# Transformer-Based Approach for Automated Functional Group Replacement in Chemical Compounds

arXiv: https://arxiv.org/abs/2601.07930 · HTML: https://mlsanity.com/paper/2601.07930/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 4 of its 16 references that are in the map.
- First posted on arXiv 12 Jan 2026.

## Builds on (most cited first, 4 of 4)

- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [Unifying Molecular and Textual Representations via Multi-task Language Modelling](https://mlsanity.com/paper/2301.12586/) (2023)
- [Learning Multimodal Graph-to-Graph Translation for Molecular Optimization](https://mlsanity.com/paper/1812.01070/) (2018)
- [Decoder-Only or Encoder-Decoder? Interpreting Language Model as a Regularized Encoder-Decoder](https://mlsanity.com/paper/2304.04052/) (2023)

## Abstract (arXiv)

Functional group replacement is a pivotal approach in cheminformatics to enable the design of novel chemical compounds with tailored properties. Traditional methods for functional group removal and replacement often rely on rule-based heuristics, which can be limited in their ability to generate diverse and novel chemical structures. Recently, transformer-based models have shown promise in improving the accuracy and efficiency of molecular transformations, but existing approaches typically focus on single-step modeling, lacking the guarantee of structural similarity. In this work, we seek to advance the state of the art by developing a novel two-stage transformer model for functional group removal and replacement. Unlike one-shot approaches that generate entire molecules in a single pass, our method generates the functional group to be removed and appended sequentially, ensuring strict substructure-level modifications. Using a matched molecular pairs (MMPs) dataset derived from ChEMBL, we trained an encoder-decoder transformer model with SMIRKS-based representations to capture transformation rules effectively. Extensive evaluations demonstrate our method's ability to generate chemically valid transformations, explore diverse chemical spaces, and maintain scalability across varying search sizes.