Ion triggered alkylation of biological targets by silyloxy aromatic agents

A silyloxy aromatic probe having the formula:

• ##STR31## wherein R.sub.2 =--OSiR.sub.6 R.sub.7 R.sub.8, R.sub.3 =--CR.sub.9 R.sub.10 X R.sub.1,R.sub.4 and R.sub.5 =hydrogen;
• said R.sub.6, R.sub.7, R.sub.8 =alkyl or aromatic groups;
• said R.sub.9 and R.sub.10 is an aliphatic or alkyl group, X =leaving group;
• L is a linking group for attachment to a probe which may be positioned at any carbon atom of the ring;
• and Pr is a probe for binding to DNA or RNA.

A process for alkylating DNA or RNA, comprising steps of:

• a) providing a probe for binding to DNA or RNA;
• b) providing a silyloxy benzene derivative for linking to the probe;
• c) linking the probe to the silyloxy benzene derivative to form a targeted alkylating agent;
• d) introducing the targeted alkylating agent to an in vitro system containing DNA or RNA, whereby the probe associates with the DNA or RNA, localizing the linked silyloxy aromatic derivative near the DNA or RNA;
• and
• e) activating the targeted alkylating agent, thereby causing covalent binding between the linked aromatic derivative and the DNA or RNA proximal to the association site of the probe with the DNA or RNA.

A process as recited in claim wherein the targeted alkylating agent has the molecular formula:

• ##STR32## wherein one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is --OSiR.sub.6 R.sub.7 R.sub.8 ;
• wherein
• when R.sub.1 =--OSiR.sub.6 R.sub.7 R.sub.8, then R.sub.2 and/or R.sub.4 is =--CR.sub.9 R.sub.10 X;
• when R.sub.2 =--OSiR.sub.6 R.sub.7 R.sub.8, then R.sub.1, R.sub.3 and/or R.sub.5 is =--CR.sub.9 R.sub.10 X;
• when R.sub.3 =--OSiR.sub.6 R.sub.7 R.sub.8, then R.sub.2 and/or R.sub.4 is =--CR.sub.9 R.sub.10 X;
• when R.sub.4 =--OSiR.sub.6 R.sub.7 R.sub.8, then R.sub.1, R.sub.3 and/or R.sub.5 is =--CR.sub.9 R.sub.10 X;
• when R.sub.5 =--OSiR.sub.6 R.sub.7 R.sub.8, then R.sub.2 and/or R.sub.4 is =--CR.sub.9 R.sub.10 X;
• wherein any remaining R.sub.1 -R.sub.5 substituents that are not --OSiR.sub.6 R.sub.7 R.sub.8 or --CR.sub.9 R.sub.10 X are hydrogen atoms;
• wherein said R.sub.6, R.sub.7, R.sub.8 =alkyl or aromatic groups;
• said R.sub.9 and R.sub.10 is an aliphatic or alkyl group;
• X=leaving group;
• L is a linking group for attachment to a probe which may be positioned at any carbon atom of the ring;
• and Pr is a probe for binding to DNA or RNA.

A silyloxy aromatic compound, comprising a substituted benzene ring, wherein a position on the benzene ring is occupied by an --OSiR.sub.6 R.sub.7 R.sub.8 group and at least one position on the benzene ring in conjugation with the --OSiR.sub.6 R.sub.7 R.sub.8 group is occupied by a --CR.sub.9 R.sub.10 X group, in which

• R.sub.6, R.sub.7, and R.sub.8 are selected from the group consisting of alkyl and aromatic groups;
• R.sub.9 and R.sub.10 are selected from the group consisting of alkyl and aromatic groups;
• and
• X is a leaving group.