The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the interaction energies between the two distorted molecules. The energy required to distort the molecules is called the activation strain or distortion energy. This energy is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by the stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions.

Optimizing surface passivation: Unproductive charge recombination at surface defects can limit the efficiency of hybrid perovskite solar cells, but these defects can be passivated by the binding of small molecules. Wang et al. studied three such small molecules—theophylline, caffeine, and theobromine—that bear both carbonyl and amino groups. For theophylline, hydrogen bonding of the amino hydrogen to surface iodide optimized the carbonyl interaction with a lead antisite defect and improved the efficiency of a perovskite cell from 21 to 22.6%. Science , this issue p. 1509

The affinities of hosts—ranging from small synthetic cavitands to large proteins—for organic molecules are well documented. The average association constants for the binding of organic molecules by cyclodextrins, synthetic hosts, and albumins in water, as well as of catalytic antibodies or enzymes for substrates are 10^3.5±2.5 M⁻¹. Binding affinities are elevated to 10^8±2 M⁻¹ for the complexation of transition states and biological antigens by antibodies or inhibitors by enzymes, and to 10^16±4 M⁻¹ for transition states with enzymes. The origins of the distributions of association constants observed for the broad range of host–guest systems are explored in this Review, and typical approaches to compute and analyze host–guest binding in solution are discussed. In many classes of complexes a rough correlation is found between the binding affinity and the surface area that is buried upon complexation. Enzymes transcend this effect and achieve transition‐state binding much greater than is expected from the surface areas.

Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry; now the activation and cleavage of these bonds using nickel catalysts is used to convert amides to esters. Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. In this paper the authors demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. They used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. Amides are common functional groups that have been studied for more than a century1. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond1,2. Although amides can readily be cleaved by enzymes such as proteases3, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon–nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon–heteroatom or carbon–carbon bonds using non-precious-metal catalysis.