An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA
Elektrohemijsko ispitivanje adsorpcije i interakcije vareniklina i DNK
Апстракт
The electrochemical behaviour of a novel nicotinic α4β2 subtype receptor partial agonist varenicline (VAR), which is used for smoking cessation, was investigated in Britton-Robinson buffers (pH 2.0-12.0) by cyclic, differential pulse and square wave voltammetry at a hanging mercury drop electrode (HMDE). The influence of pH, scan rate, concentration, accumulation potential and time on the peak current and potential suggested that the redox process was adsorption controlled in alkaline media. In addition, the experimental value of the surface coverage, G = 1.03×10-10 mol cm-2, was used to determine the conditions when VAR was fully adsorbed at the electrode surface. Bearing in mind the potential high toxicity of VAR due to the presence of a quinoxaline structure, its interaction with double stranded-DNA (ds-DNA) was postulated and studied when both compounds were in the adsorbed state at a modified HMDE. Using the adsorptive transfer technique, changes in potential and decreases in the ...normalized peak currents were observed. The estimated value of the ratio of surface-binding constants indicated that the reduced form of VAR interacted with ds-DNA more strongly than the oxidized form. Subtle DNA damage under conditions of direct DNA-VAR interaction at room temperature was observed. The proposed type of interaction was intercalation. This study employed a simple electroanalytical methodology and showed the potential of a DNA/ /HMDE biosensor for investigation of genotoxic effects.
Elektrohemijsko ponašanje vareniklina, novog parcijalnog agoniste α4β2 nikotinskog receptora, koji se koristi za odvikavanje od pušenja, ispitano je cikličnom, diferencijalno pulsnom i voltametrijom pravougaonih talasa u Briton-Robinsonovom puferu (pH 2,0-12,0). Na osnovu uticaja pH, brzine promene potencijala, koncentracije, potencijala i vremena akumulacije na visinu i položaj pika, zaključeno je da je proces redukcije u alkalnoj sredini kontrolisan adsorpcijom vareniklina. Korišćenjem eksperimentalno dobijene vrednosti površinske zaposednutosti, G = 1,03×10-10 mol cm-2, određeni su uslovi pod kojima je vareniklin potpuno adsorbovan na površini elektrode. Imajući u vidu moguću visoku toksičnost vareniklina, s obzirom na prisustvo hinoksalinskog prstena u strukturi, pretpostavljeno je da vareniklin interaguje sa DNK kada su oba molekula adsorbovana na modifikovanoj živinoj elektrodi. Ova interakcija je ispitana korišćenjem 'adsorptivne transfer tehnike' i primećene su promene potencij...ala i smanjenje normalizovanih struja voltametrijskih pikova. Na osnovu izračunate vrednosti odnosa konstanti vezivanja zaključeno je da se redukovani oblik vareniklina jače vezuje za DNK od oksidovanog. Pretpostavljeno je da direktna vareniklin-DNK interakcija na sobnoj temperaturi dovodi do izvesnog oštećenja DNK i da je tip interakcije - interkalacija. Ova jednostavna elektroanalitička metodologija mogla bi naći primenu u vidu potencijalnog biosenzora za ispitivanje genotoksičnih efekata.
Кључне речи:
adsorption / DNA / interaction / varenicline / electrochemistryИзвор:
Journal of the Serbian Chemical Society, 2012, 77, 10, 1409-1422Издавач:
- Srpsko hemijsko društvo, Beograd
Финансирање / пројекти:
DOI: 10.2298/JSC120420073R
ISSN: 0352-5139
WoS: 000311594100009
Scopus: 2-s2.0-84870185068
Институција/група
PharmacyTY - JOUR AU - Radulović, Valentina AU - Aleksić, Mara AU - Kapetanović, Vera PY - 2012 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1817 AB - The electrochemical behaviour of a novel nicotinic α4β2 subtype receptor partial agonist varenicline (VAR), which is used for smoking cessation, was investigated in Britton-Robinson buffers (pH 2.0-12.0) by cyclic, differential pulse and square wave voltammetry at a hanging mercury drop electrode (HMDE). The influence of pH, scan rate, concentration, accumulation potential and time on the peak current and potential suggested that the redox process was adsorption controlled in alkaline media. In addition, the experimental value of the surface coverage, G = 1.03×10-10 mol cm-2, was used to determine the conditions when VAR was fully adsorbed at the electrode surface. Bearing in mind the potential high toxicity of VAR due to the presence of a quinoxaline structure, its interaction with double stranded-DNA (ds-DNA) was postulated and studied when both compounds were in the adsorbed state at a modified HMDE. Using the adsorptive transfer technique, changes in potential and decreases in the normalized peak currents were observed. The estimated value of the ratio of surface-binding constants indicated that the reduced form of VAR interacted with ds-DNA more strongly than the oxidized form. Subtle DNA damage under conditions of direct DNA-VAR interaction at room temperature was observed. The proposed type of interaction was intercalation. This study employed a simple electroanalytical methodology and showed the potential of a DNA/ /HMDE biosensor for investigation of genotoxic effects. AB - Elektrohemijsko ponašanje vareniklina, novog parcijalnog agoniste α4β2 nikotinskog receptora, koji se koristi za odvikavanje od pušenja, ispitano je cikličnom, diferencijalno pulsnom i voltametrijom pravougaonih talasa u Briton-Robinsonovom puferu (pH 2,0-12,0). Na osnovu uticaja pH, brzine promene potencijala, koncentracije, potencijala i vremena akumulacije na visinu i položaj pika, zaključeno je da je proces redukcije u alkalnoj sredini kontrolisan adsorpcijom vareniklina. Korišćenjem eksperimentalno dobijene vrednosti površinske zaposednutosti, G = 1,03×10-10 mol cm-2, određeni su uslovi pod kojima je vareniklin potpuno adsorbovan na površini elektrode. Imajući u vidu moguću visoku toksičnost vareniklina, s obzirom na prisustvo hinoksalinskog prstena u strukturi, pretpostavljeno je da vareniklin interaguje sa DNK kada su oba molekula adsorbovana na modifikovanoj živinoj elektrodi. Ova interakcija je ispitana korišćenjem 'adsorptivne transfer tehnike' i primećene su promene potencijala i smanjenje normalizovanih struja voltametrijskih pikova. Na osnovu izračunate vrednosti odnosa konstanti vezivanja zaključeno je da se redukovani oblik vareniklina jače vezuje za DNK od oksidovanog. Pretpostavljeno je da direktna vareniklin-DNK interakcija na sobnoj temperaturi dovodi do izvesnog oštećenja DNK i da je tip interakcije - interkalacija. Ova jednostavna elektroanalitička metodologija mogla bi naći primenu u vidu potencijalnog biosenzora za ispitivanje genotoksičnih efekata. PB - Srpsko hemijsko društvo, Beograd T2 - Journal of the Serbian Chemical Society T1 - An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA T1 - Elektrohemijsko ispitivanje adsorpcije i interakcije vareniklina i DNK VL - 77 IS - 10 SP - 1409 EP - 1422 DO - 10.2298/JSC120420073R ER -
@article{ author = "Radulović, Valentina and Aleksić, Mara and Kapetanović, Vera", year = "2012", abstract = "The electrochemical behaviour of a novel nicotinic α4β2 subtype receptor partial agonist varenicline (VAR), which is used for smoking cessation, was investigated in Britton-Robinson buffers (pH 2.0-12.0) by cyclic, differential pulse and square wave voltammetry at a hanging mercury drop electrode (HMDE). The influence of pH, scan rate, concentration, accumulation potential and time on the peak current and potential suggested that the redox process was adsorption controlled in alkaline media. In addition, the experimental value of the surface coverage, G = 1.03×10-10 mol cm-2, was used to determine the conditions when VAR was fully adsorbed at the electrode surface. Bearing in mind the potential high toxicity of VAR due to the presence of a quinoxaline structure, its interaction with double stranded-DNA (ds-DNA) was postulated and studied when both compounds were in the adsorbed state at a modified HMDE. Using the adsorptive transfer technique, changes in potential and decreases in the normalized peak currents were observed. The estimated value of the ratio of surface-binding constants indicated that the reduced form of VAR interacted with ds-DNA more strongly than the oxidized form. Subtle DNA damage under conditions of direct DNA-VAR interaction at room temperature was observed. The proposed type of interaction was intercalation. This study employed a simple electroanalytical methodology and showed the potential of a DNA/ /HMDE biosensor for investigation of genotoxic effects., Elektrohemijsko ponašanje vareniklina, novog parcijalnog agoniste α4β2 nikotinskog receptora, koji se koristi za odvikavanje od pušenja, ispitano je cikličnom, diferencijalno pulsnom i voltametrijom pravougaonih talasa u Briton-Robinsonovom puferu (pH 2,0-12,0). Na osnovu uticaja pH, brzine promene potencijala, koncentracije, potencijala i vremena akumulacije na visinu i položaj pika, zaključeno je da je proces redukcije u alkalnoj sredini kontrolisan adsorpcijom vareniklina. Korišćenjem eksperimentalno dobijene vrednosti površinske zaposednutosti, G = 1,03×10-10 mol cm-2, određeni su uslovi pod kojima je vareniklin potpuno adsorbovan na površini elektrode. Imajući u vidu moguću visoku toksičnost vareniklina, s obzirom na prisustvo hinoksalinskog prstena u strukturi, pretpostavljeno je da vareniklin interaguje sa DNK kada su oba molekula adsorbovana na modifikovanoj živinoj elektrodi. Ova interakcija je ispitana korišćenjem 'adsorptivne transfer tehnike' i primećene su promene potencijala i smanjenje normalizovanih struja voltametrijskih pikova. Na osnovu izračunate vrednosti odnosa konstanti vezivanja zaključeno je da se redukovani oblik vareniklina jače vezuje za DNK od oksidovanog. Pretpostavljeno je da direktna vareniklin-DNK interakcija na sobnoj temperaturi dovodi do izvesnog oštećenja DNK i da je tip interakcije - interkalacija. Ova jednostavna elektroanalitička metodologija mogla bi naći primenu u vidu potencijalnog biosenzora za ispitivanje genotoksičnih efekata.", publisher = "Srpsko hemijsko društvo, Beograd", journal = "Journal of the Serbian Chemical Society", title = "An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA, Elektrohemijsko ispitivanje adsorpcije i interakcije vareniklina i DNK", volume = "77", number = "10", pages = "1409-1422", doi = "10.2298/JSC120420073R" }
Radulović, V., Aleksić, M.,& Kapetanović, V.. (2012). An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA. in Journal of the Serbian Chemical Society Srpsko hemijsko društvo, Beograd., 77(10), 1409-1422. https://doi.org/10.2298/JSC120420073R
Radulović V, Aleksić M, Kapetanović V. An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA. in Journal of the Serbian Chemical Society. 2012;77(10):1409-1422. doi:10.2298/JSC120420073R .
Radulović, Valentina, Aleksić, Mara, Kapetanović, Vera, "An electrochemical study of the adsorptive behaviour of varenicline and its interaction with DNA" in Journal of the Serbian Chemical Society, 77, no. 10 (2012):1409-1422, https://doi.org/10.2298/JSC120420073R . .