Met over-oxidation to sulfone

Further oxidation of Met sulfoxide gives Met sulfone — irreversible. +32 Da.

Why it happens (mechanism)

Strong oxidants (HClO₄, performic acid, H₂O₂ at high concentration) push Met(O) → Met(O₂). The S now has +VI oxidation state; not reducible by mild reductants.

When it strikes (triggers)

Performic acid (used in disulfide oxidation), H₂O₂ excess, hot acid + air for prolonged time.

How to spot it (MS signature)

+31.99 Da. Same mass as 2× oxidation (e.g., Met sulfoxide + a separate oxidation elsewhere) — locate by MS/MS.

How to prevent it

• Strictly avoid performic acid for Met-containing peptides.
• Limit H₂O₂ in disulfide-formation protocols; use DMSO or air instead.

If it already happened (salvage)

• Not reducible by common reagents. Considered permanent damage.

Source

Yi Yang, Side Reactions in Peptide Synthesis (Elsevier, 2016), Chapter 9, §9.2.