The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylate... more The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylated quinolone and quinoline was reported. The target compounds were synthesized employing a liquid‐assisted grinding (LAG) mechanochemical method in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) to obtain ferrocene−quinoline/quinolone hybrids (5a–5d, 6a–6d, 7a, 7b, 8a, and 8b) in higher yields and shorter reaction time compared to a conventional method, thus proving superiority of mechanochemistry versus conventional synthesis. Bis‐quinoline and bis‐quinolone ferrocene derivatives were evaluated for their antiproliferative effects on five selected tumor and two non‐tumor cell lines. Bis‐6‐methylquinolone–ferrocene conjugate 8b showed the best antiproliferative effect on T‐cell lymphoma (HuT78) cells (IC50 = 14.8 μM) and no cytotoxicity on both non‐tumor MDCK1 and BJ cells. Results obtained after mitochondrial membrane potential (∆Ψm) measurement using flow cytometry showed that compo...
A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism u... more A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The SN2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (N7/N9-ferrocenoyl isomers) is governed by the steric property of the substituent at the N6-position. Steric effects were evaluated by using Charton (empirical) and Sterimol (computational) parameters. The bulky substituents may shield the proximal N7 region of space, which prevents the approach of an electrophile towards the N7 atom. As a consequence, the formation of N7-isomer is a kinetically less feasible process, i.e., the corresponding transition state structure increases in relative energy (compared to the formation of the N9-isomer). In cases where the steric hindrance is negligible, the electronic effect of the N6-substituent is prevailing. That was supported by calculations of Fukui functions and molecular orbital coe...
Nucleobases substituted by ferrocenyl moiety present interesting organometallic conjugates due to... more Nucleobases substituted by ferrocenyl moiety present interesting organometallic conjugates due to their structures which incorporate both biologically and electrochemically active components. Synthetic procedures for preparation of N1- and N3-ferrocenyl substituted pyrimidine bases (thymine, cytosine) and N9-ferrocenyl substituted purine base (adenine) have been developed. The position of substitution in products has been confirmed by spectroscopy methods (NOESY-NMR, IR). Quantum chemical calculations (DFT level of theory) have been employed to rationalize the preferential reaction of ferrocenecarbonyl chloride with N1-nitrogen atom in pyrimidine nucleobases. The calculated energy of activation for the reaction at N3-position is ca. 30 kJ/mol higher than the barrier for the corresponding reaction at N1-position. In addition, N1-ferrocenyl substituted nucleobases have been calculated more stable than their N3-substituted counterparts. Substitution of pyrimidine and purine bases with ...
Fruits and vegetables are rich in polyphenols, which are the major source of antioxidants in diet... more Fruits and vegetables are rich in polyphenols, which are the major source of antioxidants in diet, with a number of positive effects on human health. The balance between the production of free radicals and antioxidant intake is very important because of the stress that is present in every organism. In this study was used a standard method like determination of total phenols with Folin-Ciocalteu reagent and some methods that are rarely used in the analysis of samples which are rich in polyphenols, such as near-infrared spectroscopy and Briggs-Rauscher reaction. Wild berries offer a range of vitamins, minerals and phytochemicals, and the most of them have antioxidant properties. The aim of this work was to examine the berries (strawberries, blackberries, raspberries, blueberries and red currants) by determining the share of total phenols (TP), the antioxidant activity using the Briggs-Rauscher’s method (BRAI), and determination of the colorimetric and near infrared spectroscopy (NIRs)...
The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylate... more The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylated quinolone and quinoline was reported. The target compounds were synthesized employing a liquid‐assisted grinding (LAG) mechanochemical method in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) to obtain ferrocene−quinoline/quinolone hybrids (5a–5d, 6a–6d, 7a, 7b, 8a, and 8b) in higher yields and shorter reaction time compared to a conventional method, thus proving superiority of mechanochemistry versus conventional synthesis. Bis‐quinoline and bis‐quinolone ferrocene derivatives were evaluated for their antiproliferative effects on five selected tumor and two non‐tumor cell lines. Bis‐6‐methylquinolone–ferrocene conjugate 8b showed the best antiproliferative effect on T‐cell lymphoma (HuT78) cells (IC50 = 14.8 μM) and no cytotoxicity on both non‐tumor MDCK1 and BJ cells. Results obtained after mitochondrial membrane potential (∆Ψm) measurement using flow cytometry showed that compo...
A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism u... more A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The SN2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (N7/N9-ferrocenoyl isomers) is governed by the steric property of the substituent at the N6-position. Steric effects were evaluated by using Charton (empirical) and Sterimol (computational) parameters. The bulky substituents may shield the proximal N7 region of space, which prevents the approach of an electrophile towards the N7 atom. As a consequence, the formation of N7-isomer is a kinetically less feasible process, i.e., the corresponding transition state structure increases in relative energy (compared to the formation of the N9-isomer). In cases where the steric hindrance is negligible, the electronic effect of the N6-substituent is prevailing. That was supported by calculations of Fukui functions and molecular orbital coe...
Nucleobases substituted by ferrocenyl moiety present interesting organometallic conjugates due to... more Nucleobases substituted by ferrocenyl moiety present interesting organometallic conjugates due to their structures which incorporate both biologically and electrochemically active components. Synthetic procedures for preparation of N1- and N3-ferrocenyl substituted pyrimidine bases (thymine, cytosine) and N9-ferrocenyl substituted purine base (adenine) have been developed. The position of substitution in products has been confirmed by spectroscopy methods (NOESY-NMR, IR). Quantum chemical calculations (DFT level of theory) have been employed to rationalize the preferential reaction of ferrocenecarbonyl chloride with N1-nitrogen atom in pyrimidine nucleobases. The calculated energy of activation for the reaction at N3-position is ca. 30 kJ/mol higher than the barrier for the corresponding reaction at N1-position. In addition, N1-ferrocenyl substituted nucleobases have been calculated more stable than their N3-substituted counterparts. Substitution of pyrimidine and purine bases with ...
Fruits and vegetables are rich in polyphenols, which are the major source of antioxidants in diet... more Fruits and vegetables are rich in polyphenols, which are the major source of antioxidants in diet, with a number of positive effects on human health. The balance between the production of free radicals and antioxidant intake is very important because of the stress that is present in every organism. In this study was used a standard method like determination of total phenols with Folin-Ciocalteu reagent and some methods that are rarely used in the analysis of samples which are rich in polyphenols, such as near-infrared spectroscopy and Briggs-Rauscher reaction. Wild berries offer a range of vitamins, minerals and phytochemicals, and the most of them have antioxidant properties. The aim of this work was to examine the berries (strawberries, blackberries, raspberries, blueberries and red currants) by determining the share of total phenols (TP), the antioxidant activity using the Briggs-Rauscher’s method (BRAI), and determination of the colorimetric and near infrared spectroscopy (NIRs)...
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Papers by Senka Djaković