Sinteza, struktura i svojstva 2(6)-hidroksi-6(2)-okso-N(1), 4-disuptituisanih-1,2(1,6)-dihidropiridina-3-karbonitrila i njihovih azo derivata

In this work, a simple and convenient synthesis of tautomeric (6 or 2)-hydroxy-4-methyl-(2 or 6)-oxo-1-(substituted phenyl)-(1,2 or 1,6)-dihydro- pyridine-3-carbonitriles from ethyl acetoacetate and 2-cyano-N-(substituted phenyl)-ethanamides using microwave assisted chemistry is presented. The structure of the obtained product was confirmed by the use of FTIR, NMR, UV and MS techniques. Presence of tautomeric forms, 6-hydroxy-4-methyl-2-oxo-1-(substituted phenyl)-1,2-dihydropyridine-3-carbonitriles and 2-hydroxy-4-methyl -6-oxo-1-(substituted phenyl)-1,6-dihydropyridine-3-carbonitriles, and state of equilibrium in DMSO-d6 of the obtained product was studied by 1H and 13C NMR spectroscopy, as well as B3LYP/6-311++G(d,p) and GIAO/WP04/aug-cc-pVDZ theoretical calculations. Tautomeric equilibria of title compounds were quantitatively analyzed by UV/Vis spectroscopy and theoretical approaches. Kamlet-Taft and Catalán correlation analysis were done. The LFER correlation results showed significant influence of the solvent effects on the transmission mode of substituent effects. In order to calculate optimal geometries of investigated compounds, a conformation with minimum energies were determined using semi-empirical PM6 method, as well as B3LYP (DFT) hybride method with 6-311G(d,p) basis set. The state of the tautomeric equilibria of 6(2)-hydroxy-4-methyl-2(6)-oxo-1-(substituted phenyl)-1,2(1,6)-dihydropyridine-3-carbonitriles were evaluated from UV/Vis and NMR spectral data. Quantum chemical calculations of geometries and electronic energies were performed by density functional theory (B3LYP). The experimental data were interpreted with the aid of time-dependent density functional (TD-DFT) method. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. Linear solvation energy relationships (LSER) rationalized solvent influence on tautomeric equilibrium. Linear free energy relationships (LFERs) was applied to the substituent-induced NMR chemical shifts (SCS) with σ using SSP (single substituent parameter), inductive (σI) and resonance (σR) parameters using DSP (dual substituent parameter), as well as the Yukawa–Tsuno model. Theoretical calculations and obtained correlations gave insight into the influence molecular conformation on the transmission of substituent effects, as well as on different solvent‒solute interactions on state of tautomeris equilibria.Sinteza proizvoda tautomerne smeše 2(6)-hidroksi-4-metil-6(2)-okso-1-(supstituisanih fenil)-1,2(1,6)-dihidropiridina-3-karbonitrila (serija 1), izvršena je polazeći iz etil-acetoacetata i 2-cijano-N-(supstituisanih fenil)-etanamida primenom konvencionalne i mikrotalasne metode..

Supplementary data for article: Ajaj, I.; Markovski, J.; Rančić, M.; Mijin, D.; Milčić, M.; Jovanović, M.; Marinković, A. Solvent and Structural Effects in Tautomeric 2(6)-Hydroxy-4-Methyl-6(2)-Oxo-1-(Substituted Phenyl)-1,2(1,6)-Dihydropyridine-3-Carbonitriles: UV, NMR and Quantum Chemical Study. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 2015, 150, 575–585. https://doi.org/10.1016/j.saa.2015.05.055

Supplementary material for: [https://doi.org/10.1016/j.saa.2015.05.055]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1971

Supplementary data for article: Ajaj, I. A.; Mijin, D.; Maslak, V.; Brkovic, D.; Milčić, M. K.; Todorović, N.; Marinković, A. A Simple and Convenient Synthesis of Tautomeric (6 or 2)-Hydroxy-4-Methyl-(2 or 6)-Oxo-1-(Substituted Phenyl)-(1,2 or 1,6)-Dihydropyridine-3-Carbonitriles. Monatshefte Fur Chemie 2013, 144 (5), 665–675. https://doi.org/10.1007/s00706-012-0911-5

Supplementary material for: [https://doi.org/10.1007/s00706-012-0911-5]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1587

Supplementary data for article: Ajaj, I.; Markovski, J.; Rančić, M.; Mijin, D.; Milčić, M.; Jovanović, M.; Marinković, A. Solvent and Structural Effects in Tautomeric 2(6)-Hydroxy-4-Methyl-6(2)-Oxo-1-(Substituted Phenyl)-1,2(1,6)-Dihydropyridine-3-Carbonitriles: UV, NMR and Quantum Chemical Study. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 2015, 150, 575–585. https://doi.org/10.1016/j.saa.2015.05.055

Supplementary material for: [https://doi.org/10.1016/j.saa.2015.05.055]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1971

Supplementary data for article: Ajaj, I. A.; Mijin, D.; Maslak, V.; Brkovic, D.; Milčić, M. K.; Todorović, N.; Marinković, A. A Simple and Convenient Synthesis of Tautomeric (6 or 2)-Hydroxy-4-Methyl-(2 or 6)-Oxo-1-(Substituted Phenyl)-(1,2 or 1,6)-Dihydropyridine-3-Carbonitriles. Monatshefte Fur Chemie 2013, 144 (5), 665–675. https://doi.org/10.1007/s00706-012-0911-5

Supplementary material for: [https://doi.org/10.1007/s00706-012-0911-5]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1587

Sinteza, struktura i svojstva 2(6)-hidroksi-6(2)-okso-N(1), 4-disuptituisanih-1,2(1,6)-dihidropiridina-3-karbonitrila i njihovih azo derivata edoktorska disertacija

In this work, a simple and convenient synthesis of tautomeric (6 or 2)-hydroxy-4-methyl-(2 or 6)-oxo-1-(substituted phenyl)-(1,2 or 1,6)-dihydro- pyridine-3-carbonitriles from ethyl acetoacetate and 2-cyano-N-(substituted phenyl)-ethanamides using microwave assisted chemistry is presented. The structure of the obtained product was confirmed by the use of FTIR, NMR, UV and MS techniques. Presence of tautomeric forms, 6-hydroxy-4-methyl-2-oxo-1-(substituted phenyl)-1,2-dihydropyridine-3-carbonitriles and 2-hydroxy-4-methyl -6-oxo-1-(substituted phenyl)-1,6-dihydropyridine-3-carbonitriles, and state of equilibrium in DMSO-d6 of the obtained product was studied by 1H and 13C NMR spectroscopy, as well as B3LYP/6-311++G(d,p) and GIAO/WP04/aug-cc-pVDZ theoretical calculations. Tautomeric equilibria of title compounds were quantitatively analyzed by UV/Vis spectroscopy and theoretical approaches. Kamlet-Taft and Catalán correlation analysis were done. The LFER correlation results showed significant influence of the solvent effects on the transmission mode of substituent effects. In order to calculate optimal geometries of investigated compounds, a conformation with minimum energies were determined using semi-empirical PM6 method, as well as B3LYP (DFT) hybride method with 6-311G(d,p) basis set. The state of the tautomeric equilibria of 6(2)-hydroxy-4-methyl-2(6)-oxo-1-(substituted phenyl)-1,2(1,6)-dihydropyridine-3-carbonitriles were evaluated from UV/Vis and NMR spectral data. Quantum chemical calculations of geometries and electronic energies were performed by density functional theory (B3LYP). The experimental data were interpreted with the aid of time-dependent density functional (TD-DFT) method. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. Linear solvation energy relationships (LSER) rationalized solvent influence on tautomeric equilibrium. Linear free energy relationships (LFERs) was applied to the substituent-induced NMR chemical shifts (SCS) with σ using SSP (single substituent parameter), inductive (σI) and resonance (σR) parameters using DSP (dual substituent parameter), as well as the Yukawa–Tsuno model. Theoretical calculations and obtained correlations gave insight into the influence molecular conformation on the transmission of substituent effects, as well as on different solvent‒solute interactions on state of tautomeris equilibria.Sinteza proizvoda tautomerne smeše 2(6)-hidroksi-4-metil-6(2)-okso-1-(supstituisanih fenil)-1,2(1,6)-dihidropiridina-3-karbonitrila (serija 1), izvršena je polazeći iz etil-acetoacetata i 2-cijano-N-(supstituisanih fenil)-etanamida primenom konvencionalne i mikrotalasne metode..

Sinteza, struktura i svojstva 2(6)-hidroksi-6(2)-okso-N(1), 4-disuptituisanih-1,2(1,6)-dihidropiridina-3-karbonitrila i njihovih azo derivata

In this work, a simple and convenient synthesis of tautomeric (6 or 2)-hydroxy-4-methyl-(2 or 6)-oxo-1-(substituted phenyl)-(1,2 or 1,6)-dihydro- pyridine-3-carbonitriles from ethyl acetoacetate and 2-cyano-N-(substituted phenyl)-ethanamides using microwave assisted chemistry is presented. The structure of the obtained product was confirmed by the use of FTIR, NMR, UV and MS techniques. Presence of tautomeric forms, 6-hydroxy-4-methyl-2-oxo-1-(substituted phenyl)-1,2-dihydropyridine-3-carbonitriles and 2-hydroxy-4-methyl -6-oxo-1-(substituted phenyl)-1,6-dihydropyridine-3-carbonitriles, and state of equilibrium in DMSO-d6 of the obtained product was studied by 1H and 13C NMR spectroscopy, as well as B3LYP/6-311++G(d,p) and GIAO/WP04/aug-cc-pVDZ theoretical calculations. Tautomeric equilibria of title compounds were quantitatively analyzed by UV/Vis spectroscopy and theoretical approaches. Kamlet-Taft and Catalán correlation analysis were done. The LFER correlation results showed significant influence of the solvent effects on the transmission mode of substituent effects. In order to calculate optimal geometries of investigated compounds, a conformation with minimum energies were determined using semi-empirical PM6 method, as well as B3LYP (DFT) hybride method with 6-311G(d,p) basis set. The state of the tautomeric equilibria of 6(2)-hydroxy-4-methyl-2(6)-oxo-1-(substituted phenyl)-1,2(1,6)-dihydropyridine-3-carbonitriles were evaluated from UV/Vis and NMR spectral data. Quantum chemical calculations of geometries and electronic energies were performed by density functional theory (B3LYP). The experimental data were interpreted with the aid of time-dependent density functional (TD-DFT) method. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. Linear solvation energy relationships (LSER) rationalized solvent influence on tautomeric equilibrium. Linear free energy relationships (LFERs) was applied to the substituent-induced NMR chemical shifts (SCS) with σ using SSP (single substituent parameter), inductive (σI) and resonance (σR) parameters using DSP (dual substituent parameter), as well as the Yukawa–Tsuno model. Theoretical calculations and obtained correlations gave insight into the influence molecular conformation on the transmission of substituent effects, as well as on different solvent‒solute interactions on state of tautomeris equilibria.Sinteza proizvoda tautomerne smeše 2(6)-hidroksi-4-metil-6(2)-okso-1-(supstituisanih fenil)-1,2(1,6)-dihidropiridina-3-karbonitrila (serija 1), izvršena je polazeći iz etil-acetoacetata i 2-cijano-N-(supstituisanih fenil)-etanamida primenom konvencionalne i mikrotalasne metode..

Experimental and theoretical study of substituent effect on C-13 NMR chemical shifts of 5-arylidene-2,4-thiazolidinediones

The electronic structure of 5-arylidene-2,4-thiazolidinediones has been studied by using experimental and theoretical methodology. The theoretical calculations of the investigated 5-arylidene-2,4-thiazolidinediones have been performed by the use of quantum chemical methods. The calculated C-13 NMR chemical shifts and NBO atomic charges provide an insight into the influence of such a structure on the transmission of electronic substituent effects. Linear free energy relationships (LFERs) have been further applied to their C-13 NMR chemical shifts. The correlation analyses for the substituent-induced chemical shifts (SCS) have been performed with sigma using SSP (single substituent parameter), field (sigma(F)) and resonance (sigma(R)) parameters using DSP (dual substituent parameter), as well as the Yukawa-Tsuno model. The presented correlations account satisfactorily for the polar and resonance substituent effects operative at C-beta. and C-7 carbons, while reverse substituent effect was found for C-alpha. The comparison of correlation results for the investigated molecules with those obtained for seven structurally related styrene series has indicated that specific cross-interaction of phenyl substituent and groups attached at C-alpha carbon causes increased sensitivity of SCS C-beta to the resonance effect with increasing of electron-accepting capabilities of the group present at C-beta

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population