A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead Original paper

What was reviewed?

This paper reviewed how thiol-containing chelating agents bind and help remove three high-priority toxic metals—mercury, cadmium, and lead—from the body. The authors connected clinical practice to coordination chemistry by explaining how sulfhydryl (thiol) groups interact with Hg²⁺, Cd²⁺, and Pb²⁺, and why those binding preferences matter for treatment success. The review compared classic and newer chelators, including BAL (dimercaprol), DMSA (succimer), DMPS (unithiol), d-penicillamine, alpha-lipoic acid and its reduced form (DHLA), and emerging candidates such as MiADMSA, while also discussing pharmacokinetics, toxicity, and practical drug selection.

Who was reviewed?

The review synthesized evidence drawn from human poisoning and overexposure cases (including occupational exposure), supported by animal and in-vitro work that clarifies tissue distribution, excretion pathways, and metal–ligand equilibria. It also integrated laboratory chemistry studies (speciation, stability constants, and structural approaches such as spectroscopy and modeling) to explain why certain chelators perform better for specific metals or exposure forms.

What were the most important findings?

The review aligned drug choice with metal form and target tissue, emphasizing that DMSA is generally preferred for lead poisoning and organic (methyl) mercury exposure due to a better safety profile than older agents, while DMPS is positioned as the preferred option for acute inorganic mercuric salt poisoning. The authors highlighted recurring constraints that shape real-world outcomes: most thiol chelators distribute mainly outside cells and have limited ability to cross the blood–brain barrier, which restricts removal of brain mercury and intracellular cadmium stores. They also underscored clinically relevant tradeoffs, including that DMPS use can coincide with losses of essential trace elements such as zinc and copper, which supports monitoring and replacement during therapy. From a microbiome database standpoint, the key “signal” is absence of direct microbiome data: the review flags gut-related variables (like oral absorption and fecal/biliary excretion) as clinically meaningful, but it does not map those variables to specific microbial shifts.

What are the greatest implications of this review?

Clinicians can use this review as a decision-support bridge between mechanism and bedside chelation choice: match the chelator to the metal species and exposure route, and anticipate limitations in mobilizing intracellular or CNS stores. The chemistry framing helps explain why dithiol agents (like DMSA and DMPS) often outperform single-thiol ligands for these metals, and why combination approaches get proposed when deposits sit in hard-to-reach compartments—yet the authors are clear that clinical experience with combinations remains limited. For microbiome-aware practice, the implication is practical rather than taxonomic: because chelation depends partly on gastrointestinal handling and excretion, gut function may influence exposure and elimination, but this paper cannot populate microbiome signature fields beyond noting that no MMA were reported.