Nanotechnology-Enabled Sensors

376 Chapter 7: Organic Nanotechnology Enabled Sensors
to facilitate the covalent coupling. Some activation strategies for forming
amides will be outlined below.
Example 1: Amide bond formation using carbodiimide
Often in synthetic organic chemistry, compounds containing the carbodiimide
functional groups are utilized to activate carboxylic acids for the
formation of amides or esters. A carbodiimide is a functional group which
contains –N=C=N–.
Forming such a bond usually involves two steps: in the first step, the
carboxylic acid is activated by the carbodiimide reagent to form an Oacylisourea
intermediate. This is followed by a nucleophilic displacement
of the intermediate by the amine to form the final amide bond.
Several side reactions can be produced in the formation of an amide
using a carbodiimide. 5 The carbodiimide may react with the acid to
produce: the O-acylisourea, which can is a carboxylic ester and amide and
urea. The O-acylisourea can react with carboxylic acid to give a carboxylic
anhydride. This carboxylic anhydride may continue the reaction further to
produce the stable N-acylurea and the desired amide.
Example 2: Amide bond formation using the displacement of esters
Amide bonds can also be formed by making active ester molecules from
carboxylic acids, and then displacing them with amines. An ester (Fig. 7.5)
in an organic compound in which an organic group (symbolized by R')
replaces the hydrogen atom in a carboxylic group.
Fig. 7.5 An ester.
R
O
O R'
If heated, esters can react with primary or secondary amines to produce
amides. However, in many cases (such as protein immobilization) we
cannot apply heat because the organic components can be damaged. Esters
can be formed in NH2- -carboxyl covalent interaction. The -NH2 amino
coupling method (self-assembled monolayer sample with -NH2) can be
used as shown in Fig. 7.6.