Table 3.

Calculated Nucleophilic Indices (ω^-) for Type-2 Alkene Reactions With Possible Nucleophilic Targets

Electrophilea	ω- Cys (−1)	ω- Cys (0)	ω- His (0)	ω- Lys (+1)
NEM	2.51	0.194	0.250	0.277
Acrolein	2.03	0.103	0.123	0.253
HNE	1.93	0.083	0.102	0.287
MVK	1.83	0.064	0.081	0.319
MA	1.59	0.069	0.063	0.332
ACR	1.50	0.036	0.048	0.346

The nucleophilicity index (ω^-) was calculated as ω^- = η_A (μ_A - μ_B)²/2(η_A - η_B)², where η = (E_LUMO-E_HOMO)/2, μ = (E_LUMO+E_HOMO)/2, A = reacting nucleophile and B = reacting electrophile (see 42 for details). For each nucleophile, the respective ionization-state is presented in parentheses. The nucleophilicity index is a higher order parameter that considers the respective hardness and chemical potential of the electrophilic (type-2 alkene) and nucleophilic (cysteine, histidine or lysine) reactants and is, therefore, a measure of the likelihood of subsequent adduct formation. As suggested by the respective ω-values, the type-2 alkenes preferentially form adducts with cysteine thiolate sites as opposed to histidine, lysine or thiol residues. Abbreviations: NEM = N-ethylmaleimide, HNE = 4-hydroxy-2-nonenal, MVK = methyl vinyl ketone, MA = methyl acrylate and ACR = acrylamide.