N-heterocyclic carbene metal complexes as therapeutic agents: a patent review

ABSTRACT

Introduction

Besides the well-established catalytic, synthetic and materials related applications of N-heterocyclic carbene (NHC) metal complexes, their use as therapeutics deserves a special attention. Many literature reports indicate that their bioactivity is superior to other organometallic compounds. The main focus of patent disclosures in this area is the elucidation of anticancer and antimicrobial activities of NHC transition metal complexes. Nonetheless, a variety of other biological activities have been reported in non-patent literature to date.

Area covered

Patent literature on NHC metal complexes with focus on their therapeutic applications and relationship structure-biological activity disclosed since the first issued patent (2010) up to now (2021). The information was collected from publicly available data sources (e.g. Chemical Abstracts, MedLine, Reaxys, and SciFinder).

Expert Opinion

Although the first reports on biological applications of NHC metal complexes originate in 2000s, the greatest progress in this area was made only in the past decade. A growing number of patent disclosures indicates that structural design of new NHC metal complexes is crucial for their successful use in both medicine and biochemistry. In the next few years, we expect to see more stable and effective NHC metal complexes as potential therapeutic agents and perhaps in clinical trials.

KEYWORDS:

• N-heterocyclic carbenes
• NHC metal complexes
• anticancer activity
• cisplatin
• antimicrobial activity
• pathogens
• minimal inhibitory concentration

Article highlights

• Besides many other applications, structurally diverse stable N-heterocyclic carbene metal complexes are potent therapeutic agents.

• Anticancer and antimicrobial activities of NHC metal complexes are the most studied in patent literature; however, their applications in radiolabeling, bioprobing, and amino acid mimicking have also been reported.

• Gold and platinum, and less common iridium and palladium mono- and bimetallic NHC complexes are highly efficient against several cancer cell lines. Their structures mostly contain metallocycles, chelates that are coordinated to imidazole-2-ylidenes often stabilized by sterically hindered substituents.

• Silver complexes of imidazole-2-ylidenes or their gels with glutathione are more effective antibiotics than their imidazolium salt precursors. However, their activity is either comparable with silver nitrate or even lower. The less studied platinum and rhenium NHC complexes have not displayed excellent antimicrobial activity, but are promising for future studies.

• The discovery of stable NHC complexes with non-precious metals and optimized ligands for therapeutic use should lead to rapid development of the field in the future and clinical trials.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Georgia State University, Jain University, Rosalind Franklin University, and Florida Gulf Coast University for support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded by any federal agency.