Phenanthroline

Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. It is used as a ligand in coordination chemistry, forming strong complexes with most metal ions. It is often sold as the monohydrate.
Synthesis.
Phenanthroline may be prepared by two successive Skraup reactions of glycerol with "o"-phenylenediamine, catalyzed by sulfuric acid, and an oxidizing agent, traditionally aqueous arsenic acid or nitrobenzene. Dehydration of glycerol gives acrolein which condenses with the amine followed by a cyclization.
Coordination chemistry.
In terms of its coordination properties, phenanthroline is similar to 2,2'-bipyridine (bipy) but binds metals more tightly since the chelating nitrogen donors are preorganized. Phenanthroline is however a weaker donor than bipy.
Many homoleptic complexes are known. Particularly well studied is [Fe(phen)3]2+, called "ferroin." It was used for the photometric determination of Fe(II). It is used as a redox indicator with standard potential +1.06 V. The reduced ferrous form has a deep red colour and the oxidised form is light-blue. The pink complex [Ni(phen)3]2+ has been resolved into its Δ and Λ isomers. Copper(I) forms [Cu(phen)2]+, which is luminescent.
Bioinorganic chemistry.
The ferroin analogue [Ru(phen)3]2+ has long been known to be bioactive.
1,10-Phenanthroline is an inhibitor of metallopeptidases, with one of the first observed instances reported in carboxypeptidase A. Inhibition of the enzyme occurs by removal and chelation of the metal ion required for catalytic activity, leaving an inactive apoenzyme. 1,10-Phenanthroline targets mainly zinc metallopeptidases, with a much lower affinity for calcium.
Related phen ligands.
A variety of substituted derivatives of phen have been examined as ligands. Substituents at the 2,9 positions confer protection for the attached metal, inhibiting the binding of multiple equivalents of the phenanthroline. Phen itself form complexes of the type [M(phen)3]Cl2 when treated with metal dihalides (M = Fe, Co, Ni). By contrast, neocuproine and bathocuproine form 1:1 complexes such as [Ni(neo/batho-cuproine)Cl2]2.
As an indicator for alkyllithium reagents.
Alkyllithium reagents form deeply colored derivatives with phenanthroline. The alkyllithium content of solutions can be determined by treatment of such reagents with small amounts of phenanthroline (ca. 1 mg) followed by titration with alcohols to a colourless endpoint. Grignard reagents may be similarly titrated.