The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Therefore, herein acid dissociation constant; pKa, lipophilicity; logP, polar surface area, hydrogen bond donor and acceptor counts of structurally different oximes (two tertiary oximes and thirteen pyridinium aldoxime derivatives) have been evaluated. The experimentally obtained data for pKa has been comparatively analyzed by using non-linear regression. Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. The pKa values of all the examined oximes were within the range of 7.50-9.53. pKa values of uncharged and mono-pyridinium oximes were in good correlation with their reactivation potency. The high negative logP values of pyridinium oxime reactivators indicate their high hydrophilic character; hence oximes with improved lipophilicity should be designed for the development of novel and more potent antidotes. Propane and butane linked oximes were superior reactivators than xylene linked bis-oxime reactivators. It is concluded from the present study that pKa value is not only ruled by the position of oximino functionality in the pyridinium ring, but also by the position of linker. Although, pyridinium oximes are proved to be better reactivators but their lipophilicity has to be improved.

Department of Chemistry and Biochemistry Faculty of Medicine University of Zargreb Šalata 3 10000 Zagreb Croatia

Process Technology Development Division Defence Research and Development Establishment Jhansi Road Gwalior 474002 India

School of Studies in Chemistry Pt Ravishankar Shukla University Raipur 492010 India

University Hospital Biomedical Research Center Sokolska 581 50005 Hradec Kralove Czech Republic

University of Hradec Kralove Faculty of Science Department of Chemistry Rokitanskeho 62 Hradec Kralove Czech Republic

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$a Gupta, Bhanushree $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India.

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$a Assessment of antidotal efficacy of cholinesterase reactivators against paraoxon: In vitro reactivation kinetics and physicochemical properties / $c B. Gupta, N. Singh, R. Sharma, B. Foretić, K. Musilek, K. Kuca, J. Acharya, ML. Satnami, KK. Ghosh,

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$a The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Therefore, herein acid dissociation constant; pKa, lipophilicity; logP, polar surface area, hydrogen bond donor and acceptor counts of structurally different oximes (two tertiary oximes and thirteen pyridinium aldoxime derivatives) have been evaluated. The experimentally obtained data for pKa has been comparatively analyzed by using non-linear regression. Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. The pKa values of all the examined oximes were within the range of 7.50-9.53. pKa values of uncharged and mono-pyridinium oximes were in good correlation with their reactivation potency. The high negative logP values of pyridinium oxime reactivators indicate their high hydrophilic character; hence oximes with improved lipophilicity should be designed for the development of novel and more potent antidotes. Propane and butane linked oximes were superior reactivators than xylene linked bis-oxime reactivators. It is concluded from the present study that pKa value is not only ruled by the position of oximino functionality in the pyridinium ring, but also by the position of linker. Although, pyridinium oximes are proved to be better reactivators but their lipophilicity has to be improved.

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$a Singh, Namrata $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India.

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$a Sharma, Rahul $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India.

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$a Foretić, Blaženka $u Department of Chemistry and Biochemistry, Faculty of Medicine, University of Zargreb, Šalata 3, 10000 Zagreb, Croatia.

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$a Musilek, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove, Czech Republic.

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$a Kuca, Kamil $u University Hospital, Biomedical Research Center, Sokolska 581, 50005 Hradec Kralove, Czech Republic.

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$a Satnami, M L $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India.

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$a Ghosh, Kallol K $u School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India. Electronic address: kallolkghosh@yahoo.com.

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