Log out Go to App
Go to App

Learning Materials

Features

Discover

Chapter 6: Problem 7

Amino-seco-CBI-TMI (3) is a minor groove alkylating agent. Show a mechanism for alkylation of DNA that does not involve direct \(\mathrm{S}_{\mathrm{N}} 2\) displacement of the chloride by DNA.

Short Answer

Expert verified
The mechanism of DNA alkylation does not involve direct SN2 displacement of the chloride. Instead, it involves the generation of a reactive amine anion that then undergoes a nucleophilic attack to form a three-membered ring. The ring opens, expelling a chloride ion and forming a carbocation that reacts with the nitrogen nucleophiles in DNA, causing the alkylation.

Step by step solution

01

Generate Reactive Intermediate

Initially, Amino-seco-CBI-TMI (3) reacts with a base (for example, the amine group on a nucleotide in DNA) to deprotonate and generate a reactive amine anion. This is generally referred to as the removal of a proton or a process of deprotonation. You can denote the reactive amine anion by showing a negative charge on the oxygen atom.
02

Nucleophilic Attack

In the second step, the generated amine anion acts as a nucleophile and attacks the positively polarized carbon bonded to the chloride. The polar nature of this carbon-chlorine bond makes it susceptible to nucleophilic attack. This reaction step would lead to the formation of a three-membered ring structure, with the negatively charged amine anion forming a bond with the positively polarized carbon atom.
03

Ring Opening

To relief the strain of the three-membered ring, there is a breakage happens between the carbon-chlorine bond which leads to chloride ion expulsion, the subsequent generation of a highly reactive carbon-based intermediate (a carbocation). In this step, focus on representing the electron movement from the carbon-chlorine bond and the resultant carbocation.
04

Reaction with DNA

Finally, this carbocation intermediate reacts with the DNA – specifically with the nitrogen nucleophiles on DNA bases (for instance, guanine). This interaction forms a covalent bond between the alkylating agent and DNA, ultimately completing the alkylation process. It is essential to show the carbocation formation of a covalent bond with the DNA's nitrogen atom.

Unlock Step-by-Step Solutions & Ace Your Exams!

  • Full Textbook Solutions

    Get detailed explanations and key concepts

  • Unlimited Al creation

    Al flashcards, explanations, exams and more...

  • Ads-free access

    To over 500 millions flashcards

  • Money-back guarantee

    We refund you if you fail your exam.

Start your free trial

Over 30 million students worldwide already upgrade their learning with Vaia!

One App. One Place for Learning.

All the tools & learning materials you need for study success - in one app.

Get started for free

Most popular questions from this chapter

What properties would you incorporate into the design of DNA intercalating agents?

Draw a mechanism for the topoisomerase-catalyzed cleavage of DNA that gives the free \(5^{\prime}\)-end.

Alkylating agents are used in cancer chemotherapy to interfere with DNA biosynthesis or replication. Why can these be useful considering that normal cells also need DNA?

It was proposed that a common mechanism for antibiotics might be hydroxyl radical oxidation of guanine to 7,8 -dihydro-8-oxoguanine (7), which is enzymatically excised from DNA and replaced by guanine; however, when too many guanines are oxidized, DNA strand breakage occurs, killing the cell. Draw a mechanism for how guanine could be oxidized by hydroxyl radicals to 7 .

\(N, N\)-Diethylnitrosoamine (4) is carcinogenic, resulting in ethylation of DNA. Two other products formed are acetaldehyde and \(\mathrm{N}_{2}\). Under anaerobic conditions or in the absence of NADPH no carcinogenicity is observed. Draw a mechanism for DNA ethylation by this compound.
See all solutions

Recommended explanations on Chemistry Textbooks

Chemical Reactions

Read Explanation

Ionic and Molecular Compounds

Read Explanation

Organic Chemistry

Read Explanation

Chemistry Branches

Read Explanation

Nuclear Chemistry

Read Explanation

Chemical Analysis

Read Explanation
View all explanations

What do you think about this solution?

We value your feedback to improve our textbook solutions.

Study anywhere. Anytime. Across all devices.

Sign-up for free