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 chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

and

chelating agent Chelation is a type of bonding of ions and 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 ligands ar ...

Phenanthroline 1,10-Phenanthroline (phen) is a heterocyclic organic compound. It is a white solid that is soluble in organic solvents. The 1,10 refer 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 agen ...

s ( Doebner-Miller reaction/condensation) of o-nitroaniline ( 2-Nitroaniline) 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. It is isomeric with ''m''-phenylenediamine and ''p''-phenylenediamine. Preparation ...

, 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 refer 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 In chemistry, 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 t ...

complexes. The copper-catalyzed release of NO⁺ ( nitrosonium) 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'' denot ...

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 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 (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

in adult

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

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 heart. ...

. Those expressing eGFP also have been observed to lose eGFP

fluorescence Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...

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 perturbed 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