Abstract: The biological effects of metal-containing compounds are determined not only by the element dose and nominal composition but also by time-dependent changes in chemical identity, transport, and compartmentalization. Although metal species determination and transformation are well studied in bioinorganic chemistry, metallomics, and nanotoxicology, they are rarely considered as an integrated, evolving toxicological entity. Drawing on the chemistry of catalyst cocktails, we define dynamic toxicity as a time- and compartment-dependent effect that occurs when transformations of a metal-containing system alter the identity or number of its species and, consequently, the location, mechanism, or magnitude of the biological response. Metalloformulations based on Pt, Ru, and Au, as well as nanomaterials containing Ag, Cu, Zn, and Ni, illustrate trajectories involving ligand exchange, protein binding, particle dissolution, reprecipitation, corona remodeling, and intracellular redistribution. Depending on the system, toxicity may arise from the released molecular species, the parent particle, the surface chemistry, or a combination of these; thus, ion release is not a universal explanation. We organize experimental strategies around four interdependent parameters: chemical identity, spatial localization, temporal evolution, and biological response, while accounting for measurement-induced perturbations. Single-atom catalysts and nanozymes represent a novel test case, in which efficacy and toxicity can depend on the preservation or transformation of atomically dispersed sites. This concept links established observations from multiple disciplines and provides operational criteria for the mechanistically based evaluation and development of metal-containing drugs, catalysts, and nanomaterials.

Cite: Galushko A.S. , Egorova K.S. , Shaydullin R.R. , Ananikov V.P.
Dynamic toxicity of metal-containing systems: Biological effects emerge from evolving metal cocktails
Coordination Chemistry Reviews. 2026. V.568. 218426 . DOI: 10.1016/j.ccr.2026.218426 WOS Scopus OpenAlex

Dates:

Submitted:	Jun 5, 2026
Accepted:	Aug 12, 2026
Published print:	Aug 17, 2026
Published online:	Aug 17, 2026

Identifiers:

≡ Web of science:	WOS:001852164800001
≡ Scopus:	2-s2.0-105047739317
≡ OpenAlex:	W7203643829

Altmetrics: