Stereochemistry

SMILES can also encode stereochemistry

Tetrahedral Centers: Chirality at a tetrahedral center is indicated using @ (counter-clockwise) or @@ (clockwise). 

The rule is: looking from the first neighboring atom towards the chiral atom, the other three neighbors are listed in either clockwise or counterclockwise order. 

The chiral atom and its attached hydrogen must be in square brackets, e.g., [C@H].

Double Bonds: Geometric isomerism (E/Z) around a double bond is specified with / and . For trans-2-butene, the SMILES is C/C=C/C. For cis-2-butene, it's C/C=C\C.

Tetrahedral chirality (R / S style)

1. (R)-2-Butanol and (S)-2-Butanol (Figure 1)

SMILES:

• (R)-2-butanol (example): C[C@@H](O)CC

• (S)-2-butanol (example): C[C@H](O)CC

Code:

rbutanol=Chem.MolFromSmiles("C[C@@H](O)CC")

rbutanol

sbutanol=Chem.MolFromSmiles("C[C@H](O)CC")

sbutanol

2. Double-bond (E/Z) stereochemistry

2-Butene — trans (E) vs cis (Z)

• trans (E) 2-butene: C/C=C/C (Figure 2)

• cis (Z) 2-butene: C/C=C\C

Code:

transbutene=Chem.MolFromSmiles("C/C=C/C")

transbutene

cisbutene=Chem.MolFromSmiles("C/C=C\\C") ## note the escaping backslash in Python string

cisbutene

You've successfully taken your first steps with RDKit! You learned how to create, visualize, and analyze a molecule programmatically. This is the foundation of cheminformatics and opens the door to more advanced topics like molecular similarity, clustering, and even machine learning for predicting molecular properties.

You can access the Google Colab here; it contains all the code used in this tutorial: Google Colab

REFERENCES

• Chetry, A.B., Ohto, K. From molecules to data: the emerging impact of chemoinformatics in chemistry. J Cheminform 17, 121 (2025). https://doi.org/10.1186/s13321-025-00978-6 .

• Cox PB, Gupta R. Contemporary Computational Applications and Tools in Drug Discovery. ACS Med Chem Lett. 2022 Jun 1;13(7):1016-1029. doi: 10.1021/acsmedchemlett.1c00662. PMID: 35859884; PMCID: PMC9290028. 

• Daylight Theory Manual — SMARTS and SMILES (patterns/specification): http://www.daylight.com/dayhtml/doc/theory/theory.smarts.html 

• Landrum, G. (2013). RDKit: Open-source cheminformatics. http://www.rdkit.org.

• Neovarsity - Cheminformatics: An In-depth Guide for Beginners.

• PatWalters practical_cheminformatics tutorials

• RDKit Official Website: https://www.rdkit.org/

• The RDKit Documentation: https://www.rdkit.org/docs/index.html

• The RDKit Book: https://www.rdkit.org/docs/RDKit_Book.html - A comprehensive resource for diving deeper.

• Weininger, D. (1988). SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. Journal of Chemical Information and Computer Sciences, 28(1), 31–36. 

• Xu J, Hagler A. Chemoinformatics and Drug Discovery. Molecules. (2002) Aug 30;7(8):566–600. doi: 10.3390/70800566. PMCID: PMC6146447.