Greenness, blueness, and whiteness evaluation of a density functional theory-validated photoinduced electron transfer deactivation protocol for sensitive fluorescence determination of butenafine

Abstract

In this study, we introduce a photoinduced electron transfer (PET)-off fluorescence enhancement strategy for the sensitive detection of butenafine hydrochloride (BFH), an antifungal agent exhibiting inherently low fluorescence due to PET effects. Protonation of BFH’s tertiary amine moiety effectively suppressed the PET pathway, resulting in a remarkable fluorescence enhancement. Density Functional Theory (DFT) calculations validated this mechanism, revealing distinct shifts in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies between protonated and unprotonated BFH states. The developed method demonstrated exceptional analytical performance, achieving a linear detection range of 15.0–150.0 ng/mL and a detection limit of 2.5 ng/mL. Its practical utility was confirmed through the successful quantification of BFH in a commercial antifungal cream, with recoveries of 98.2–101.8 %. Furthermore, the environmental sustainability, applicability, and practicality of this PET-off approach were rigorously evaluated using the Analytical GREEnness (AGREE) metric, Blue Applicability Grade Index (BAGI) tool, and Red-Green-Blue (RGB) whiteness algorithm. These assessments highlighted its alignment with green analytical chemistry principles while maintaining robust performance for routine pharmaceutical quality control. Compared to previously reported chromatographic and electrochemical methods, the developed spectrofluorimetric method offers a rapid, cost-effective, and highly sensitive alternative for BFH determination. The method eliminates the need for expensive derivatization agents, labor-intensive sample preparation, and sophisticated instrumentation, making it an eco-friendly and sustainable method appropriate for routine pharmaceutical quality control. Moreover, this work not only advances fluorescence-based sensing strategies but also establishes a framework for integrating computational validation and multi-criteria sustainability analysis into analytical method development.