Figure illustrates this idea in a study of the solvent effects on the pKa of a C(sp 3 )-H bond. The dielectric constants of a typical ionic liquid (IL) and DMSO differ significantly, and these solvents are readily miscible. If the IL and DMSO behaved additively, one would expect a linear relationship between the pKa of the compound and the ratio of IL to DMSO; specifically, a higher percentage of IL should correlate with a higher pKa. This is indeed observed at moderate and high percentages of IL. However, at low percentages of IL, the opposite trend occurs. The paradox is resolved by a synergistic effect between IL and DMSO. At moderate and high concentrations of IL, IL exists as tightly bound neutral ion pairs. At lower concentrations, however, IL exists as dissociated ions, solvated by DMSO. The dissociated ions stabilize the conjugate base, thereby increasing acidity. This example highlights the importance of considering synergistic effects where IL and DMSO interact in a non-purely additive manner, demonstrating mutual interactions. Additionally, synergistic effects manifest in multi-catalyst reaction optimization campaigns. A traditional approach is optimizing each component individually then combining the bestperforming catalysts from the individual optimization studies. However, this approach does not always lead to the best overall performance if there is a negative synergy between different components of catalysts. These interactions can detract from the efficacy expected from the optimal performance of each catalyst in isolation, highlighting the need for holistic optimization approaches that consider the interplay between catalysts to truly enhance the desired reaction. Origin 6. Dichotomy Blurred. The perceived paradox in some cases arises from our longstanding expectation of a clear division between two classes of bonding or mechanistic scenarios. However, this division may not be as pronounced as we assume.