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The origin of the DNA alkylation selectivity was evaluated through analysis of the reversed and sandwiched analogs of duocarmycin SA. Studies suggested that the ground state destabilization of the substrate disrupted the amide stabilization of the alkylation subunit and increased its reactivity toward nucleophiles. The DNA adenine-thymine minor grove binding mediates the reaction.

The adenine N3 alkylation is mediated by additional characteristics that resemble the imposed stereoelectronic control. Reactive 2,3,10,10a-tetrahydrocyclopropa(d)benzo(f)quinol-5-one (CBQ)-based agents alkylate same sites as the corresponding DSA-, CPI-, DA-, and CI-based agents. These agents have less selectivity among the established alkylation sites and low efficiency to alkylate DNA. Adducts obtained from adenine N3 addition to the least substituted cyclopropane carbon were detected under the relevant conditions of limiting agent.

A new synthesis method is proposed for CC-1065 and duocarmycin analogs that incorporate the 2,3,10, 10a-tetrahydro-1H-cyclopropa(d)benzo(f)quinol-5-one (CBQ) alkylation subunit. The synthesis involves a key 6-exo-trig aryl radical alkene cyclization and subsequent Winstein Ar-3' alkylation. These CBQ-based analogs show marked solvolysis reactivity and mixed solvolysis regioselectivity. These analogs are highly stable and their potent activity is correlated with their chemical stability.

Self-assembled helices are used as templates to form helical pores in organic matrices. The imprints are obtained with a high resolution and facilitated by the choice of a high cross-linking density network, which prevents any shrinking of the matrix.

A five-membered ring, associated with the alkylation subunits of CC-1065 and duocarmycin, exhibits geometrical constraints that induce stereoelectronic control on the cleavage of cyclopropane that needs addition to the carbon with least substitution. Chemical and structural properties of N-BOC-CBQ and N-BOC-CB1 reveal the direct relationship of chemical stability to cytotoxic potency.

Identifies subtle structural features that contribute to the regioselectivity of the adenine N3 alkylation reaction. Details of some DNA alkylation properties; Analyses on the adenine N3 adduct obtained by thermal depurination; Benefit of the regiochemcial course of the adenine N3 DNA alkylation reaction; Features that complement regioselectivity.