3-Hydroxyisonicotinaldehyde

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| ImageFile = 3-Hydroxyisonicotinaldehyde.svg

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| PIN = 3-Hydroxyisonicotinaldehyde

| OtherNames = 3-Hydroxy-4-pyridinecarboxaldehyde

|Section1 ={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 167264

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C6H5NO2/c8-4-5-1-2-7-3-6(5)9/h1-4,9H

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| StdInChIKey = NVLPDIRQWJSXLZ-UHFFFAOYSA-N

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| CASNo= 1849-54-3

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| EINECS = 810-332-5

| PubChem= 192747

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| SMILES = c1cncc(c1C=O)O

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|Section2 ={{Chembox Properties

| Properties_ref = {{cite journal |doi=10.1016/S0040-4020(01)82610-7 |title=Studies on pyridoxine and pyridoxal analogs—I |year=1958 |last1=Heinert |first1=Dietrich |last2=Martell |first2=Arthur E. |journal=Tetrahedron |volume=3 |pages=49–61 }}

| C=6 | H=5 | N=1 | O=2

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| Density= 1.327 g/cm3

| MeltingPtC = 126-128

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|Section3 ={{Chembox Hazards

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| HPhrases = {{H-phrases|302|315|319|H335}}

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3-Hydroxyisonicotinaldehyde (HINA), also known as 3-hydroxypyridine-4-carboxaldehyde, is a derivative of pyridine, with hydroxyl and aldehyde substituents. It has been studied as a simple analogue of vitamin B6. In 2020, it was reported as having the lowest molecular weight of all dyes which exhibit green fluorescence.{{cite web |url=https://www.chemistryworld.com/news/fluorescent-molecule-breaks-size-record-for-green-emitting-dyes/4012911.article |title=Fluorescent molecule breaks size record for green-emitting dyes |last=Cozens |first=Tom |website=chemistryworld.com |date=2020-12-16 |access-date=2021-12-03 }}{{cite journal |doi=10.1039/d0sc05557c |title=Discovery of a size-record breaking green-emissive fluorophore: Small, smaller, HINA |year=2021 |last1=Kang |first1=Rui |last2=Talamini |first2=Laura |last3=d'Este |first3=Elisa |last4=Estevão |first4=Bianca Martins |last5=De Cola |first5=Luisa |last6=Klopper |first6=Wim |last7=Biedermann |first7=Frank |journal=Chemical Science |volume=12 |issue=4 |pages=1392–1397 |pmid=34163902 |pmc=8179180 }}

Preparation

3-Hydroxyisonicotinaldehyde was first prepared in 1958 by oxidation of 3-hydroxy-4-pyridinemethanol with manganese dioxide. Alternative syntheses have also been reported.{{cite journal |doi=10.1021/jm00290a026 |title=Vitamin B6 analogs. Improved synthesis of 3-hydroxypyridine-4-carboxaldehyde |year=1971 |last1=O'Leary |first1=Marion H. |last2=Payne |first2=James R. |journal=Journal of Medicinal Chemistry |volume=14 |issue=8 |pages=773–774 |pmid=5114077 }}{{cite journal |doi=10.1016/0304-5102(91)85059-B |title=Vapour phase oxidation in the preparation of 3-hydroxypyridine-4-carboxaldehyde: The vitamin B6 analog |year=1991 |last1=Prasad |first1=A.R. |last2=Subrahmanyam |first2=M. |journal=Journal of Molecular Catalysis |volume=65 |issue=3 |pages=L25–L27 }}

Spectroscopic properties

The absorption spectrum of HINA has been the subject of studies dating back to the 1950s, owing to its relationship to vitamin B6 and pyridoxal, of which it is a simple analogue.{{cite journal |doi=10.1021/ja01531a006 |title=Pyridoxine and Pyridoxal Analogs. IV. Ultraviolet Spectra and Solution Equilibria of 3-Methoxypyridine-2(and 4-)-aldehydes and of 3-Hydroxypyridine-2 (and 4-)-aldehydes |year=1959 |last1=Nakamoto |first1=Kazuo |last2=Martell |first2=A. E. |journal=Journal of the American Chemical Society |volume=81 |issue=22 |pages=5863–5869 }}{{cite journal |doi=10.1021/bi00747a031 |title=Comparison of the rate constants for general base catatlyzed prototropy and racemization of the aldimine species formed from 3-hydroxypyridine-4-carboxaldehyde and alanine |year=1973 |last1=Dixon |first1=Jack E. |last2=Bruice |first2=Thomas C. |journal=Biochemistry |volume=12 |issue=23 |pages=4762–4766 |pmid=4773854 }}{{cite journal |doi=10.1016/0304-4165(76)90284-1 |title=Band-shape analysis and resolution of electronic spectra of pyridoxal phosphate and other 3-hydroxypyridine-4-aldehydes |year=1976 |last1=Harris |first1=C. |last2=Johnson |first2=R. |last3=Metzler |first3=D. |journal=Biochimica et Biophysica Acta (BBA) - General Subjects |volume=421 |issue=2 |pages=181–194 |pmid=1252466 }}{{cite journal |doi=10.1016/j.tet.2004.10.036 |title=Synthesis and spectroscopic properties of Schiff bases derived from 3-hydroxy-4-pyridinecarboxaldehyde |year=2005 |last1=Sanz |first1=Dionisia |last2=Perona |first2=Almudena |last3=Claramunt |first3=Rosa M. |last4=Elguero |first4=José |journal=Tetrahedron |volume=61 |pages=145–154 }} However, its fluorescent properties were not described until 2020. It is noteworthy for having a green-emitting fluorophore with a wavelength of maximum emission (λem,max) at 525 nm in aqueous solution at alkaline pH, making it the compound of lowest molecular weight to display that property. In acidic solutions, the fluorescence is less intense and becomes blue; the compound has isosbestic points at 270 and 341 nm.

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The molecular basis of the observed properties is the presence of a push-pull fluorophore, a feature of many fluorescent and luminescent compounds.{{cite book |isbn=978-1118175866|title=Fluorescent Analogs of Biomolecular Building Blocks: Design and Applications|editor1-first=Marcus |editor1-last=Wilhelmsson |editor2-first=Yitzhak|editor2-last=Tor|date=2016-04-16|publisher=Wiley|pages=257–280}} At pH above 7.1 in aqueous solutions, HINA is in its anionic form, with its absorbance peak at 385 nm and emission peak at 525 nm. The anion contains just 13 atoms, with a molecular mass of 122 Da. The quantum yield for the emission is 15%, with an emission lifetime of 1.0 ns. The observed Stokes shift of 6900 cm−1 is typical of push-pull dyes.

Uses

=In mechanistic studies of vitamin B<sub>6</sub>=

{{See|Pyridoxal phosphate#Catalytic mechanism}}

HINA has been used as an analogue of pyridoxal 5′-phosphate, the active form of the coenzyme vitamin B6. It is an especially good mimic for the enzyme-bound form of that compound, better than the vitamin or pyridoxal.{{cite journal |doi=10.1021/bi00877a014 |title=Catalytic Reactions Involving Azomethines. V. Rates and Equilibria of Imine Formation with 3-Hydroxypyridine-4-aldehyde and Amino Acids |year=1965 |last1=French |first1=Thayer C. |last2=Auld |first2=David S. |last3=Bruice |first3=Thomas C. |journal=Biochemistry |volume=4 |pages=77–84 |pmid=14285248 }} The enzyme mechanism involves imine formation, giving a Schiff's base, and such derivatives of HINA with amino acids have been studied for their reaction kinetics, leading to insights about the enzymes which use pyridoxal 5-phosphate.{{cite journal |doi=10.1016/0003-9861(70)90340-1 |title=Catalytic reactions involving azomethines. XII. Transamination of 1-methyl-3-hydroxy-4-formylpyridinium chloride |year=1970 |last1=Maley |first1=John R. |last2=Bruice |first2=Thomas C. |journal=Archives of Biochemistry and Biophysics |volume=136 |issue=1 |pages=187–192 |pmid=5417614 }}{{cite journal | doi = 10.1146/annurev.biochem.73.011303.074021| title = Pyridoxal Phosphate Enzymes: Mechanistic, Structural, and Evolutionary Considerations| year = 2004| last1 = Eliot| first1 = Andrew C.| last2 = Kirsch| first2 = Jack F.| journal = Annual Review of Biochemistry| volume = 73| pages = 383–415| pmid = 15189147}}

=As a dyestuff=

File:HINA fluorophore.jpg

Stable dyes of low molecular weight which are water soluble are useful in biological systems.{{cite journal |doi= 10.1039/C1CS15126F |title= Chemistry and applications of flavylium compounds: A handful of colours |year= 2012 |last1= Pina |first1= Fernando |last2= Melo |first2= Maria J. |last3= Laia |first3= César A. T. |last4= Parola |first4= A. Jorge |last5= Lima |first5= João C. |journal=Chemical Society Reviews |volume= 41 |issue= 2 |pages= 869–908 |pmid= 21842035 }}{{cite journal |doi=10.1146/annurev-biochem-061516-044839 |title=Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines |year=2017 |last1=Lavis |first1=Luke D. |journal=Annual Review of Biochemistry |volume=86 |pages=825–843 |pmid=28399656 |doi-access=free }} HINA has been used to detect and quantify the presence of cysteine in aqueous solutions.

References

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Category:Hydroxypyridines

Category:Aldehydes

Category:Fluorescent dyes