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 LD₅₀^CN(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.