The Digital Chiroscope: Unlocking Blueprints from Chiroptical Spectroscopy’s Black Box

Quantum mechanical calculations are widely used to interpret experimental data in chemical and biochemical research, supported by user-friendly software and powerful computing resources. Their broad adoption, including by nonexperts, can lead to overinterpretation when calculations fail to achieve the required structural resolution. Chiroptical spectroscopy is a classic example: the absolute configuration (AC) assignment protocol relies entirely on density functional theory (DFT) calculations, so the reliability of the prediction is directly affected by the computational accuracy. We present a dendrogram-based spectral analysis that quantifies the structural resolution of spectroscopic techniques by identifying trends in spectra computed for conformers of the studied compound. Intuitive, visually interpretable, and requiring no specialized expertise, this AI-based approach complements the standard chiroptical protocol as a diagnostic tool, flagging potentially uncertain AC assignments and indicating when validation using additional techniques is warranted. We demonstrate the method with Vibrational (VCD) and Electronic (ECD) Circular Dichroism spectra of several chiral compounds. The analysis transforms the standard chiroptical protocol from the traditional "yes/no/maybe" comparison into a high-resolution "digital chiroscope". For the Salen-PN compound, the analysis reveals numerous conformer pairs exhibiting conformational enantiomorphism, leading to axial chirality dominating the VCD and ECD signatures over point chirality. As a result, conformers with the same AC display almost opposite spectra, challenging a core assumption of the chiroptical protocol and underscoring the importance of our structural-resolution diagnostic.