Neocuproine is a

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

and

chelating agent Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

Phenanthroline 1,10-Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. The 1,10 refers to the location of the nitrogen atoms that replace CH's in the hydrocarbon called phenanthrene. Abbreviated " ...

ligands were first published in the late 19th century, and the derivatives substituted at the 2 and 9 positions are among the most studied of the modified phenanthrolines.

Synthesis and structure

Neocuproine can be prepared by sequential

Skraup reaction The Skraup synthesis is a chemical reaction used to synthesize quinolines. It is named after the Czech chemist Zdenko Hans Skraup (1850–1910). In the archetypal Skraup reaction, aniline is heated with sulfuric acid, glycerol, and an oxidizing a ...

s ( Doebner-Miller reaction/condensation) of o-nitroaniline (

2-Nitroaniline 2-Nitroaniline is an organic compound with the formula H2NC6H4NO2. It is a derivative of aniline, carrying a nitro functional group in position 2. It is mainly used as a precursor to o-phenylenediamine. Synthesis 2-Nitroaniline is prepared commer ...

) with crotonaldehyde diacetate. An alternate synthesis involves the condensation of

o-phenylenediamine ''o''-Phenylenediamine (OPD) is an organic compound with the formula C6H4(NH2)2. This aromatic diamine is an important precursor to many heterocyclic compounds. OPD is a white compound although samples appear darker owing to oxidation by air. I ...

, m-nitrobenzenesulphonate, and crotonaldehyde diacetate. This method gives higher yields but is less economical. Neocuproine crystallizes as a

dihydrate In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was understo ...

and a hemihydrate. NIPHOJ

Coordination chemistry

In the early 1930s,

phenanthroline 1,10-Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. The 1,10 refers to the location of the nitrogen atoms that replace CH's in the hydrocarbon called phenanthrene. Abbreviated " ...

derivatives became known for their use as colorimetric indicators for many transition metals. Neocuproine proved to be highly selective for copper(I). The resulting complex, u(neocuproine)₂sup>+ has a deep orange-red color. The properties of copper(I) neocuproine complexes have been widely studied, e.g. for the preparation of

catenane In macromolecular chemistry, a catenane () is a mechanically interlocked molecular architecture consisting of two or more interlocked macrocycles, i.e. a molecule containing two or more intertwined rings. The interlocked rings cannot be se ...

and

rotaxane A rotaxane () is a mechanically interlocked molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a macrocycle (see graphical representation). The two components of a rotaxane are kinetically trapped since ...

complexes. The copper-catalyzed release of NO⁺ (

nitrosonium The nitrosonium ion is , in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. It can be viewed as nitric oxide with one electron removed. This ion is usually o ...

) from

S-Nitrosothiol In organic chemistry, ''S''-nitrosothiols, also known as thionitrites, are organic compounds or functional groups containing a nitroso group attached to the sulfur atom of a thiol. ''S''-Nitrosothiols have the general formula , where ''R'' deno ...

s is inhibited by neocuproine. Relative to 1,10-

, neocuproine bears steric bulk flanking the nitrogen donor sites. A major consequence is that complexes of the type (neocuproine)₃sup>n+ are disfavored, in contrast to the situation with phenanthroline ligands that lack substitution in the 2,9 positions. The ligand

bathocuproine Bathocuproine is an organic compound with the formula . It is related to 1,10-phenanthroline by the placement of two methyl groups and two phenyl groups in the 2,9 and 4,7 positions, respectively. Like 1,10-phenanthroline, bathocuproine is a bid ...

is similar to neocuproine, but has phenyl substituents at the 4,7-positions.

Other metals

Platinum forms the square planar complexes tX₂(2,9-dimethyl-1,10-phenanthroline) Neocuproine has also been discovered to have properties that cause fragmentation and disappearance of the

melanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...

in adult

zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...

. Those expressing eGFP also have been observed to lose eGFP

fluorescence Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colore ...

in the presence of neocuproine.O’Reilly-Pol, Thomas; Johnson, Stephen L. "Neocuproine Ablates Melanocytes in Adult Zebrafish" ''Zebrafish'' 5(4). Mary Ann Liebert, Inc. 2008.

References

Appendix: NMR Shifts

The following figures contain information on the

nuclear magnetic resonance Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...

spectroscopic data of neocuproine (from Chandler et al.): {, class="wikitable" , +¹H Decoupled ¹³C NMR , - , Substituent , Chemical Shift (δ ppm) , - , C-2 , 159.2 , - , C-10b , 145.1 , - , C-4 , 136.2 , - , C-4a , 126.7 Phenanthrolines