Medicinal Chemistry: The Science of Drug Discovery

Oct 19, 2022 | SCIENCE, Chemistry

Medicinal Chemistry Uses Boron Clusters

Medicinal chemistry is the branch of chemistry concerned with designing, synthesizing, and discovering new drugs. It is a highly interdisciplinary field that develops and synthesizes new molecules using unique molecules of carborane. These carborane clusters are used as boron delivery agents for cancer therapy and anti-infection.

Medicinal chemistry

Medicinal chemistry


Carboranes are a class of organometallic compounds that contain carbon, hydrogen, and boron. These boron clusters have a general formula of C2BnHn + 2 (n ranges from 3-10) and find numerous potential applications in medicinal chemistry

The first carboranes were developed during the 1950s, but the results were not released until 1962-63. Since then, many carboranes have been developed and merged with transition metals to produce metallacarboranes. A few of these metallacarboranes have catalytic activity. 

Structure of Carborane Clusters

Carborane clusters and polyhedral boranes have electron delocalization (non-classical bonding), indicating that there are not enough valence electrons for bond formation in the 2c2e pair (2-center-2-electron) and, therefore, form 3c2e bonds (3-center-2-electron). These bonds then create trigonal faces and hypercoordination. 

The high connectivity of atoms in a cluster adjusts for the fairly low electronic structure in skeletal bonds, which is why these structures are often drawn without denoting the atoms at every vertex. The three-dimensional deltahedral shapes are formed by the boron and carborane clusters.

Wade described the clusters in the closo polyhedral forms, where n indicates the boron atoms comprising n + 1 skeletal bonding electron pairs, leading to anions of the type closo-[BxHx]2- (x = 6 to 12 and above).

Due to their delocalized electron water-repellent surface, carboranes are highly reflective of inorganic compounds such as benzene rings and 3-D aromatic rings. The two carbon atoms inside a cage enable the involvement in substitution reactions without deterioration, which is its most important factor since it can enter into various types at both boron and carbon atoms without degrading the carborane cage. 

Icosahedral Dicarbadodecaborane

The most common polyhedral borane in medicinal chemistry is icosahedral dicarbadodecaborane (C2B10H12). Scientists discovered this carborane nearly fifty years ago, which takes up significantly more space than benzene rings or adamantine.

Icosahedral carboranes are symmetrical or globular molecules with 1.8 angstroms (Å) long B-B and C-B bonds with 12 vertices. These polymers are connected by covalent (2c-2e) bonds formed by Cc or B atoms. Provided the hydride identity of the H atoms in the B-H vertices, these clusters can produce 3c-2e bonds. The coordination of polymers to icosahedral boron clusters is significant in potential applications and structural chemistry. 

The hybrid polymers that combine icosahedral boron clusters miniaturize the devices while increasing efficiency, reliability, and ease of use. This is great news for electronics and semiconductors sectors requiring extra technical advanced materials.

Boron Cluster Properties for Medicinal Chemistry

Boron clusters have distinct properties that make them ideal for drug discovery in medicinal chemistry applications. 

  • They can form non-covalent interactions with various molecules, such as ionic interactions, σ-hole bond formation, and dihydrogen bonding that differ from pure organic compounds due to the interaction with biologically active compounds.
  • They can create 3D molecules due to their spherical or ellipsoidal topography and 3D arrangement.
  • They are resistant to ionizing radiation, which is required to develop radiopharmaceutical drugs.
  • They are chemically stable while also being vulnerable to functionalization.
  • They are less prone to metabolism and are more stable in a biological environment.
  • Amphiphilicity, hydrophilicity, or lipophilicity can alter the boron clusters’ pharmacokinetics and bioavailability depending upon which cluster is utilized.
  • They have a high boron content in the cluster, which is essential for exploring its potential applications for boron neutron capture therapy.

These diverse properties of boron clusters have made them one of the most studied classes in medicinal chemistry. Among the best are carboranes with cage-structured boron molecules. Furthermore, dodecaborate anion and coordination compounds of various sizes and cage-structural geometries (metallaboranes and metallacarboranes) are also important in medicinal chemistry. 

Boron clusters have highly desirable biological properties and abiotic nature, indicating biologic and chemical orthogonality to instinctive cellular components and resistance to catabolism.

The Importance of Boron Clusters in Medicinal Chemistry

Due to the potential of boron clusters to impact a lipid membrane and strong adhesion to the hydrophobic region of common cyclodextrins, it is clear that ionic compounds will impart water solubility and penetrate cell membranes. 

This penetration behavior is needed for any drug to reach its target. Several studies have demonstrated the solubility of such compounds in a water-repellant environment. Genady et al. successfully proved that a fluorescent dye could invade and acquire in the cell membranes of mammalian cells.