1,10-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.

Phenanthroline

Names
Preferred IUPAC name 1,10-Phenanthroline[1]
Identifiers
CAS Number	66-71-7 Y monohydrate: 5144-89-8 (monohydrate) Y
3D model (JSmol)	Interactive image monohydrate: Interactive image
Beilstein Reference	126461
ChEBI	CHEBI:44975 Y
ChEMBL	ChEMBL415879 Y monohydrate: ChEMBL1255788
ChemSpider	1278 Y monohydrate: 19955
DrugBank	DB02365 Y
ECHA InfoCard	100.000.572
EC Number	200-629-2 monohydrate: 627-114-9
Gmelin Reference	4040
KEGG	C00604
PubChem CID	1318 monohydrate: 21226
RTECS number	SF8300000
UNII	W4X6ZO7939 Y monohydrate: KSX215X00E Y
UN number	2811
CompTox Dashboard (EPA)	DTXSID1025857
InChI InChI=1S/C12H8N2/c1-3-9-5-6-10-4-2-8-14-12(10)11(9)13-7-1/h1-8H Y Key: DGEZNRSVGBDHLK-UHFFFAOYSA-N Y InChI=1/C12H8N2/c1-3-9-5-6-10-4-2-8-14-12(10)11(9)13-7-1/h1-8H Key: DGEZNRSVGBDHLK-UHFFFAOYAW
SMILES c1cc2ccc3cccnc3c2nc1 monohydrate: C1=CC2=C(C3=C(C=CC=N3)C=C2)N=C1.O
Properties
Chemical formula	C12H8N2
Molar mass	180.21 g/mol
Appearance	colourless crystals
Density	1.31 g/cm3
Melting point	118.56 °C (245.41 °F; 391.71 K)[2]
Boiling point	409.2[2]
Solubility in water	high[2]
Solubility in other solvents	acetone, ethanol[2]
Acidity (pKa)	4.84 (phenH+)[2]
Hazards
Occupational safety and health (OHS/OSH):
Main hazards	mild neurotoxin, strong nephrotoxin, and powerful diuretic
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H301, H410
Precautionary statements	P264, P270, P273, P301+P310, P321, P330, P391, P405, P501
Related compounds
Related compounds	2,2'-bipyridine ferroin phenanthrene
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Abbreviated "phen", it is used as a ligand in coordination chemistry, forming strong complexes with most metal ions.^[3][4] 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.^[5] 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) with the advantage that the two nitrogen donors are preorganized for chelation. Phenanthroline is a stronger base than bipy. According to one ligand ranking scale, phen is a weaker donor than bipy.^[6]

Several homoleptic complexes are known of the type [M(phen)₃]²⁺. Particularly well studied is [Fe(phen)₃]²⁺, called "ferroin." It can be used for the photometric determination of Fe(II).^[7] 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.^[8] The pink complex [Ni(phen)₃]²⁺ has been resolved into its Δ and Λ isomers.^[9] The complex [Ru(phen)₃]²⁺ is bioactive.^[10]

Copper(I) forms [Cu(phen)₂]⁺, which is luminescent.^[11][12]

Bioinorganic chemistry

1,10-Phenanthroline is an inhibitor of metallopeptidases, with one of the first observed instances reported in carboxypeptidase A.^[13] 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.^[14]

Related phen ligands

A variety of substituted derivatives of phen have been examined as ligands.^[12][15] Substituents at the 2,9 positions confer protection for the attached metal, inhibiting the binding of multiple equivalents of the phenanthroline. Such bulky ligands also favor trigonal or tetrahedral coordination at the metal.^[16] 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(neocuproine)Cl₂]₂.^[17]

Basicities of 1,10-Phenanthrolines and 2,2'-Bipyridine^[18]

phen derivative	pKa	comment/alt. name	numbering scheme
1,10-phenanthroline	4.86	phen
2,2'-bipyridine	4.30	bipy
5-nitro-1,10-phenanthroline	3.57
2,9-dimethyl-1,10-phenanthroline	unknown	neocuproine[19][20]
2,9-Dimethyl-4,7-diphenylphenanthroline	unknown	Bathocuproine[19][21]
4,7-dimethyl-1,10-phenanthroline	5.97
4,7-diphenyl-1,10-phenanthroline	unknown	bathophenanthroline[22]
5,6-dimethyl-1,10-phenanthroline	5.20	5,6-Me2phen
3,4,7,8-tetramethylphenanthroline	6.31	3,4,7,8-Me4phen[23]
4,7-dimethoxy-1,10-phenanthroline	6.45	4,7-(MeO)2phen[24]
2,6-dimesitylphenanthroline	unknown	HETPHEN[25][16]

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.^[26] Grignard reagents may be similarly titrated.^[27]

See also

• Ferroin – Complex of Fe²⁺ by ortho-phenanthroline

References

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2. Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 3.444. ISBN 978-1-4987-5429-3.
3. Luman, C.R. and Castellano, F.N. (2003) "Phenanthroline Ligands" in Comprehensive Coordination Chemistry II. Elsevier. ISBN 978-0-08-043748-4.
4. Sammes, Peter G.; Yahioglu, Gokhan (1994). "1,10-Phenanthroline: A versatile ligand". Chemical Society Reviews. 23 (5): 327. doi:10.1039/cs9942300327.
5. Halcrow, Barbara E.; Kermack, William O. (1946). "43. Attempts to find new antimalarials. Part XXIV. Derivatives of o-phenanthroline (7 : 8 : 3′ : 2′-pyridoquinoline)". J. Chem. Soc.: 155–157. doi:10.1039/jr9460000155. PMID 20983293.
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8. Bellér, G. B.; Lente, G. B.; Fábián, I. N. (2010). "Central Role of Phenanthroline Mono-N-oxide in the Decomposition Reactions of Tris(1,10-phenanthroline)iron(II) and -iron(III) Complexes". Inorganic Chemistry. 49 (9): 3968–3970. doi:10.1021/ic902554b. PMID 20415494.
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11. Armaroli N (2001). "Photoactive Mono- and Polynuclear Cu(I)-Phenanthrolines. A Viable Alternative to Ru(Ii)-Polypyridines?". Chemical Society Reviews. 30 (2): 113–124. doi:10.1039/b000703j.
12. Pallenberg A. J.; Koenig K. S.; Barnhart D. M. (1995). "Synthesis and Characterization of Some Copper(I) Phenanthroline Complexes". Inorganic Chemistry. 34 (11): 2833–2840. doi:10.1021/ic00115a009.
13. Felber, Jean-Pierre; Coombs, Thomas L.; Vallee, Bert L. (1962). "The mechanism of inhibition of carboxypeptidase A by 1,10-phenanthroline". Biochemistry. 1 (2): 231–238. doi:10.1021/bi00908a006. PMID 13892106.
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16. Somerville, Rosie J.; Odena, Carlota; Obst, Marc F.; Hazari, Nilay; Hopmann, Kathrin H.; Martin, Ruben (2020). "Ni(I)–Alkyl Complexes Bearing Phenanthroline Ligands: Experimental Evidence for CO2 Insertion at Ni(I) Centers". Journal of the American Chemical Society. 142 (25): 10936–10941. Bibcode:2020JAChS.14210936S. doi:10.1021/jacs.0c04695. PMC 7351122. PMID 32520556.
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24. Altman, Ryan A. (2008). "1,10-Phenanthroline, 4,7-Dimethoxy". Encyclopedia of Reagents for Organic Synthesis. eEROS. doi:10.1002/047084289X.rn00918. ISBN 978-0-471-93623-7.
25. Kohler, Lars; Hayes, Dugan; Hong, Jiyun; Carter, Tyler J.; Shelby, Megan L.; Fransted, Kelly A.; Chen, Lin X.; Mulfort, Karen L. (2016). "Synthesis, structure, ultrafast kinetics, and light-induced dynamics of CuHETPHEN chromophores". Dalton Transactions. 45 (24): 9871–9883. doi:10.1039/c6dt00324a. PMID 26924711.
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