Quantitative structure-retention relationship study of arylpiperazines by liquid chromatography and multivariate chemometric methods

Cilj ove disertacije bilo je sistematsko proučavanje hromatografskog ponašanja serije novosintetisanih arilpiperazina u uslovima planarne hromatografije, procena retencionih podataka na osnovu multivarijantnih statističkih metoda i utvrđivanje veze između retencionih karakteristika i fizičko-hemijskih parametara ispitivanih molekula. Različiti reverzno-fazni hromatografski sistemi uspešno su primenjeni za razdvajanje ispitivanih arilpiperazina. Definisane su međumolekulske interakcije koje upravljaju retencionim ponašanjem ispitivanih supstanci. To su pre svega hidrofobne, elektrostatičke i interakcije koje uključuju građenje vodoničnih veza. Ponašanje arilpiperazina u primenjenim hromatografskim uslovima u saglasnosti je sa njihovim strukturnim svojstvima, kao i sa interakcijama za koje je utvrđeno da se uspostavljaju kada se ligand koji pokazuje afinitet prema dopaminskim D2 i serotoninskim 5-HT1A receptorima približi aktivnom centru receptora. Lipofilnost ispitivanih arilpiperazina određena je pomoću četiri hromatografska deskriptora, RM 0, b, C0 i PC1. Na osnovu statističkih parametara linearne zavisnosti pomenutih deskriptora i izračunatih logP vrednosti, utvrđeno je da varijabla koja direktno opisuje raspodelu supstanci između stacionarne i mobilne faze, kao što je parameter RM 0, pouzdanije određuje lipofilnost ispitivanih arilpiperazina od parametra koji je proporcionalan hidrofobnoj površini molekula (b) ili interpolisane veličine koja obuhvata sve hromatografske podatke jednog sistema (PC1). Analiza glavnih komponenata i klasterska analiza kao i višestruka linearna regresija, regresija metodom delimičnih-najmanjih kvadrata i regresija glavnih komponenata primenjene su za identifikaciju molekulskih deskriptora koji na najbolji način opisuju ponašanje ispitivanih jedinjenja u hromatografskom sistemu, kao i za kvantifikaciju njihovog uticaja, a u cilju dobijanja matematičkih modela koji bi mogli da predvide hromatografsko ponašanje, odnosno lipofilnost novih srodnih molekula. Statistički parametri potvrđuju da su predloženi modeli statistički značajni i uporedivi. Molekulski deskriptori uključeni u konačne modele su slične prirode i njihov uticaj je približno jednak. Potvrđeno je da je hromatografsko ponašanje molekula određeno dvema komponentama, veličinom molekula i sposobnošću građenja vodoničnih veza. Usled većeg uticaja parametara rastvorljivosti na RM 0 vrednosti, pretpostavljeno je da je u posmatranom hromatografskom sistemu particija dominantni mehanizam razdvajanja u odnosu na adsorpciju. Prediktivna svojstva dobijenih modela potvrđuju mogućnost njihovog korišćenja za predviđanje lipofilnosti novih, strukturno sličnih jedinjenja, kao i za razumevanje njihovog hromatografskog ponašanja.The main goal of this PhD thesis was a systematic study of the retention of the newly synthesized arylpiperazines in planar chromatographic conditions, evaluation of the retention data by multivariate statistical methods and determination of the possible relationship between the retention characteristics and the physicochemical parameters of the investigated arylpiperazines. Different reversed-phase chromatographic systems are successfully applied for the separation of the investigated arylpiperazines. Hydrophobic, electrostatic and hydrogen bond interactions were defined as the most important molecular interactions govern the retention process. The results obtained are in accordance with the structural properties of the investigated compounds and moreover with the interactions established for their binding affinity at the dopamine D2 and serotonin 5-HT1A receptors. Four chromatographic descriptors, RM 0, b, C0 i PC1 are used for assessing the lipophilicity of unknown solutes. These parameters were compared with calculated logP values, and statistical quality of these dependences shows that variables describing directly solute partitioning between stationary and mobile phase, such as RM 0, are more suitable for lipophilicity estimation than parameters proportional to the molecular hydrophobic surface area (b), or interpolated quantity which combines all chromatographic data in one single feature (PC1). Principal component analysis and cluster analysis followed by multiple linear regression, partial least square regression and principal component regression, were performed to identify the molecular descriptors that best describe the chromatographic behavior of the investigated compounds, and to quantify their influences, in order to create a model that could be able to predict chromatographic behavior or lipophilicity of a newly synthesized molecules. The statistical parameters revealed that the models are statistically significant and their statistical results are comparable. The descriptors included in the final models of these three methods are of similar nature and significance. All models confirm the importance of the size of the molecule and hydrogen bonding interactions in assessment of their chromatographic behavior. According to larger influence of the solubility parameters on RM 0 values, it was concluded that partition was the dominant separation mechanism in studied chromatographic systems. Predictive ability of the obtained models and equations based on the physically meaningful parameters allows an estimation of lipophilicity for similar compounds and understanding of their chromatographic behavior

Supplementary data for the article: Stefanović, V.; Trifković, J.; Mutić, J.; Tešić, Ž. Metal Accumulation Capacity of Parasol Mushroom (Macrolepiota Procera) from Rasina Region (Serbia). Environ. Sci. Pollut. Res. 2016, 23 (13), 13178–13190. https://doi.org/10.1007/s11356-016-6486-7

Supplementary material for: [https://doi.org/10.1007/s11356-016-6486-7]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2271

Supplementary material for the article: Stefanović, V.; Trifković, J.; Djurdjić, S.; Vukojević, V.; Tešić, Ž.; Mutić, J. Study of Silver, Selenium and Arsenic Concentration in Wild Edible Mushroom Macrolepiota Procera, Health Benefit and Risk. Environmental Science and Pollution Research 2016, 23 (21), 22084–22098. https://doi.org/10.1007/s11356-016-7450-2

Supplementary material for: [https://doi.org/10.1007/s11356-016-7450-2]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2348

Impact of Vial Bubble on the Accuracy of Positions in the GNSS-RTK Mode

The use of the GNSS devices in the RTK mode involves taking a vertical position using a circular spirit vial bubble located on the rod. Since the market of geodetic instruments, accessories and software is growing, the authors of this paper performed measurements with the GNSS devices in the RTK mode to determine and demonstrate the impact of the position of the central vial bubble (level) on coordinate accuracy. Measurements were performed on the same rod in the RTK permanent stations network. Instruments of different manufacturers and generations were used in the experiment. Newer generations of the GNSS devices are equipped with special sensors for measuring the inclination of the receiver and eliminating this error. Devices that do not have a sensor give measuring coordinates that are loaded with error. The error is random and cannot be measured. The subject of the analysis of this paper is the magnitude and impact of the error caused by the non-verticality of the rod on which the GNSS-RTK antenna is mounted. The authors experimentally determined that the bubble of the central level has the influence on the accuracy of the position, made conclusions and recommendations for reducing or eliminating the error of non-verticality of the pole

Effects and Profitability of Land Consolidation Projects: Case Study – the Republic of Serbia

An analysis of profitability and effects of land consolidation (LC) projects has been made in this paper. The measurable effects of land consolidation resulting from land consolidation goals such as: increase of average area of parcel, decrease of average number of parcels per participant as well as the change in the area of road and canal networks after the land consolidation projects were considered. Profitability was analysed from the aspect of return on investments and net present value of investment in land consolidation. Materials and methods for this study encompass a representative sample from Vojvodina, a part of the Republic of Serbia which is flatland and predominately orientated to agricultural production. The study results indicate that the effects of land consolidation are good and that land consolidation projects are highly profitable

Supplementary data for article: Đurđić, S. Z.; Sredojević, M.; Trifković, J.; Vukojević, V.; Natić, M.; Tešić, Ž. L.; Mutić, J. Elemental Composition as a Tool for the Assessment of Type, Seasonal Variability, and Geographical Origin of Wine and Its Contribution to Daily Elemental Intake. RSC Advances 2017, 7 (4), 2151–2162. https://doi.org/10.1039/c6ra25105f

Supplementary material for: [https://doi.org/10.1039/c6ra25105f]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2397

Supplementary data for the article: Stefanović, V.; Trifković, J.; Mutić, J.; Tešić, Ž. Metal Accumulation Capacity of Parasol Mushroom (Macrolepiota Procera) from Rasina Region (Serbia). Environ. Sci. Pollut. Res. 2016, 23 (13), 13178–13190. https://doi.org/10.1007/s11356-016-6486-7

Supplementary material for: [https://doi.org/10.1007/s11356-016-6486-7]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2271

Supplementary data for the article: Stojsavljević, A.; Trifković, J.; Rasić-Milutinović, Z.; Jovanović, D.; Bogdanović, G.; Mutić, J.; Manojlović, D. Determination of Toxic and Essential Trace Elements in Serum of Healthy and Hypothyroid Respondents by ICP-MS: A Chemometric Approach for Discrimination of Hypothyroidism. Journal of Trace Elements in Medicine and Biology 2018, 48, 134–140. https://doi.org/10.1016/j.jtemb.2018.03.020

Supplementary material for: [https://doi.org/10.1016/j.jtemb.2018.03.020]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2181]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3074

Elemental composition as a tool for the assessment of type, seasonal variability, and geographical origin of wine and its contribution to daily elemental intake

The elemental profiles of 63 red and white wine samples from four different regions in Serbia were investigated. Twenty-one elements were analysed (Ca, Mg, Na, K, Fe, Mn, Cu, Zn, Co, Se, Cr, V, Ni, Cd, As, Al, Sb, Pb, Ba, Rb, and Be) by inductively coupled plasma quadrupole mass spectrometry (ICP-Q-MS) and inductively coupled plasma with optical emission spectrometry (ICP-OES). A pattern recognition method was applied in order to classify and differentiate type, seasonal variability, and geographical origin of the wine. Dietary mineral intake for elements was calculated in order to assess their contribution to daily intake. The most important descriptors for discrimination among red and white wine samples were Be, Al, Rb, Mg, K, Cu, Mn, and Na, in descending order. The variables Cd, Pb, As, Sb, V, Na, K, and Zn have the highest influence on vintage-to-vintage classification of red wines. Furthermore, the model revealed the existence of three groups of descriptors for different regions of production. All obtained statistical models confirmed that data from the elemental content of wine samples could be used for accurate prediction of wine type, seasonal variability, and regional origin.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2979

Supplementary material for the article: Mesarović, J.; Trifković, J.; Tosti, T.; Fotirić Akšić, M.; Milatović, D.; Ličina, V.; Milojković-Opsenica, D. Relationship between Ripening Time and Sugar Content of Apricot (Prunus Armeniaca L.) Kernels. Acta Physiologiae Plantarum 2018, 40 (8). https://doi.org/10.1007/s11738-018-2731-7

Supplementary material for: [https://doi.org/10.1007/s11738-018-2731-7]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2193