Reactivity, masking of ligand

Subsequent work has shown that it is more common to have a difference in rates for typical ligand reactions, rather than a qualitative difference in reactivity. This is generally true of precipitation reactions as well as more involved reactions. It is therefore necessary to examine the general features of these reactions in considerably greater detail if we wish to appreciate the basic factors which govern the masking of ligand reactions. 

When the ligand consists of both an aromatic system and reactive portions external to the aromatic system, the most interesting changes in reactivity occur in the latter portion of the molecule. These changes may be divided into two classes masking of reactive groups and activation which results from the polarization arising from coordination. 

This masking of the typical ligand reactivity via coordination is a thread which runs throughout early work on these compounds and allowed the concept of the coordination sphere to be put on a definite basis as a result of chemical tests. 

A common choice of crosslinker for this type of reaction is sulfo-SMCC, which has been used extensively for antibody conjugation (Chapter 20, Section 1.1). A better option for dendrimer conjugation is to use a similar crosslinker design, but one that contains a hydrophilic PEG spacer arm to promote dendrimer hydrophilicity after modification. Derivatization of an amine-dendrimer with a NHS-PEG-maleimide can create an intermediate that is coated with water-soluble PEG spacers. This modification helps to mask any potential for nonspecific interactions that the PAMAM surface may have, while providing terminal thiol-reactive maleimides for coupling ligands (Figure 7.10). 

At the present time the paucity of data renders it impossible to give a complete picture of the various ways in which coordination may affect the reactivity of aromatic ligands. It is possible to indicate the effects which the coordination process may have on the aromatic reactivity, however, to show how masking and polarization may affect reactivities, and to show at least a few instances where coordination may provide useful synthetic routes to some aromatic compounds. 

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