biostudies-literatureLin LDivision of ChemistryAmerican Chemical Society Petroleum Research FundRutgers, The State University of New Jersey34395-34410https://www.ebi.ac.uk/biostudies/studies/S-EPMC12464984biostudies-literatureUnknown147(38)Carbon-hydrogen bond activation is a pillar of synthetic chemistry. While it is generally accepted that Pd is more facile than Ni in C-H activation catalysis, there are no experimental platforms available to directly compare the magnitude of C-H bond weakening between Ni and Pd prior to bond scission. This work presents the first direct measurements of C(sp³)-H bond acidity (p<i>K</i>_a) and bond dissociation free energy (BDFE) for a species containing a ligated alkane-palladium interaction (R₂CH₂···Pd), also known as an agostic interaction. Through standard-state equilibrium measurements and advanced computational modeling, we show that Pd acidifies C(sp³)-H bonds 100,000 times more than Ni (5 p<i>K</i>_a units), indicating tJournal of the American Chemical SocietyA 100,000-Fold Increase in C-H Bond Acidity Gives Palladium a Key Advantage in C(sp&lt;sup&gt;3&lt;/sup&gt;)-H Activation Compared to Nickel.PMC1246498466371-ND324429042018753Hansen ALalancette RAProkopchuk DELin LKucheryavy PSchramm TKfalseA 100,000-Fold Increase in C-H Bond Acidity Gives Palladium a Key Advantage in C(sp&lt;sup&gt;3&lt;/sup&gt;)-H Activation Compared to Nickel.Carbon-hydrogen bond activation is a pillar of synthetic chemistry. While it is generally accepted that Pd is more facile than Ni in C-H activation catalysis, there are no experimental platforms available to directly compare the magnitude of C-H bond weakening between Ni and Pd prior to bond scission. This work presents the first direct measurements of C(sp³)-H bond acidity (p<i>K</i>_a) and bond dissociation free energy (BDFE) for a species containing a ligated alkane-palladium interaction (R₂CH₂···Pd), also known as an agostic interaction. Through standard-state equilibrium measurements and advanced computational modeling, we show that Pd acidifies C(sp³)-H bonds 100,000 times more than Ni (5 p<i>K</i>_a units), indicating t2025-01-01T00:00:00Z2025 Sep2026-06-03T21:10:54.461Z2026-05-01T03:11:04.382ZS-EPMC124649844092392710.1021/jacs.5c07649