We tested the general applicability of in situ proteolysis to form protein crystals suitable for structure determination by adding a protease (chymotrypsin or trypsin) digestion step to crystallization trials of 55 bacterial and 14 human proteins that had proven recalcitrant to our best efforts at crystallization or structure determination. This is a work in progress; so far we determined structures of 9 bacterial proteins and the human aminoimidazole ribonucleotide synthetase (AIRS) domain.

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The formation of C-C bonds directly from catalytic reductive cross-coupling of two different electrophiles represents one of the practical synthetic protocols that differs from the conventional nucleophile/electrophile coupling methods. Particularly the reductive coupling of alkyl electrophiles with other electrophiles is still a challenge. This account summarizes the advances of the formation of C(sp 3 )-C(sp 3 ) bonds between two alkyl electrophiles, with emphasis on the control of chemoselectivity that is exceedingly challenging to achieve due to similar structures and reactivities of two unactivated alkyl halides. The coupling of alkyl halides with aryl or acyl electrophiles was also discussed based on the chemistry developed by our group, followed by a brief overview for the reactions of tertiary alkyl halides. In the end, a brief outlook of the challenges in this exciting field was illustrated. Whereas the reaction mechanisms generating alkylalkyl products are proposed to involve reactions of Ni(I) species with alkyl halides to generate Ralkyl-Ni(III)-Ralkyl intermediates through a radical/Ni cage-rebound process, evidence seemingly supports that a radical chain mechanism governs the acylation and arylation of alkyl halides. The latter features a cage-escaped alkyl radical.