Papers by Adelina Voutchkova
Basic toxicological information is lacking for the majority of industrial chemicals. In addition ... more Basic toxicological information is lacking for the majority of industrial chemicals. In addition to increasing empirical toxicity data through additional testing, prospective computational approaches to drug development aim to serve as a rational basis for the design of chemicals with reduced toxicity. Recent work has resulted in the derivation of a " rule of 2, " wherein chemicals with an octanol–water partition coefficient (log P) less than 2 and a difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital (~E) greater than 9 (log P < 2 and ~E > 9 eV) are predicted to be 4 to 5 times less likely to elicit acute or chronic toxicity to model aquatic organisms. The present study examines potential reduction of aquatic toxicity hazards from industrial chemicals if these 2 molecular design guidelines were employed. Probabilistic hazard assessment approaches were used to model the likelihood of encountering industrial chemicals exceeding toxicological categories of concern both with and without the rule of 2. Modeling predicted that utilization of these molecular design guidelines for log P and ~E would appreciably decrease the number of chemicals that would be designated to be of " high " and " very high " concern for acute and chronic toxicity to standard model aquatic organisms and end points as defined by the US Environmental Protection Agency. For example, 14.5% of chemicals were categorized as having high and very high acute toxicity to the fathead minnow model, whereas only 3.3% of chemicals conforming to the design guidelines were predicted to be in these categories. Considerations of specific chemical classes (e.g., aldehydes), chemical attributes (e.g., ionization), and adverse outcome pathways in representative species (e.g., receptor-mediated responses) could be used to derive future property guidelines for broader classes of contaminants. Environ Toxicol Chem 2014;33:1894–1902. # 2014 SETAC
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Green Chemistry, 2020
Thermally-robust and water-soluble Ir(i) and Ir(iii) N-heterocyclic carbene complexes with sulfon... more Thermally-robust and water-soluble Ir(i) and Ir(iii) N-heterocyclic carbene complexes with sulfonate functionalized wingtips are prolific catalysts for carbonate transfer hydrogenation from glycerol without additives in aqueous media.
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Green Chemistry, 2016
In silico toxicity models are critical in addressing experimental aquatic toxicity data gaps and ... more In silico toxicity models are critical in addressing experimental aquatic toxicity data gaps and prioritizing chemicals for further assessment.
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Green Chemistry, 2016
A predictive method is reported for estimating skin permeation of organic chemicals exclusively f... more A predictive method is reported for estimating skin permeation of organic chemicals exclusively from NMR spectroscopic data and molecular weight, which does not require knowledge of chemical structure.
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Chemical Research in Toxicology, 2016
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RSC Advances, 2015
We report a new covalent surface immobilization of silane-modified imidazolium ionic liquids on h... more We report a new covalent surface immobilization of silane-modified imidazolium ionic liquids on hydrotalcite-like materials (HTs) and provide detailed characterization of the resulting surface chemistry using PXRD, CP-MAS, TGA and FT-IR.
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Green Chemistry, 2015
Intrinsic catalytic activity of a series of hydrotalcite-like materials towards acceptorless alco... more Intrinsic catalytic activity of a series of hydrotalcite-like materials towards acceptorless alcohol dehydrogenation and one-pot imination.
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Handbook of Green Chemistry, 2012
ABSTRACT The sections in this article arePossible Approaches to Systematic Design Guidelines for ... more ABSTRACT The sections in this article arePossible Approaches to Systematic Design Guidelines for Reduced ToxicityAnalogy with Medicinal ChemistryDo Chemicals with Similar Toxicity Profiles Have Similar Physical/Chemical Properties?Proposed Design Guidelines for Reduced Human ToxicityConsiderations for Reducing Human AbsorptionExample: Reducing Carcinogenicity by Decreasing Oral BioavailabilityUsing Property Guidelines to Design for Reducing Acute Aquatic ToxicityPredicting the Physicochemical Properties and Attributes Needed for Developing Design RulesSolvent-Related PropertiesHydrophobicitySolubilitypKaElectronic PropertiesOrbital EnergiesMolecular Dipole Moment and PolarizabilityMolecular Surface AreaConclusion Keywords:design rules;property guidelines;reduced toxicity;safer chemicals;green chemistry
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Tetrahedron, 2010
The relationship of in-silico predicted physical/chemical properties and human toxicity is analyz... more The relationship of in-silico predicted physical/chemical properties and human toxicity is analyzed for a statistically significant sample size of chemical compounds. Results for compounds with known toxicity endpoints, as designated by EPA's Toxic Release Inventory (TRI), are compared to a series of commercial chemicals that are not regulated under TRI. Physical properties for all compounds are predicted using Schrodinger's QikProp,
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Proceedings of the National Academy of Sciences, 2014
Significance Two of the rigorous disciplines that have emerged over the last 20 y to empower sust... more Significance Two of the rigorous disciplines that have emerged over the last 20 y to empower sustainability science are industrial ecology and green chemistry. Robust assessment tools of industrial ecology identify the greatest opportunities to mitigate human health and environmental impacts resulting from human activity. Green chemistry designs and develops chemicals, materials, and processes that, throughout the life cycle, minimize hazard and maximize efficiency. This process often entails synthesizing new molecules while maintaining function and minimizing adverse outcomes, particularly toxicity. There is an urgent need to develop accurate and economical screening tools that predict potential toxicity and inform the design of safer alternatives. A computational approach is presented for the rational design of molecules for reduced acute aquatic toxicity.
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Organic Letters, 2012
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Molecular Informatics, 2014
The ability to estimate chemical and physical properties from experimental spectra is highly desi... more The ability to estimate chemical and physical properties from experimental spectra is highly desirable, as it eliminates the need for a priori knowledge of exact chemical structure and allows the property estimation of mixtures. Here we report the proof of principle that a predictive method for octanol-water partition coefficient (logP) based on (1) H-NMR spectra in d(3) -chloroform is feasible and can yield accuracy comparable to in silico logP models. The Spectrometric Data-Activity Relationship (QSDAR) reported predicts logP of neutral organic chemicals using descriptors derived only from (1) H-NMR chemical shifts, integrations and peak widths. Proton NMR spectra of 140 compounds with diverse structures were used to construct a Multiple Linear Regression (MLR) and a Partial Least Squares (PLS) model that predicts logP. The optimized models were internally validated by K-fold cross validation and leave-one-out validation, and externally with a test set of 28 chemicals. The squared regression coefficients of prediction for the MLR and PLS regression models were 0.970 and 0.971 respectively, showing that the method allows accurate prediction of logP values exclusively from predicted (1) H NMR spectra.
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Journal of the American Chemical Society, 2005
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Journal of the American Chemical Society, 2005
Many transition-metal complexes mediate DNA oxidation in the presence of oxidizing radiation, pho... more Many transition-metal complexes mediate DNA oxidation in the presence of oxidizing radiation, photosensitizers, or oxidants. The DNA oxidation products depend on the nature of the metal complex and the structure of the DNA. Earlier we reported trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum (trans-Pt(d,l)(1,2-(NH(2))(2)C(6)H(10))Cl(4), [Pt(IV)Cl(4)(dach)]; dach = diaminocyclohexane) oxidizes 2'-deoxyguanosine 5'-monophosphate (5'-dGMP) to 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-5'-dGMP) stoichiometrically. In this paper we report that [Pt(IV)Cl(4)(dach)] also oxidizes 2'-deoxyguanosine 3'-monophosphate (3'-dGMP) stoichiometrically. The final oxidation product is not 8-oxo-3'-dGMP, but cyclic (5'-O-C8)-3'-dGMP. The reaction was studied by high-performance liquid chromatography, (1)H and (31)P nuclear magnetic resonance, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The proposed mechanism involves Pt(IV) binding to N7 of 3'-dGMP followed by nucleophilic attack of a 5'-hydroxyl oxygen to C8 of G and an inner-sphere, 2e(-) transfer to produce cyclic (5'-O-C8)-3'-dGMP and [Pt(II)Cl(2)(dach)]. The same mechanism applies to 5'-d[GTTTT]-3', where the 5'-dG is oxidized to cyclic (5'-O-C8)-dG. The Pt(IV) complex binds to N7 of guanine in cGMP, 9-Mxan, 5'-d[TTGTT]-3', and 5'-d[TTTTG]-3', but no subsequent transfer of electrons occurs in these. The results indicate that a good nucleophilic group at the 5' position is required for the redox reaction between guanosine and the Pt(IV) complex.
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Journal of the American Chemical Society, 2007
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Journal of Organometallic Chemistry, 2008
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Journal of Molecular Catalysis A: Chemical, 2009
ABSTRACT A recyclable catalyst, Ir/C, gives C–H benzylic functionalization of simple arenes to af... more ABSTRACT A recyclable catalyst, Ir/C, gives C–H benzylic functionalization of simple arenes to afford aldehydes, esters, and imines. In the case of esters, an additive, Ag2CO3, acts as base and oxidant, while for imine formation no additive is necessary. In this latter case a double C–H activation is proposed, accompanied by loss of H2.
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Green Chemistry, 2012
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Green Chemistry, 2011
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Green Chemistry, 2007
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Papers by Adelina Voutchkova