Temperature-induced spectral anomalies in doxorubicin-A Raman study

Doxorubicin (DOX) is a widely used chemotherapeutic agent whose spectroscopic behavior can provide insight into its structural dynamics and interactions. Here, we investigate temperature-induced changes in the Raman spectra of DOX between 100 and 300 K, combining experimental measurements with density functional theory (DFT)-based simulations. Temperature-dependent Raman scattering experiments, performed under controlled cryogenic and ambient conditions, revealed pronounced spectral intensity variations accompanied by changes in the luminescence background. Detailed analysis and comparison with simulated resonance Raman spectra showed that these changes originate primarily from temperature-dependent resonance effects. Using the R2SCAN/def2-TZVP level of theory with D3 dispersion corrections, the most stable conformers of DOX, DOX-HCl, and DOX-H⁺ were identified, and their resonance Raman spectra were computed. Quantitative comparison using the SARA algorithm yielded 91%-94% agreement between theory and experiment across all temperatures. Increasing temperature is accompanied by a redistribution of relative Raman intensities, with reduced contributions from bands assigned to motions involving hydrogen-bonds and enhanced contributions from ring-dominated modes. This trend is discussed in the context of temperature-dependent resonance conditions.