The logarithms of retention factors normalized to a hypothetical pure water eluent(log k w) were determined on a reversed phase high performance liquid chromatography(RP HPLC) column (Li Chrosorb RP 18 column...The logarithms of retention factors normalized to a hypothetical pure water eluent(log k w) were determined on a reversed phase high performance liquid chromatography(RP HPLC) column (Li Chrosorb RP 18 column) for 20 new α\|branched phenylsulfonyl acetates. The atomic charge method was applied to develop quantitative structure retention relationships(QSRRs). Among the available geometric and electronic descriptors, surface area (S), ovality (O), and the charge of carboxyl group(Q OC ) are significant. In the model, the contribution of surface area (S) is the greatest. The molecular mechanism of retention was demonstrated through the model. With the correlation coefficient ( r 2 adj , adjusted for degrees of freedom) of 0.964, the standard error of 0.164 and the F value of 170.39, the model has good predictive capacity.展开更多
A 3-Dimension-Quantitative Structure-Activity Relationship</span></span><span><span><span style="font-family:""> (</span></span></span><span><spa...A 3-Dimension-Quantitative Structure-Activity Relationship</span></span><span><span><span style="font-family:""> (</span></span></span><span><span><span style="font-family:"">3D-QSAR</span></span></span><span><span><sup><span style="font-family:"">1</span></sup></span></span><span><span><span style="font-family:"">) </span></span></span><span><span><span style="font-family:"">approach is applied for the prediction of accurate chemical</span></span></span><span><span><span style="font-family:""> products made from biological activity and toxicity. Quantum chemical technique allows the construction of the molecular descriptors. The molecular quantum descriptors are classified into five principal component factors. Various linear <span>regression equations are obtained using the statistical technique. In this</span> study, the researchers propose the three best regression equations based on quantum molecular descriptors discussed earlier in this study. The observed EC50 vs calculated EC50 is plotted using the best fitting with the quantum descriptors.展开更多
A detailed quantum mechanical analysis of electronic disposition of five aminopyrimidoisoquinolinequinones (APIQs) was performed after extraction of this subset of compounds from a larger data set of APIQs via a repor...A detailed quantum mechanical analysis of electronic disposition of five aminopyrimidoisoquinolinequinones (APIQs) was performed after extraction of this subset of compounds from a larger data set of APIQs via a reported clustering methodology (Elfaki, et al. 2020). Both semi empirical PM3 method and DFT quantum mechanical methods were used to calculate global and local quantum mechanical descriptors (QMDs) to define the electronic environment of these molecules in attempt to rationalize their observed anti-cancer response variability. The biological response is the anticancer activity against human gastric adenocarcenoma (AGS) cell line. The correlation matrix between the calculated global electronic descriptors and biological activity demonstrated that the global dipole moment gives the highest correlation. The local electronic environment was analysed by The Mullikan charges (MC) and Fukui functions for N-5, C-6, C-8 in addition to the N atom of phenylamino side group at C-8. MCs furnished no useful information as each of these atoms had almost identical MC values for all the five compounds with exception of C-6 which gave varied values. Regressing MCs of C-6 against the response traces 60% of the latter variability. As C-6 is an extra annular methyl carbon adjacent to N-5 in isoquinoline residue of APIQ, we reasoned that the chemical reactivities of 4 out of the 5 APIQs might be due to a Chichibabin-type tautomerism implying a possible alkylation aspect in their mechanism of action. The corresponding Fukui functions (f<sup>-</sup>, f<sup>+</sup> and f<sup>0</sup>) showed a considerable consistency with the patterns of chemical reactivity exhibited by this small set of APIQs.展开更多
The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven huma...The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC<sub>50</sub>s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC<sub>50</sub>s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (E<sub>elec</sub>), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.展开更多
The photolysis of 16 polychlorinated biphenyls （PCBs） （including mono- through deca-chlorinated） in n-hexane was investigated under ultraviolet irradiation using a 500-W high-pressure mercury lamp. Photolysis of P...The photolysis of 16 polychlorinated biphenyls （PCBs） （including mono- through deca-chlorinated） in n-hexane was investigated under ultraviolet irradiation using a 500-W high-pressure mercury lamp. Photolysis of PCBs follows pseudo-first-order reaction kinetics, with photolysis rate constants ranging between 0.0011 s^-1 for PCB-52 and 0.0574 s^-1 for PCB-118. The degradation rates of PCBs by high-pressure mercury lamp irradiation were remarkably independent with respect to the degree of chlorination. Furthermore, partial least squares （PLS） models were developed to provide insight into which aspect of the molecular structure influenced PCB photolysis rate constants. It was found that the photolysis rates of PCBs increased with an increase in the net charge on the carbon atom （qc）, （ELUMO-EHOMO）^2, and the Y-axis dipole moment （μy） values, or the decrease in the energy of the second highest occupied molecular orbital （EHOMO-1）, energy of the lowest unoccupied molecular orbital （ELUMO）, ELUMO ＋ EHOMO, ELUMO - EHOMO, most positive atomic charge （q^＋）, and the twist angle of the chlorine atom （TA） values.展开更多
Quantitative structure-property relationship(QSPR)models were developed for prediction of photolysis half-life(t_(1/2))of polychlorinated biphenyls(PCBs)in water under ultraviolet(UV)radiation.Quantum chemical descrip...Quantitative structure-property relationship(QSPR)models were developed for prediction of photolysis half-life(t_(1/2))of polychlorinated biphenyls(PCBs)in water under ultraviolet(UV)radiation.Quantum chemical descriptors computed by the PM3 Hamiltonian software were used as independent variables.The cross-validated Q^(2)_(cum)value for the optimal QSPR model is 0.966,indicating good prediction capability for lg t_(1/2)values of PCBs in water.The QSPR results show that the largest negative atomic charge on a carbon atom(Q-C)and the standard heat of formation(ΔH_(f))have a dominant effect on t_(1/2)values of PCBs.Higher Q_(C)^(-)values or lowerΔHf values of the PCBs leads to higher lg t_(1/2)values.In addition,the lg t_(1/2)values of PCBs increase with the increase in the energy of the highest occupied molecular orbital values.Increasing the largest positive atomic charge on a chlorine atom and the most positive net atomic charge on a hydrogen atom in PCBs leads to the decrease of lg t_(1/2)values.展开更多
Based on quantum chemical calculations, TLSER model(theoretical linear solvation energy relationships) and atomic charge approach were applied to model the partition properties(water solubility and octanol/water parti...Based on quantum chemical calculations, TLSER model(theoretical linear solvation energy relationships) and atomic charge approach were applied to model the partition properties(water solubility and octanol/water partition coefficient) of 96 aromatic sulfur-containing carboxylates, including phenylthio, phenylsulfinyl and phenylsulfonyl carboxylates. In comparison with TLSER models, the atomic charge models are more accurate and reliable to predict the partition properties of the kind of compounds. For the atomic charge models, the molecular descriptors are molecular surface area(S), molecular shape(O), weight(M W), net charges on carboxyl group(Q OC), net charges of nitrogen atoms(Q N), and the most negative atomic charge(q -) of the solute molecule. For water solubility(log S W) and octanol/water partition coefficient(log K OW), the correction coefficients r 2 adj(adjusted for degrees of freedom) are 0.936 and 0.938, and the standard deviations are 0.364 and 0.223, respectively.展开更多
Using density functional theory, noncovalent interactions and two mechanisms of covalent functionalization of drug carmustine with functionalized carbon nanotube（CNT） have been investigated. Quantum molecular descri...Using density functional theory, noncovalent interactions and two mechanisms of covalent functionalization of drug carmustine with functionalized carbon nanotube（CNT） have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug carmustine with functionalized CNT is thermodynamically suitable. NTCOOH and NTCOCl can bond to the NH group of carmustine through OH（COOH mechanism） and Cl（COCl mechanism） groups, respectively. The activation energies, activation enthalpies and activation Gibbs free energies of two pathways were calculated and compared with each other. The activation parameters related to COOH mechanism are higher than those related to COCl mechanism, and therefore COCl mechanism is suitable for covalent functionalization. COOH functionalized CNT（NTCOOH） has more binding energy than COCl functionalized CNT（NTCOCl） and can act as a favorable system for carmustine drug delivery within biological and chemical systems（noncovalent）. These results could be generalized to other similar drugs.展开更多
The regression model for octanol/water partition coefficients ( K ow ), is founded with only two molecular descriptors available through quantum chemical calculations: solvation free energy (Δ G S ), and so...The regression model for octanol/water partition coefficients ( K ow ), is founded with only two molecular descriptors available through quantum chemical calculations: solvation free energy (Δ G S ), and solvent accessible surface area (SASA). For the properties of 47 organic compounds from 17 types, the model gives a correction coefficient (adjusted for degrees of freedom) of 0 959 and a standard error of 0 277 log unit. It is a suitable way to predict the partition properties that are related to solute solvent interactions in the water phase.展开更多
The distribution of organic compounds in stored lipids affects their migration,transformation,bioaccumulation,and toxicity in organisms.The storage lipid/water distribution coefficient(log K_(lip/w))of organic chemica...The distribution of organic compounds in stored lipids affects their migration,transformation,bioaccumulation,and toxicity in organisms.The storage lipid/water distribution coefficient(log K_(lip/w))of organic chemicals,which quantitatively determines such distribution,has become a key parameter to assist their ecological security and health risk.Due to the impossibility to measure K_(lip/w)values for a huge amount of chemicals,it is necessary to develop predictive approaches.In this work,a quantitative structure-property relationship(QSPR)model for estimating log K_(lip/w)values of small organic compounds was constructed based on 305 experimental log K_(lip/w)values.Quantum chemical descriptors and n-octanol/water partitioning coefficient were employed to characterize the intermolecular interactions that dominate log K_(lip/w)values.The hydrophobic and electrostatic interactions and molecular size have been found to play important roles in governing the distribution of chemicals between lipids and aqueous phases.The regression(R2=0.959)and validation(Q2=0.960)results indicate good fitting performance and robustness of the developed model.A comparison with the predictive performance of other commercial software further proves the higher accuracy and stronger predictive ability of the developed K_(lip/w)predictive model.Thus,it can be used to predict the K_(lip/w)values of cycloalkanes,long-chain alkanes,halides(with fluorine,chlorine,and bromine as substituents),esters(without phosphate groups),alcohols(without methoxy groups),and aromatic compounds.展开更多
In this work a multi-objective quantitative structure-property relationship (QSPR) analysis approach was reported based on the study on three partition properties of 50 aromatic sulfur-containing carboxylates. Here mu...In this work a multi-objective quantitative structure-property relationship (QSPR) analysis approach was reported based on the study on three partition properties of 50 aromatic sulfur-containing carboxylates. Here multi-objectives (properties) were taken as a vector for QSPR modeling. The quantitative correlations for partition properties were developed using a genetic algorithm-based variable-selection approach with quantum chemical descriptors derived from AM1-based calculations. With the QSPR models, the aqueous solubility, octanol/water partition coefficients and reversed-phase HPLC capacity factors of sulfur-containing compounds were estimated and predicted. Using GA-based multivariate linear regression with cross-validation procedure, a set of the most promising descriptors was selected from a pool of 28 quantum chemical semi-empirical descriptors, including steric and electronic types, to integrally build QSPR models. The selected molecular descriptors included the net charges on carboxyl group (Q OC), the 2nd power of net charges on nitrogen atoms (Q 2 N), the net atomic charge on the sulfur atoms (Q S), the van der Waals volume of molecule (V), the most positive net atomic charge on hydrogen atoms (Q H) and the measure of polarity and polarizability (π), which were main factors affecting the distribution processes of the compounds under study. The statistically best QSPR models of six descriptors were simultaneously obtained by GA-based linear regression analysis. With the selected descriptors and the QSPR equations, mechanisms of partition action of the Sulfur-containing carboxylates were able to be investigated and interpreted.展开更多
基金TheNationalNaturalScienceFoundationofChina (No .2 9837180 )
文摘The logarithms of retention factors normalized to a hypothetical pure water eluent(log k w) were determined on a reversed phase high performance liquid chromatography(RP HPLC) column (Li Chrosorb RP 18 column) for 20 new α\|branched phenylsulfonyl acetates. The atomic charge method was applied to develop quantitative structure retention relationships(QSRRs). Among the available geometric and electronic descriptors, surface area (S), ovality (O), and the charge of carboxyl group(Q OC ) are significant. In the model, the contribution of surface area (S) is the greatest. The molecular mechanism of retention was demonstrated through the model. With the correlation coefficient ( r 2 adj , adjusted for degrees of freedom) of 0.964, the standard error of 0.164 and the F value of 170.39, the model has good predictive capacity.
文摘A 3-Dimension-Quantitative Structure-Activity Relationship</span></span><span><span><span style="font-family:""> (</span></span></span><span><span><span style="font-family:"">3D-QSAR</span></span></span><span><span><sup><span style="font-family:"">1</span></sup></span></span><span><span><span style="font-family:"">) </span></span></span><span><span><span style="font-family:"">approach is applied for the prediction of accurate chemical</span></span></span><span><span><span style="font-family:""> products made from biological activity and toxicity. Quantum chemical technique allows the construction of the molecular descriptors. The molecular quantum descriptors are classified into five principal component factors. Various linear <span>regression equations are obtained using the statistical technique. In this</span> study, the researchers propose the three best regression equations based on quantum molecular descriptors discussed earlier in this study. The observed EC50 vs calculated EC50 is plotted using the best fitting with the quantum descriptors.
文摘A detailed quantum mechanical analysis of electronic disposition of five aminopyrimidoisoquinolinequinones (APIQs) was performed after extraction of this subset of compounds from a larger data set of APIQs via a reported clustering methodology (Elfaki, et al. 2020). Both semi empirical PM3 method and DFT quantum mechanical methods were used to calculate global and local quantum mechanical descriptors (QMDs) to define the electronic environment of these molecules in attempt to rationalize their observed anti-cancer response variability. The biological response is the anticancer activity against human gastric adenocarcenoma (AGS) cell line. The correlation matrix between the calculated global electronic descriptors and biological activity demonstrated that the global dipole moment gives the highest correlation. The local electronic environment was analysed by The Mullikan charges (MC) and Fukui functions for N-5, C-6, C-8 in addition to the N atom of phenylamino side group at C-8. MCs furnished no useful information as each of these atoms had almost identical MC values for all the five compounds with exception of C-6 which gave varied values. Regressing MCs of C-6 against the response traces 60% of the latter variability. As C-6 is an extra annular methyl carbon adjacent to N-5 in isoquinoline residue of APIQ, we reasoned that the chemical reactivities of 4 out of the 5 APIQs might be due to a Chichibabin-type tautomerism implying a possible alkylation aspect in their mechanism of action. The corresponding Fukui functions (f<sup>-</sup>, f<sup>+</sup> and f<sup>0</sup>) showed a considerable consistency with the patterns of chemical reactivity exhibited by this small set of APIQs.
文摘The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC<sub>50</sub>s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC<sub>50</sub>s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (E<sub>elec</sub>), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.
基金This work was supported by the National Natural Science Foundation of China(No.20507010)the Excellent Young Scientist Fund of China(No.50625823).
文摘The photolysis of 16 polychlorinated biphenyls （PCBs） （including mono- through deca-chlorinated） in n-hexane was investigated under ultraviolet irradiation using a 500-W high-pressure mercury lamp. Photolysis of PCBs follows pseudo-first-order reaction kinetics, with photolysis rate constants ranging between 0.0011 s^-1 for PCB-52 and 0.0574 s^-1 for PCB-118. The degradation rates of PCBs by high-pressure mercury lamp irradiation were remarkably independent with respect to the degree of chlorination. Furthermore, partial least squares （PLS） models were developed to provide insight into which aspect of the molecular structure influenced PCB photolysis rate constants. It was found that the photolysis rates of PCBs increased with an increase in the net charge on the carbon atom （qc）, （ELUMO-EHOMO）^2, and the Y-axis dipole moment （μy） values, or the decrease in the energy of the second highest occupied molecular orbital （EHOMO-1）, energy of the lowest unoccupied molecular orbital （ELUMO）, ELUMO ＋ EHOMO, ELUMO - EHOMO, most positive atomic charge （q^＋）, and the twist angle of the chlorine atom （TA） values.
基金The research was supported by the Open Foundation of the State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering(No.2009490511)the special fund of State Key Joint Laboratory of Environment Simulation and Pollution Control(No.10Y08ESPCN)the National High Technology Research and Development Program of China(No.2009AA05Z306).
文摘Quantitative structure-property relationship(QSPR)models were developed for prediction of photolysis half-life(t_(1/2))of polychlorinated biphenyls(PCBs)in water under ultraviolet(UV)radiation.Quantum chemical descriptors computed by the PM3 Hamiltonian software were used as independent variables.The cross-validated Q^(2)_(cum)value for the optimal QSPR model is 0.966,indicating good prediction capability for lg t_(1/2)values of PCBs in water.The QSPR results show that the largest negative atomic charge on a carbon atom(Q-C)and the standard heat of formation(ΔH_(f))have a dominant effect on t_(1/2)values of PCBs.Higher Q_(C)^(-)values or lowerΔHf values of the PCBs leads to higher lg t_(1/2)values.In addition,the lg t_(1/2)values of PCBs increase with the increase in the energy of the highest occupied molecular orbital values.Increasing the largest positive atomic charge on a chlorine atom and the most positive net atomic charge on a hydrogen atom in PCBs leads to the decrease of lg t_(1/2)values.
文摘Based on quantum chemical calculations, TLSER model(theoretical linear solvation energy relationships) and atomic charge approach were applied to model the partition properties(water solubility and octanol/water partition coefficient) of 96 aromatic sulfur-containing carboxylates, including phenylthio, phenylsulfinyl and phenylsulfonyl carboxylates. In comparison with TLSER models, the atomic charge models are more accurate and reliable to predict the partition properties of the kind of compounds. For the atomic charge models, the molecular descriptors are molecular surface area(S), molecular shape(O), weight(M W), net charges on carboxyl group(Q OC), net charges of nitrogen atoms(Q N), and the most negative atomic charge(q -) of the solute molecule. For water solubility(log S W) and octanol/water partition coefficient(log K OW), the correction coefficients r 2 adj(adjusted for degrees of freedom) are 0.936 and 0.938, and the standard deviations are 0.364 and 0.223, respectively.
文摘Using density functional theory, noncovalent interactions and two mechanisms of covalent functionalization of drug carmustine with functionalized carbon nanotube（CNT） have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of drug carmustine with functionalized CNT is thermodynamically suitable. NTCOOH and NTCOCl can bond to the NH group of carmustine through OH（COOH mechanism） and Cl（COCl mechanism） groups, respectively. The activation energies, activation enthalpies and activation Gibbs free energies of two pathways were calculated and compared with each other. The activation parameters related to COOH mechanism are higher than those related to COCl mechanism, and therefore COCl mechanism is suitable for covalent functionalization. COOH functionalized CNT（NTCOOH） has more binding energy than COCl functionalized CNT（NTCOCl） and can act as a favorable system for carmustine drug delivery within biological and chemical systems（noncovalent）. These results could be generalized to other similar drugs.
基金TheNationalNaturalScienceFoundationofChina (No .2 9837180 )andtheResearchFoundationfortheDoctoralProgramofHigherEducationofChi
文摘The regression model for octanol/water partition coefficients ( K ow ), is founded with only two molecular descriptors available through quantum chemical calculations: solvation free energy (Δ G S ), and solvent accessible surface area (SASA). For the properties of 47 organic compounds from 17 types, the model gives a correction coefficient (adjusted for degrees of freedom) of 0 959 and a standard error of 0 277 log unit. It is a suitable way to predict the partition properties that are related to solute solvent interactions in the water phase.
基金financially supported by the National Natural Science Foundation of China(Nos.21707122 and 21677133)National College Students Innovation and Entrepreneurship Training Program(No.202010345069)。
文摘The distribution of organic compounds in stored lipids affects their migration,transformation,bioaccumulation,and toxicity in organisms.The storage lipid/water distribution coefficient(log K_(lip/w))of organic chemicals,which quantitatively determines such distribution,has become a key parameter to assist their ecological security and health risk.Due to the impossibility to measure K_(lip/w)values for a huge amount of chemicals,it is necessary to develop predictive approaches.In this work,a quantitative structure-property relationship(QSPR)model for estimating log K_(lip/w)values of small organic compounds was constructed based on 305 experimental log K_(lip/w)values.Quantum chemical descriptors and n-octanol/water partitioning coefficient were employed to characterize the intermolecular interactions that dominate log K_(lip/w)values.The hydrophobic and electrostatic interactions and molecular size have been found to play important roles in governing the distribution of chemicals between lipids and aqueous phases.The regression(R2=0.959)and validation(Q2=0.960)results indicate good fitting performance and robustness of the developed model.A comparison with the predictive performance of other commercial software further proves the higher accuracy and stronger predictive ability of the developed K_(lip/w)predictive model.Thus,it can be used to predict the K_(lip/w)values of cycloalkanes,long-chain alkanes,halides(with fluorine,chlorine,and bromine as substituents),esters(without phosphate groups),alcohols(without methoxy groups),and aromatic compounds.
文摘In this work a multi-objective quantitative structure-property relationship (QSPR) analysis approach was reported based on the study on three partition properties of 50 aromatic sulfur-containing carboxylates. Here multi-objectives (properties) were taken as a vector for QSPR modeling. The quantitative correlations for partition properties were developed using a genetic algorithm-based variable-selection approach with quantum chemical descriptors derived from AM1-based calculations. With the QSPR models, the aqueous solubility, octanol/water partition coefficients and reversed-phase HPLC capacity factors of sulfur-containing compounds were estimated and predicted. Using GA-based multivariate linear regression with cross-validation procedure, a set of the most promising descriptors was selected from a pool of 28 quantum chemical semi-empirical descriptors, including steric and electronic types, to integrally build QSPR models. The selected molecular descriptors included the net charges on carboxyl group (Q OC), the 2nd power of net charges on nitrogen atoms (Q 2 N), the net atomic charge on the sulfur atoms (Q S), the van der Waals volume of molecule (V), the most positive net atomic charge on hydrogen atoms (Q H) and the measure of polarity and polarizability (π), which were main factors affecting the distribution processes of the compounds under study. The statistically best QSPR models of six descriptors were simultaneously obtained by GA-based linear regression analysis. With the selected descriptors and the QSPR equations, mechanisms of partition action of the Sulfur-containing carboxylates were able to be investigated and interpreted.
