When the first titanium complex with anticancer activity was identified in the 1970s, it was attractive, based on the presence of the dichloride unit in TiCl 2 Cp 2 (Cp = η-C 5 H 5 ) 2 , to assume its mode of biological action was closely aligned with cisplatin [cis-PtCl 2 (NH 3 ) 2 ]. Over the intervening 40 years however a far more complicated picture has arisen indicating multiple cellular mechanisms of cellular action can be triggered by titanium anti-cancer agents. This tutorial review aims to unpick the historical data and provide new researchers, without an explicit cancer biology background, a contemporary interpretation of both older and newer literature and to review the best techniques for attaining the identities of the biologically active titanium species and how these interact with the cancer cellular machinery. Key learning points(1) Understanding the problems in defining 'modes of action' in order to effectively design small molecular titanium-based therapeutic, agents when moving beyond simple 'structure vs. activity' correlations. (2) The dangers of over generalisation in historical 'mode of action' proposals in the absence of rigorous control experiments leading to proposals not fully in line with all (especially later) observations. (3) Titanium induced cellular morphology changes and contemporary thoughts on mode(s) of actionpresented in a way chemical scientists can 'get to grips with them' -understanding the hall marks of cellular death modes induced by titanium anti-cancer agents. (4) Modern tools for probing Ti-drug mechanisms of action, including: chiral probe complexes, added external proteins (transferrin, serum albumin); titanium solution speciation, and an overview of contemporary chemical-biology techniques of relevance to discovery of 'modes/mechanisms of action'.

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Understanding of the 1,4-addition of organocuprates, especially LiCuR 2 species, to enone Michael acceptors has blossomed in the light of recent kinetic, NMR, and theoretical investigations. These investigations have been reviewed and are compared to the various reaction coordinates they support. Emphasis is placed on relating the theoretical calculations to physical data extracted from real systems. The mechanism of cuprate conjugate addition is compared to related reactions including: additions to ynones, alkene carbocupration, and S N 2A allylic and propargylic substitution reactions. Scheme 1 Cuprate mediated 1,4-addition of 'MR' to a,b-unsaturated systems (enones). R and Y represent generic groups. The 'E + ' source may be H + , RI, RCHO, etc.

Weigh it out in air! The DABAL reagent (Me3Al)2⋅(DABCO) (DABCO=1,4‐diazabicyclo[2.2.2]octane) can be easily handled under normal laboratory conditions. Furthermore, chiral secondary alcohols can be efficiently prepared from prochiral aldehydes (see scheme; TOF=turnover frequency) by using either DABAL or AlR3 reagents (R=Me, Et). Thus, DABAL can be used as an efficient, convenient alternative to the Schumann–Blum reagent.

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