A drug’s acid breakdown reveals which possible changes actually happen

A computer-based chemical analysis distinguished likely degradation products from reactions too slow to occur during experiments.

Editorial illustration — not from the study.

The researchers developed an automated workflow that searches for chemical reactions without relying on a fixed list of reaction rules. It combines reaction discovery, energy-based filtering, quantum-chemistry calculations and simulations of how reaction rates change over time and temperature.

Applied to the acid-catalysed breakdown of BMS-644950, the workflow mapped 1,720 chemical species and 2,471 elementary steps before reducing the network to eight degradation products. It identified the two observed lactone products as dominant and proposed a tentative structure for a 466-da impurity reported previously.

Which products formed

The workflow found that several degradation products were thermodynamically favourable, meaning they could be energetically stable, but were unlikely to form on the experimental timescale. Their activation barriers were 36–40 kcal/mol, making the reactions too slow to observe under the conditions studied. Microkinetic simulations identified the two observed lactone products as the dominant products and proposed a tentative structure for the previously uncharacterised 466-da impurity. The full exploration finished within three days on a computing cluster.

Why reaction speed matters

Drug degradation studies need to identify products that can actually form during storage, processing or testing, rather than every product that is merely chemically possible. By including reaction speed as well as energetic favourability, this approach could help distinguish relevant degradation pathways from reactions that are too slow to matter under experimental conditions. The reported computing time also suggests that this type of automated modelling can be used for drug-like molecules at industrially relevant scales.

Evidence and caveats

This is a computational case study combining reaction-search calculations, quantum-chemistry refinement and microkinetic modelling for the acid-catalysed degradation of one active pharmaceutical ingredient, BMS-644950. The abstract reports agreement with two observed lactone products, while the structure proposed for the 466-da impurity is described as tentative. The abstract does not establish how well the workflow generalises to other drugs or conditions, nor does it report experimental confirmation of the proposed impurity structure.

Sediments show a Mexican lake recovering after decades of deforestation

Sediments and recent water samples show that Lago Verde underwent a major ecological shift during peak deforestation and erosion in the 1970s and 1980s. As forest cover partly recovered, disturbance-tolerant diatoms declined and some earlier planktonic species increased, but the lake has not fully returned to its former state.

15 hours ago·27 views

Materials & Energy

An AI system builds an open concrete database from 27,000 papers

Researchers developed an AI-powered pipeline that extracts information about concrete materials from scientific papers and organizes it into a database. Applied to a corpus screened from more than 27,000 publications, the system produced nearly 9,000 records for an open database on blended cement concrete.

3 days ago·43 views

Materials & Energy

Blinking nanocrystals help pinpoint particles to 1.2 nanometers

Researchers report that individual lanthanide-doped nanocrystals can blink collectively, even though each contains thousands of light-emitting ions. The long-lasting, high-contrast blinking enabled low-power microscopy that localized particles with a mean precision of 1.2 nanometers.

4 days ago·22 views