Not all chemists wear white coats: computational organic chemistry

Introduction

'Not all chemists wear white coats,' aptly describes the newest pillar of chemical research. Coined by the Royal Society of Chemistry, computational modelling has become an essential tool across all areas of traditional chemistry. As artifical intelligence (AI) and machine learning become increasingly prevalent in research, the future of chemistry may unfold computationally before ever touching a test tube. Given the breadth of the field, this article will focus specifically on computational advancements in organic chemistry.

Analytical Chemistry

Density Functional Theory (DFT) is a quantum computational method that models molecules based upon the distribution of their electron density. It can be utilised by organic chemists to determine the stereochemistry of a product by modelling Vibrational Circular Dichroism spectra (VCD).

VCD is a spectroscopic technique which measures the difference in absorption of left versus right-handed circularly polarised light by chiral molecules. By using DFT to compute the VCD spectra of each enantiomer, chemists can compare them to experimental spectra. A match between the compound and the experimental spectrum indicates an accurate assignment of the molecule’s stereochemistry. See Figure 1.

Predicting molecular conformation

While the Cahn-Ingold-Prelog naming system allows chemists to describe the 3D arrangement of a molecule, computational analysis can help predict which molecular shape is preferred in practice. Molecular Mechanics (MM) is a computational method that treats molecules using classical physics, modelling atoms and bonds as ‘balls’ connected by ‘strings’. A force field is used to calculate the potential energy of a molecule, accounting for bond stretching, angle bending, bond rotation, van der Waals interactions and electrostatic forces.

A simple example of how this method supports organic chemistry is the determination of the most stable conformation of butane. By rotating the central C-C bond through 360°, the energy of each conformation can be plotted against the dihedral angle. This analysis shows that the anti-conformation is the most stable, as the two methyl groups are positioned 180° apart to minimise steric strain. See Figure 2.

Drug discovery

Computational chemistry has also transformed drug discovery by enabling chemists to simulating how potential drug compounds will bind to their target active site. In the past, drug development has often relied on synthesising a large number of candidates and testing each experimentally to see which worked. Today, advances in computational chemistry, combined with X-ray crystallographic data, allows both a drug candidate and its protein binding site to be modelled before any lab work begins. This helps researchers save both time and resources.

Known as structural based drug design, this approach commonly relies on hybrid computational methods, particularly Quantum Mechanics/ Molecular Mechanics (QM/MM). In this case, the chemically active regions, such as the drug molecule and protein active site are treated using QM while the rest of the proteins is treated using MM. By combining these techniques, a balance is struck between computational accuracy and calculation time, especially important for larger molecules. See Figure 3.

Conclusion

In conclusion, computational chemistry is an essential tool for interpreting experimental results and generating new scientific insight. While this article has focused on its role in supporting organic chemistry research, the reach of computational chemistry extends far beyond this field. From modelling batteries and solid state materials to organometallic catalysis, computational chemistry is now firmly embedded in modern chemical research.

Written by Antony Lee

Related articles: Quantum- chemistry, computing

REFERENCES

The Royal Society of Chemistry - https://edu.rsc.org/resources/not-all-chemists-wear- white-coats/1654.article (Accessed January 2026)

Y.L. Zeng, X.Q. Huang, C.R. Huang, H. Zhang, F. Wang, Z.X. Wang, Angew. Chem. Int. Ed., 2021, 60, 10730-10735

Chemistry LibreTexts https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_%28Mor sch_et_al.%29/03%3A_Organic_Compounds_Alkanes_and_Their_Stereochemistry/3.07% 3A_Conformations_of_Other_Alkanes (Accessed January 2026)

Ecole des Bio-Industries - https://www.ebi-edu.com/en/coup-de-coeur-research-9/ (Accessed January 2026)