Organometallic compounds contain organic and metallic molecules, with at least one bond between a carbon atom (contained in an organic compound) and a metal. Metals in organometallic compounds include transition metals, alkaline earth, and alkali metals.
Recently, organometallic compounds have emerged as useful materials in medicine due to their novel physiochemical properties. They have seen increasing applications for the treatment of a variety of diseases and medical conditions. This article will look at how organometallic compounds are applicable in the field of drug delivery and discovery.
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Organometallic Compounds: Foundations and Impact
Organometallics are a large class of compounds in chemistry. Over the past few decades, they have played an increasingly important role in biomedicine and the life sciences.
Their main use in life sciences and other industries is as catalysts and intermediates in industrial and laboratory processes.1 As mentioned above, they are composed of a carbon-containing organic compound and a metal, with the metal bonded to a carbon atom in the organic compound, hence organometallic.
Several organometallic compounds, such as ferrocene, have been developed over the decades since their initial development. This highly stable organometallic compound comprises an iron atom sandwiched between two hydrocarbon rings.
Types of organometallic compounds include coordination, ionic bonded, and σ – bonded organometallic compounds.
Organometallic compounds are synthesized via several routes, including halogen-metal exchange, reactions between metals and organic halides, preparation from acidic hydrocarbons, displacing less electropositive with more electropositive metals, and preparation from polyhalogen compounds.2
Organometallic compounds have profoundly impacted the world of medicine and have emerged as useful compounds in drug discovery and delivery in recent years. This is due mostly to their unique physiochemical properties, such as stability, reactivity, and the ability to form diverse coordination complexes.
N-(3-aminopropionyl)-L-histidanto zinc, for instance, has been used in Japan in the treatment of peptic ulcers, and animal models have shown that this organometallic complex has anti-inflammatory properties.
Alongside this drug, other zinc-based complexes and solver nanoparticles have exceptional anti-inflammatory properties, which make them targets for organometallic drug development.3
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Applications of Organometallics in Drug Delivery
Organometallic compounds can provide some potential benefits as drug delivery systems. They can enhance drug stability, solubility, and bioavailability. Furthermore, due to their unique electronic and chemical properties, they can be highly tailored for specific drug delivery applications.
In drug delivery, the main goal is the efficient and targeted delivery of therapeutics to disease sites without harmful side effects. Organometallic compounds have several properties that make them ideal for this medical application, such as tunable redox potentials, unique reactivity profiles, and ligand exchange kinetics.4
Intense research is being conducted on using these compounds for targeted drug delivery applications. Scientists are exploring incorporating them into nanoscale carriers such as micelles and liposomes.
Furthermore, organometallic compounds are being functionalized with biocompatible ligands to improve their use as drug delivery systems.
Integrating organometallics into drug delivery systems could revolutionize medicine, improving the patients' therapeutic outcomes worldwide.
Applications of Organometallics in Drug Discovery
As well as potential novel drug delivery systems, organometallics have also found application in drug discovery due to their emerging use as anticancer agents, antimicrobial agents, and enzyme inhibitors.
Recent decades have seen the development of several novel drugs based on organometallics, such as anticancer catalytic drug candidates. Organometallic complexes such as Os(II) complexes, Ir(III) complexes, and Ru(II) complexes have emerged as effective cancer-killing drugs.
Organometallics are highly effective at catalyzing several reactions, which has made them interesting candidates for these applications.5
Organoarsenicals are organometallic drugs safer than aminophenyl arsenic acid. They have been used to treat African trypanosomiasis, otherwise known as sleeping sickness, since the early 20th century.
Recent research has investigated the use of ferrocene-containing drug candidates which display antitumor and antiparasitic activity.
Currently, a number of these drugs and other organometallic complexes are under study at various stages of clinical trials.
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Challenges in Using Organometallics for Drug Applications
However, despite promising progress in the study of organometallics for medical applications, some key hurdles must be overcome if widespread adoption is to be seen in the fight against disease.
The synthesis of these compounds is a multi-step process with several issues at each stage.
For example, problems with competitive coordination abilities due to the structure of some ligands can cause technical challenges during drug discovery and development.3 Moreover, problems can occur with the crystallization of insoluble compounds.
Additionally, researchers have reported several problems with the adhesion of metallic compounds to organic ones, but these can be overcome by surface modification processes such as partial oxidation.
Other challenges include the toxicity of certain metals, which is an obvious drawback when designing new drugs, as any therapy must have minimal toxicity. Furthermore, regulatory hurdles impede the development of new organometallic compound-based drugs and therapeutics.
However, various strategies can overcome several current challenges in this emerging field of drug discovery and development.
These include improved synthetic methods, thorough preclinical evaluations of potential compounds, and designing more biocompatible compounds.
Future Directions for Organometallics in Drug Applications
The design of drugs based on organometallic compounds and novel organometallic drug delivery systems can benefit greatly from future trends toward interdisciplinary approaches combining organometallic chemistry, pharmacology, and materials science.
Furthermore, emerging trends such as AI and machine learning, the integration of computational modeling, advanced synthesis and synthetic approaches, and high-throughput screening for novel therapeutics targets can benefit the future direction of organometallic research over the coming years.
In Summary
Organometallics are a class of compounds that has existed since the 19th century, but they have the potential to revolutionize drug discovery, drug delivery, and therapeutics development, improving clinical outcomes for patients worldwide with various medical conditions and diseases.
However, some fundamental challenges persist. To develop safe, non-toxic, and efficacious drugs and drug delivery systems with good bioavailability, researchers will need to leverage continued innovation and research to harness the full potential of this class of compounds.
References
- Shriver, D.F (2022) Organometallic compound [online] Encyclopedia Britannica. Available at: https://www.britannica.com/science/organometallic-compound (Accessed on 14 August 2024)
- Roberts, J.D & Caserio, MC [online] 14.11.1: Preparation of Organometallic Compounds LibreTexts Chemistry. Available at: https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/ (Accessed on 14 August 2024)
- Szczepaniak, A & Fichna, J (2019) Organometallic Compounds and Metal Complexes in Current and Future Treatments of Inflammatory Bowel Disease and Colorectal Cancer—a Critical Review Biomolecules 9(9) 398. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770552/ (Accessed on 14 August 2024)
- Zhang, X et al. (2024) Organometallics for Drug Delivery and Drug Discovery Applications Frontiers in Drug Delivery [online] Available at: https://www.frontiersin.org/research-topics/60591/organometallics-for-drug-delivery-and-drug-discovery-applications (Accessed on 14 August 2024)
- Ong, Y.C & Gasser, G (2020) Organometallic compounds in drug discovery: Past, present and future Drug Discovery Today: Technologies 37 pp. 117-124. [online] ScienceDirect. Available at: https://www.sciencedirect.com/science/article/abs/pii/S1740674919300010 (Accessed on 14 August 2024)
Further Reading
Advancing Cardiovascular Drug Discovery: Translational Framework Leverages Genetic and Proteomic Insights