OPTIMAL NANO-DESCRIPTORS AS TRANSLATORS OF ECLECTIC

DATAINTO PREDICTION OF THE CELL

MEMBRANE DAMAGE BY MEANS

OF NANO METAL-OXIDES

ALLA P. TOROPOVA & ANDREY A. TOROPOV & EMILIO BENFENATI & RAFI KORENSTEIN & DANUTA LESZCZYNSKA &

JERZY LESZCZYNSKI

Environ Sci Pollut Res (2015) 22:745–757

Acknowledgments:

The authors are grateful to the

EU FP7 project PreNanoTox (contract 309666).

SYSTEMATIZATION OF KNOWLEDGE ON NANOMATERIALSHAS BECOME A NECESSITY WITH THE FAST GROWTH OF APPLICATIONSOF THESE SPECIES. BUILDING UP PREDICTIVE MODELS THAT DESCRIBEPROPERTIES (BOTH BENEFICIAL AND HAZARDOUS) OF NANOMATERIALS ISVITAL FOR COMPUTATIONAL SCIENCES. CLASSIC QUANTITATIVE STRUCTURE–PROPERTY/ACTIVITY RELATIONSHIPS (QSPR/QSAR) ARE NOT SUITABLE FOR INVESTIGATING NANOMATERIALS BECAUSE OF THE COMPLEXITY OF THEIR MOLECULAR ARCHITECTURE. HOWEVER, SOME CHARACTERISTICS SUCH AS SIZE, CONCENTRATION, AND EXPOSURE TIME CAN INFLUENCE ENDPOINTS (BENEFICIAL OR HAZARDOUS) RELATED TO NANOPARTICLES AND THEY CAN THEREFORE BE INVOLVED IN BUILDING A MODEL. APPLICATION OF THE OPTIMAL DESCRIPTORS CALCULATED WITHTHE SO-CALLED CORRELATION WEIGHTS OF VARIOUS CONCENTRATIONS ANDDIFFERENT EXPOSURE TIMES ARE SUGGESTED IN ORDER TO BUILD UP APREDICTIVE MODEL FOR CELL MEMBRANE DAMAGE CAUSED BY A SERIESOF NANO METAL-OXIDES. THE NUMERICAL DATA ON CORRELATIONWEIGHTS ARE CALCULATED BY THE MONTE CARLO METHOD. THE OBTAINEDRESULTS ARE IN GOOD AGREEMENT WITH THE EXPERIMENTALDATA.

THE EXPERIMENTAL DATA ON CELLMEMBRANE DAMAGEMEASURED BY PROPIDIUM IODIDE (PI) UPTAKE ARE TAKEN FROM THE LITERATURE, WHICH ALSO REPORTS 24 NANO METAL-OXIDES(ZRO2, ZNO, YB2O3, Y2O3, WO3, TIO2, SNO2, SIO2, SB2O3, NIO, NI2O3, MNO3, LA2O3, IN2O3, HFO2, GD2O3, FE3O4, FE2O3, CUO, CR2O3, COO, CO3O4, CEO2, AL2O3). THE NUMERICAL DATA ON THIS ENDPOINT RELATED TO FOUR DOSES (50, 100, 150, AND 200 ΜG/ML) AND SEVEN EXPOSURE TIME (FROM 1 TO 7 H) FOR ALL 24 NANO METAL-OXIDES ARE EXAMINED. IN FACT, THE PERCENTAGE OF CELLS WHICH HAVE MEMBRANE DAMAGE IS THE MEASURE OF IMPACT OF NANO-OXIDES (FOR DEFINED DOSE AND EXPOSURE TIME).

QUASI-SMILES FOR REPRESENTATION OF IMPACT OF NANO-FE3O4 UPON CELL MEMBRANE, WHERE DOSE IS 200 ΜG/ML (“A”) AND EXPOSURE TIME IS 5 H (“5”)

THE LIST OF CKWHICH ARE USED FOR REPRESENTATIONOF NANO METALOXIDESAND CONDITIONS OFTHEIR ACTING. FOR EXAMPLE,THE “ZN.O.A2” MEANS (I)NANO METAL-OXIDE ZNO,(II) DOSE IS 200 ΜG/ML,AND (III) EXPOSURE TIME IS 2 H

HAVING DATA ON OPTIMAL CORRELATION WEIGHTS, ONE CAN:(I) CALCULATE DCW(T,NEPOCH) FOR ALL NANOMETAL-OXIDES;(II) CALCULATE (WITH DATA ON THE TRAINING SET) A MODEL FOR CELL MEMBRANE DAMAGE (CMD)

AND (III) CHECK UP THE PREDICTIVE POTENTIAL OF THE MODEL USING THE EXTERNAL VALIDATION SET.

The T and Nepoch are parameters of the optimization:the T is threshold, i.e., the coefficient for classification of CAk into two categories: rare and not rare. The correlation weight for rare impact is set as zero, so this component is not involved in a model. The Nepoch is the number of epochs of the Monte Carlo optimization. The computational experiments with the CORAL software have shown that as a rule, for an endpoint preferable, T* and N*epoch can be extracted after analysis of a range of the T (e.g., from 1 to 10) and analysis of a range of Nepoch (e.g., from 1 to 100).

THE SCHEME OF CALCULATION OF PREFERABLE VALUES T* AND N*EPOCH

… … … … …… … … ..

THE CELL MEMBRANE DAMAGE BY MEANS OF NANO METAL-OXIDES IS A COMPLEX FUNCTION OF MANY FACTORS BESIDES CHEMICAL COMPOSITION, DOSE, AND EXPOSURE TIME. HOWEVER, THE COMPARISON OF FIVE MODELS, WHICH ARE BUILT UP FOR DIFFERENT DISTRIBUTION INTO THE VISIBLE TRAINING SET AND INVISIBLE VALIDATION SET INDICATES THAT CHEMICAL COMPOSITION, DOSE, AND EXPOSURE TIME CAN BE A BASIS TO PREDICT THE ENDPOINT USING THE MONTE CARLO METHOD.

Conclusions:

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