phi-sensitivity is the change in ignition delay time (IDT) with respect to the fuel-to-air equivalence ra tio (phi). High phi-sensitivity is a desirable fuel property for applications in advanced compression ignition and multi-mode engine designs. Understanding how phi-sensitivity depends on chemical structure is essential for selecting promising biofuels from the ever-growing list of proposed candidates. In this study, we investigate the effect of chemical structure on phi-sensitivity with experiment, simulation, and theory. Experimental Advanced Fuel Ignition Delay Analyzer (AFIDA) measurements for 2,4-dimethylpentane and diisopropyl ether provide evidence that branching and functional groups strongly impact phi-sensitivity. Further insights into this dependence are obtained with phi-D kinetic simulations with existing mechanisms for n-pentane, diethyl ether, 3-pentanone, n-heptane, 2-methylhexane, 2,4-dimethylpentane, and 2,2,3-trimethylbutane. Quantum mechanical (QM) G4 calculations of low-temperature reactions help explain the observed experimental and simulation trends. Specifically, these QM calculations provide theoretical estimates of the ketohydroperoxide (KHP) dissociation rates, the HO2 formation rates from peroxy radical (ROO), and the "cross-over" temperatures, i.e., the temperature at which ROO dissociation is favored compared to hydroperoxyl radical (QOOH) formation. Each of these reaction rates is compared to the n-alkane reference point to determine the impact of branching and different functional groups. Although kinetic mechanisms typically assume that KHP dissociation rates are invariant of chemical environment, our QM results suggest that this rate can span a range of roughly two orders of magnitude. We also discuss the importance of including the peroxy-hydroperoxy (OO-OOH) hydrogen transfer reaction for branched ethers. Finally, the insights gained assist in proposing a highly phi-sensitive compound, namely, isopropyl propyl ether. (C) 2020 The Combustion Institute. Published by Elsevier Inc. All rights reserved.