regarding the spectral range, derivative order, and choice of method (partial least-squares or principal component regression), which resulted in excellent predictions for test sets (R(2) > 0.99 in all cases). Additionally, experimentally more demanding gas chromatography analysis of fatty acid content was carried out for all specimens, confirming the results obtained by FTIR-ATR coupled with principal component analysis. However, FTIR-ATR provided a considerably better model for prediction of mixture composition than gas chromatography, especially for high oleic sunflower oil.

Structure-Property Relationship of Quinuclidinium Surfactants – Towards Multifunctional Biologically Active Molecules

Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical properties represents a good starting point for further biological research.

Interval ridge regression (iRR) as a fast and robust method for quantitative prediction and variable selection applied to edible oil adulteration.

A novel quantitative prediction and variable selection method called interval ridge regression (iRR) is studied in this work. The method is performed on six data sets of FTIR, two data sets of UV-vis and one data set of DSC. The obtained results show that models built with ridge regression on optimal variables selected with iRR significantly outperfom models built with ridge regression on all variables in both calibration (6 out of 9 cases) and validation (2 out of 9 cases). In this study, iRR is also compared with interval partial least squares regression (iPLS). iRR outperfomed iPLS in validation (insignificantly in 6 out of 9 cases and significantly in one out of 9 cases for p<0.05). Also, iRR can be a fast alternative to iPLS, especially in case of unknown degree of complexity of analyzed system, i.e. if upper limit of number of latent variables is not easily estimated for iPLS. Adulteration of hempseed (H) oil, a well known health beneficial nutrient, is studied in this work by mixing it with cheap and widely used oils such as soybean (So) oil, rapeseed (R) oil and sunflower (Su) oil. Binary mixture sets of hempseed oil with these three oils (HSo, HR and HSu) and a ternary mixture set of H oil, R oil and Su oil (HRSu) were considered. The obtained accuracy indicates that using iRR on FTIR and UV-vis data, each particular oil can be very successfully quantified (in all 8 cases RMSEP<1.2%). This means that FTIR-ATR coupled with iRR can very rapidly and effectively determine the level of adulteration in the adulterated hempseed oil (R(2)>0.99).

Durbin-Watson partial least-squares regression applied to MIR data on adulteration with edible oils of different origins

A novel method for quantitative prediction and variable-selection on spectroscopic data, called Durbin-Watson partial least-squares regression (dwPLS), is proposed in this paper. The idea is to inspect serial correlation in infrared data that is known to consist of highly correlated neighbouring variables. The method selects only those variables whose intervals have a lower Durbin-Watson statistic (dw) than a certain optimal cutoff. For each interval, dw is calculated on a vector of regression coefficients. Adulteration of cold-pressed linseed oil (L), a well-known nutrient beneficial to health, is studied in this work by its being mixed with cheaper oils: rapeseed oil (R), sesame oil (Se) and sunflower oil (Su). The samples for each botanical origin of oil vary with respect to producer, content and geographic origin. The results obtained indicate that MIR-ATR, combined with dwPLS could be implemented to quantitative determination of edible-oil adulteration.

Using synergy of experimental and computational techniques to solve monomer–trimer dilemma

An example of commercially available product, 2- (methylideneamino)acetonitrile (MAAN). This paper will address problems in discerning monomer– polymer ambiguity in organic compounds. Reliable three-step analysis of organic polymers will be proposed using the synergy of computational [density functional theory (DFT)] and experimental [infrared spectroscopy (IR) ; X-ray powder diffraction (XRPD)] techniques. First, possible conformations of monomeric and trimeric MAAN were calculated using stochastic search and DFT. Second, identification of the commercial sample was performed by comparing the measured IR spectrum with those calculated for monomer and trimer. Third, the examination of sample purity and structural analysis were carried out using XRPD data.

Maceration of Extra Virgin Olive Oil with Common Aromatic Plants Using Ultrasound-Assisted Extraction: An UV-Vis Spectroscopic Investigation

Rosemary (Rosmarinus officinalis), garden sage (Salvia officinalis), summer savory (Satureja hortensis), laurel (Laurus nobilis), and other aromatic plants were put in olive oil and exposed to ultrasounds for different duration. Filtrated oils were dissolved in cyclohexane, and UV-Vis measurements were carried out. Absorbance values corresponding to chlorophylls, carotenoids, flavonoids (370 nm), and polyphenols (around 300 nm) were measured. In addition, for some samples, total phenols were determined using Folin-Denis reagent and compared with the similar maceration procedure in water solvent (instead of olive oil). Maceration without ultrasound in olive oil for each plant was also compared with ultrasound-assisted extraction. The results show that significant amount of aromatic content can be extracted in olive oil by applying ultrasounds for only few minutes, especially for Salvia officinalis powder. The use of UV-Vis measurements is simple but enough to examine the extent of phenol content extraction through such maceration procedure.

CCDC 1522903: Experimental Crystal Structure Determination

Related Article: Neven Smrecki, Vladimir Stilinovic, Ozren Jovic, Boris-Marko Kukovec, Zora Popovic|2017|Inorg.Chim.Acta|462|57|doi:10.1016/j.ica.2017.03.011

FTIR‐ATR adulteration study of hempseed oil of different geographic origins

Adulteration of hempseed (H) oil, a well‐known health beneficial nutrient, is studied in this work by mixing it with cheap and widely used oils such as rapeseed (R) oil and sesame (Se) and sunflower (Su) oil. Many samples of different geographic origins were taken into account. Binary mixture sets of hempseed oil with these 3 oils (HR, HSe, and HSu) were considered. FTIR spectra of pure oils and their mixtures were recorded, and quantitative analyses were performed using partial least squares regression (PLS) and first‐break forward interval PLS methods (FB‐FiPLS). The obtained results show that each particular oil can be very successfully quantified (R2(val) > 0.995, RMSECV 0.9%–2.9%, RMSEP 1.0%–3.2%). This means that FTIR coupled with multivariate methods can rapidly and effectively determine the level of adulteration in the adulterated hempseed oil for these studied and frequently used adulterant oils. Also, the relevant variables selected by FB‐FiPLS could be used for verification of hempseed oil adulteration.