Green chemistry metrics such as process mass intensity, PMI, and the complete environmental factor, cEF, are well-established yardsticks for gauging the sustainability of a chemical process, yet their routine use in peptide synthesis remains the exception rather than the rule. The reason is structural: both solid-phase peptide synthesis, SPPS, and liquid-phase peptide synthesis, LPPS, involve tens of iterative coupling and deprotection cycles, each demanding careful accounting of resin mass, reagent equivalents, and solvent volumes before a single PMI value emerges. Existing general-purpose tools such as the ACS Green Chemistry Institute Pharmaceutical Roundtable PMI calculator were designed for small-molecule workflows and do not map cleanly onto repetitive peptide assembly steps or the resin-handling operations unique to SPPS. The result is a well-documented gap: researchers acknowledge PMI as a valuable metric but defer the calculation until it becomes a retrospective chore, if it happens at all.
Researchers in the Albericio and De La Torre Lab at the University of KwaZulu-Natal, published in Org. Process Res. Dev., address this gap with a peptide-specific Excel-based tool that automates PMI and cEF calculation from parameters chemists already record during synthesis. The tool organizes data entry into five structured sections covering resin or soluble-tag details, amino acid inputs, coupling reagents and deprotection cocktails, solvent consumption at each stage, and a final auto-calculated output. Drop-down menus handle common resin types, coupling reagents, and solvents, while built-in formulas convert raw experimental entries directly into mass-based sustainability metrics. Critically, the tool covers both SPPS and LPPS workflows on a single platform, enabling direct comparison of the two strategies under identical accounting rules. The authors validated the approach by recalculating PMI values for previously published syntheses, confirming that the Excel tool reproduces manually derived values while reducing calculation time to approximately 40 minutes per synthesis.
By converting a labor-intensive retrospective exercise into a routine step that fits within experimental planning, the tool positions quantitative sustainability assessment as a proactive design parameter rather than an afterthought. The ability to compare SPPS against LPPS workflows quantitatively, and to account for solvent recycling through a PMI-with-recycling formulation, gives both academic and industrial groups a common language for sustainability reporting. The full protocol and downloadable Excel tool are available in the Supporting Information of the original publication.
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