Theoretical modeling of structure-toxicity relationship of cyanides.

The global descriptors of chemical activity: ionization potential IP, electron affinity EA, chemical potential μ, absolute electronegativity χ, molecular hardness η and softness S, electrophilicity index ω for cyanides X(CN)k with X=H, Na, K, Ag, Cu, Ca, Hg, Cd, Zn in the gas phase and water medium have been determined by taking advantage of the quantum-chemical computations. To this aim, the HOMO and LUMO energy levels were calculated using DFT B3LYP method and QZVP (Valence Quadruple-Zeta Polarization) basis set, which enables precise calculations for hydrogen cyanide and its salts containing both light (H, Na, Ca) and heavy (K, Ag, Cu, Cd, Hg, Zn) atoms. The results obtained indicate that while the EA-parameter roughly determines the LD50 values for the cyanides considered, the ω-descriptor is related rather to the product of cyanide LD50 and hydrolysis n-degree. Hence, the theoretical LD50CN(ω) function proposed is interconnected with the n⸳LD50 collective variable, whereas LD50(EA) directly approximates LD50 values indicating that the toxicity of cyanides decreases with increasing EA, ω-values. The calculations carried out suggest that some of the LD50(Exp) experimentally determined are incorrect (AgCN) or inaccurate (Cd(CN)2) and require revision. Comparison of the theoretically estimated LD50(ω) with NOAEL toxicity parameters indicates that they are well correlated ​​in contrast to LD50(EA)​​ and LD50(Exp),​​ exhibiting lower and marginal degrees of correlation, respectively.