# Neocuproine

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Neocuproine
> Markdown URL: https://mediated.wiki/source/Neocuproine.md
> Source: https://en.wikipedia.org/wiki/Neocuproine
> Source revision: 1323928326
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

**Neocuproine** is a [heterocyclic](/source/Heterocyclic) [organic compound](/source/Organic_compound) and [chelating agent](/source/Chelating_agent). [Phenanthroline](/source/Phenanthroline) 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.[1][2]

## Synthesis and structure

Neocuproine can be prepared by sequential [Skraup reactions](/source/Skraup_reaction) ([Doebner-Miller reaction](/source/Doebner-Miller_reaction)/condensation) of o-nitroaniline ([2-Nitroaniline](/source/2-Nitroaniline)) with crotonaldehyde diacetate. An alternate synthesis involves the condensation of [o-phenylenediamine](/source/O-phenylenediamine), m-nitrobenzenesulphonate, and crotonaldehyde diacetate. This method gives higher yields but is less economical.[3] Neocuproine crystallizes as a [dihydrate](/source/Dihydrate) and a hemihydrate.

## Coordination chemistry

In the early 1930s, [phenanthroline](/source/Phenanthroline) 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, [Cu(neocuproine)2]+ has a deep orange-red color.[3] The properties of copper(I) neocuproine complexes have been widely studied, e.g. for the preparation of [catenane](/source/Catenane) and [rotaxane](/source/Rotaxane) complexes.[4] The copper-catalyzed release of NO+ ([nitrosonium](/source/Nitrosonium)) from [S-Nitrosothiols](/source/S-Nitrosothiol) is inhibited by neocuproine.[5]

Relative to 1,10-[phenanthroline](/source/Phenanthroline), neocuproine bears steric bulk flanking the nitrogen donor sites. A major consequence is that complexes of the type [M(neocuproine)3]n+ are disfavored, in contrast to the situation with phenanthroline ligands that lack substitution in the 2,9 positions.[6] The ligand [bathocuproine](/source/Bathocuproine) is similar to neocuproine, but has phenyl substituents at the 4,7-positions.

## Other metals

Platinum forms the square planar complexes [PtX2(2,9-dimethyl-1,10-phenanthroline)].[7]

Neocuproine has also been discovered to have properties that cause fragmentation and disappearance of the [melanin](/source/Melanin) in adult [zebrafish](/source/Zebrafish) [melanocytes](/source/Melanocytes). Those expressing eGFP also have been observed to lose eGFP [fluorescence](/source/Fluorescence) in the presence of neocuproine.[8]

## References

1. M. K. Eggleston; P. E. Fanwick; A. J. Pallenberg; D. R. McMillin (1997). "A Twist on the Copper Center in the Crystal Structure of [Cu(dnpp)2]PF6 and the Charge-Transfer Excited State? (dnpp = 2,9-Dineopentyl-1,10-phenanthroline)". *Inorganic Chemistry*. **36** (18): 4007–4010. [doi:10.1021/ic970135e](https://doi.org/10.1021/ic970135e)

1. Chandler, Christopher J.; Deady, Leslie W.; Reiss, James A. (1981). "Synthesis of some 2,9-Disubstituted-1,10-phenanthrolines". *Journal of Heterocyclic Chemistry*. **18** (3): 599–601. [doi:10.1002/jhet.5570180332](https://doi.org/10.1002/jhet.5570180332)

1. O'Reilly, E. J. & Plowman, R. A. (1959). "Coordination Compounds of Substituted 1,10-Phenanthrolines and Related Dipyridyls". *Australian Journal of Chemistry*. **13** (1): 145–149. [doi:10.1071/CH9600145](https://doi.org/10.1071/CH9600145)

1. McCleverty, J; Meyer, T. J. "Phenanthroline Ligands" in Comprehensive Coordination Chemistry II, Vol. 1, **2004**, p.25-39.

1. Al-Sa’doni, H.H.; Megson, I.L.; Bisland, S.; Butler, A.R.; Flitney, F.W. Neocuproine, A Selective Cu(I) Chelator, and the relaxation of rat vascular smooth muscle by S-nitrosothiols. *[British Journal of Pharmacology](/source/British_Journal_of_Pharmacology)*, 121(6), **1997**, p.1047-1050. [doi:10.1038/sj.bjp.0701218](https://doi.org/10.1038/sj.bjp.0701218)

1. Pallenberg, A. J.; Marschner, T. M.; Barnhart, D. M. (1997). "Phenanthroline complexes of the d10 Metals Nickel(0), Zinc(II) and Silver(I)—Comparison to Copper(I) Species". *Polyhedron*. **16** (16): 2711–2719. [doi:10.1016/S0277-5387(97)00051-X](https://doi.org/10.1016/S0277-5387(97)00051-X)

1. Fanizzi, Francesco P.; Margiotta, Nicola; Lanfranchi, Maurizio; Tiripicchio, Antonio; Pacchioni, Gianfranco; Natile, Giovanni "A Molecular Tool for Measuring the Electron-Acceptor Ability of Ligands from Crystallographic Data" *European Journal of Inorganic Chemistry* volume 8, **2004**, p.1705-1713. [doi:10.1002/ejic.200300888](https://doi.org/10.1002/ejic.200300888)

1. O’Reilly-Pol, Thomas; Johnson, Stephen L. "Neocuproine Ablates Melanocytes in Adult Zebrafish" *Zebrafish* 5(4). Mary Ann Liebert, Inc. **2008**. [doi:10.1089/zeb.2008.0540](https://doi.org/10.1089/zeb.2008.0540)

## Appendix: NMR Shifts

The following figures contain information on the [nuclear magnetic resonance](/source/Nuclear_magnetic_resonance) spectroscopic data of neocuproine (from Chandler et al.):

1H NMR Substituent Chemical Shift (δ ppm) H-3,8 7.45 H-4,7 8.03 H-5,6 7.65

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

---
Adapted from the Wikipedia article [Neocuproine](https://en.wikipedia.org/wiki/Neocuproine) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Neocuproine?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.