From interpretive expertise to multimodal analytical inference Summary Determining a molecule’s configuration, or resolving its enantiomers on a column, has traditionally meant comparing experimental data against a computed reference a process gated by quantum chemistry and by expert judgement. Machine learning is now compressing that comparison from hours to seconds and, in chiral chromatography, is …
Why chirality has to be built into a molecular representation before any model can learn it Episode 1 of 5 Summary Two enantiomers can differ by an order of magnitude in potency, yet to most molecular machine learning models they are the same molecule. This is not a data problem that more training examples will …
Episode 1: Teaching Machines Molecular Handedness Read More »
When a Biaryl Bond Became a Drug-Design Advantage—and a Development Challenge Introduction: What if a “rotatable bond” could influence the fate of a drug? I recently came across a fascinating perspective written by scientists directly involved in the development of sotorasib, a KRAS G12C inhibitor exhibiting atropisomerism. Their article, “Addressing Atropisomerism in the Development of …
How chiral methods and isolated standards are justified in a dossier, and a calibrated view of the future The regulatory position on stereochemical purity Regulators have treated stereochemistry as a quality and development issue for decades, and the core position has been stable even as the vocabulary evolved. FDA’s 1992 stereoisomer guidance requires that the …
Episode 5: Defending the Method: Regulatory Expectations and Where the Field Is Heading Read More »
“Turning an analytical separation into an isolated, characterised, defensible impurity standard” Why isolate a chiral impurity at all Analytical scientists ask for isolated chiral impurities when a chromatogram is no longer enough. The reasons are concrete: structural elucidation of an unknown peak, preparation of a reference standard, response-factor determination, qualification under ICH impurity expectations, forced-degradation …
Episode 4: From Peak to Standard: Preparative Isolation of Chiral Impurities Read More »
What modern chiral separation science can do now, and where the honest limits still lie The present technology landscape The most useful framing of the current landscape is that it is no longer sensible to ask, in the abstract, whether chiral HPLC or chiral SFC is “the best” approach. Modern laboratories operate with both, or …
Episode 3: State of the Art: Selectors, SFC, Speed, and Sensible Automation Read More »
From a structural diagnosis of the analyte to a defendable, robust, lifecycle-ready method Start with the molecule, not the column catalogue A credible chiral method does not begin with random column screening. It begins with a short structural diagnosis of the analyte and the likely impurity set. The pKa values indicate whether the analyte is …
Episode 2: Developing a Chiral HPLC Method: A Structure-Led Workflow Read More »
The pharmaceutical meaning of chirality, the real impurity space, and where chiral HPLC fits The pharmaceutical meaning of chirality Chirality matters in drug development for a simple reason. Biological systems are chiral, so the body does not experience two stereoisomers as the same molecule. FDA stated this explicitly in its landmark 1992 stereoisomer guidance, noting …
Episode 1: Why Chirality Still Matters: Stereochemistry as a Critical Quality Attribute Read More »
Introduction Chirality has already transformed how agrochemicals are designed, evaluated, and applied. From the early reliance on racemic formulations to today’s enantiopure products such as metalaxyl-M, the trajectory shows a clear shift toward stereochemistry as a cornerstone of innovation. The future of chiral agrochemistry lies at the intersection of asymmetric synthesis, biocatalysis, computational design, and …
Episode 10: Future Directions in Chiral Agrochemistry Read More »
Introduction The development and use of chiral agrochemicals are not governed by science alone. Policy frameworks, regulatory guidance, and industrial strategy all play decisive roles in shaping how stereochemistry is addressed in crop protection. Over the past three decades, regulators have recognized that enantiomers can differ dramatically in efficacy, toxicity, and environmental fate. This recognition …
Episode 9: Regulatory and Industrial Perspectives on Chiral Agrochemicals Read More »