Theoretical Study Of Bio-toxicity Of Thiobenzene-containing Derivatives And Heterocyclic Nitrogen Compounds

Quantitative structure-property relationships（QSPR） and quantitative structure-activity relationships（QSAR） study has become a cutting edge field in the subjects of theoretical chemistry. Therefore, via analyzing and learning their change laws betweenmolecular structure descriptors and phisico-chemical properties or biological character,building models between molecular structure descriptors and their properties biological character, we can easily explain and predict their properties or biological charactertheoretically. So, to find the appropriate quantum chemical parameters which can efficiently reflect the molecular properties is the key.29thiobenzene-containing derivatives were researched in this paper, molecular mechanics and semi-empirical quantumchemistry RM1methods were used to refine and optimize their geometry and thena series of quantum chemical parameters were extracted from the geometric model.QSAR model were established between quantum chemical parameters and their biological toxicity of thiobenzene-containing derivatives to photobacteria. In terms of heterocyclic nitrogen compounds, the geometry of this kinds of compounds were fully optimized and quantum calculated at the density functional theory（DFT）/B3LYP level oftheory with the6-311+G（d） basis set, then add the heavy atom polarization, recognize the resulting configuration was stable structure. The models were built in this study with good stability and predictive ability, according to QSAR model, it is helpfulfor new molecular designation and bio-toxicity prediction in terms of biological toxicity of thiobenzene-containing derivatives to photobacteria and biological toxicity of heterocyclic nitrogen compounds to Daphnia magna Straus. This work mainly focuson the follows:1．Geometry optimization and quantitative calculationThrough quantum chemistry calculation, then extracting the very important parameters in QSAR studies from the output file: Energy of highest occupied molecularorbital（HOMO）E_HOMO，Energy of lowest unoccupied molecular orbital(E_LUMO)，frontier orbital energy gap ΔE(E_LUMO-E_HOMO)，absolute hardness（η），electronegative（χ）,electrophilicity index（ω），polar surface area（PSA）, number of hydrogen-bond donors（HBA）, total molecular energy（E_T）, polar surface area（PSA）, molecular volume V.Thermodynamic parameter：internal energy（Eth）、heat at constant volume（CV）、entropy（S）、total energy（E_T）、enthalpy（H°）、free energy（G°）、zero-point vibration energy（ZPVE）and polarizability （α） and so on.2．Selecting parameters and established QSAR modelsIn this paper, the models were built with a method of multiple linear regressionby using high correlation quantum chemical parameters which was objective, accurate, vivid and with specific meaning in explaining mechanism as independent variables, and toxic parameter lg （1/EC50） such as thiobenzene-containing derivatives’ bio-toxicity to photo bacteria and Daphnia magna Straus a s dependent variable. The processof building QSAR models strictly follows the rules of mathematical statistics, the stability and reliability of models were checked and testified by significant analysis finally.3. Validation and explanation on QSAR modelRandom sampling prediction（RSP） and leave-one-out cross-validation（LOO-CV） method were used to testify the stability and predictive ability of the models, residualanalysis were adopted between experimental values and predictive values. The results show that the model is steady, reasonable and effective. The results of this study are as follows:（1） Thiobenzene-containing: The results indicate that biological toxicity of thiobenzene-containing derivatives to photo bacteria was affected obviously by frontier orbital energy gap ΔE(E_LUMO-E_HOMO), Octane/Water partition coefficients（lgKow）, hammett charge effect constant（Σσ）, electrostatic of C（6） as well as total electrostatic of benzene ring（ΣE）. At a result, we establish a QSAR model(Lg（1/EC50）=10.238-0.009△E+3.034E（6）+2.108ΣE-0.292lgK_OW+0.522Σσ,R=0.930)with satisfactory results.（2） Heterocyclic nitrogen compoundsThe results show that biological toxicity of heterocyclic nitrogen compounds toDaphnia Magna Straus was affected obviously by frontier orbital energy gap ΔE(ELUMO-E_HOMO, Octane/water Partition Coefficients（lgKow）, Most positive charged atom（q⁺）. At a result, we establish a QSAR model lg（1/EC50）=4.18+3.735q^-+0.973lgK_ow+0.007ΔΕ with satisfactory results.