The alpha effect refers to the increased nucleophilicity of an atom due to the presence of an adjacent (alpha) atom with lone pair electrons. This first atom does not necessarily exhibit increased basicity compared with a similar atom without an adjacent electron donating atom. The effect is well established with many theories to explain the effect but without a clear winner.
The effect was first observed by Jencks and Carriuolo in 1960 in a series of chemical kinetics experiments involving the reaction of the ester p-nitrophenyl acetate with a range of nucleophiles. Regular nucleophiles such as the fluoride anion, aniline, pyridine, ethylene diamine and the phenolate ion were found to have pseudo first order reaction rates corresponding to their basicity as measured by their pKa. Other nucleophiles however reacted much faster than expected based on this criterion alone. These include hydrazine, hydroxylamine, the hypochlorite ion and the hydroperoxide anion.
In 1962 Edwards and Pearson (the latter of HSAB theory) introduced the phrase alpha effect for this anomaly. He offered the suggestion that the effect was caused by a transition state (TS) stabilization effect: on entering the TS the free electron pair on the nucleophile moves away from the nucleus causing a partial positive charge which can be stabilized by an adjacent lone pair as for instance happens in any carbocation.
Over the years many additional theories have been put forward attempting to explain the effect. A ground state stabilizing effect assumes that the alpha lone-pair and nucleophilic electron pair destabilize each other by electronic repulsion thereby increasing the ground state and making it more reactive. Stabilization of the transition state is possible by assuming some TS free radical character or assuming that the TS has more advanced nucleophile-substrate bond formation. The polarizability of the nucleophile or involvement of intramolecular catalysis also plays a role. One recent in silico contribution did find a correlation between the alpha effect and the so-called deformation energy which is the electronic energy required to bring the two reactants together in the transition state.
The alpha effect is also dependent on solvent but not in a predictable way: it can increase or decrease with solvent mix composition or even go through a maximum.