Reviews & Analysis

A decade ago, Zaworotko and co-workers engaged the principles of crystal engineering to demonstrate that narrow-pore (<0.7 nm) coordination networks are ideal sorbent platforms for small-molecule sorbates. This approach transformed sorbent design for such separations and has provided several performance benchmarks in trace gas capture-enabled purifications.

Free energy calculations have great potential to accelerate drug discovery projects by predicting relative protein–ligand binding affinities. But how accurate are these predictions and how accurate can they become? A recent report assesses the state of the art in such calculations and compares it to experimental approaches.

Seventy years ago, Stanley L. Miller described the synthesis of amino acids from a simple mixture of gases, spurring investigations into the chemical origins of life. Here we discuss the rise, fall and renaissance of endogenous amino acid production.

Late-stage modification of peptides with photoactivatable groups often weakens their binding interaction with target proteins. Now, this challenge has been addressed using large libraries of cyclic peptides with photocrosslinkers incorporated prior to screening.

The synthesis of MXenes is generally constrained by poorly understood and largely uncontrollable chemical reactions. Now, with the use of chemical scissors and guest intercalants, new MXenes have been created with finely tuned microstructures, compositions and surface ligands.

Informatics approaches play an increasingly important role in accelerating the advances of modern materials science. A recent study reports the development of predictive machine learning models to guide the de novo design of through-space charge transfer polymers with full-colour-tunable emission.

The interactions of lipid bilayer cell membranes with liquid biomolecular condensates are key to many biological processes, including endocytosis. New research shows a model system of liposomes that are able to engulf droplets, effectively mimicking endocytosis.

Twenty five years ago, Christopher Lipinski and colleagues published arguably the most influential sentence in small-molecule drug discovery. Their cleverly crafted ‘rule of 5’ (Ro5) mnemonic was adopted into everyday medicinal chemistry practice and has influenced a generation of small-molecule drug discovery scientists. Five times five years later, we consider the impact of the Ro5 and ask to what extent it should still guide today’s medicinal chemistry efforts.