DIPICOLINIC ACID

DIPICOLINIC ACID

CAS Number: 499-83-2
Molecular Weight:167.12
Molecular Formula:C7H5NO4

Dipicolinic acid (pyridine-2,6-dicarboxylic acid or PDC and DPA) is a chemical compound which plays a role in the heat resistance of bacterial endospores. 
Dipicolinic acid is also used to prepare dipicolinato ligated lanthanide and transition metal complexes for ion chromatography.
2, 6-Pyridinedicarboxylic acid (dipicolinic acid) is a widely used building block in co-ordination and supramolecular chemistry. 
The author of this book discusses the co-ordination chemistry of several metal complexes with dipicolinic acid, Dipicolinic acids analogues, and derivatives as ligands.

Dipicolinic acid, Beauveria sp. is an amphoteric polar metabolite produced by many bacterial and fungal species. 
Prior to Dipicolinic acids discovery as a microbial metabolite, dipicolinic acid had long been recognized as a chelating agent for many metal ions. 
Wide distribution of dipicolinic acid among microbes makes it an important dereplication standard in discovery. 
Dipicolinic acid reaches high concentrations (~10% w/w) in Bacillus endospores aiding heat resistance and Dipicolinic acid is used in laboratories as a marker for the effectiveness of sterilization.

Dipicolinic acid (DPA) is a multi-functional agent for cosmetics, antimicrobial products, detergents, and functional polymers. 
The aim of this study was to design a new method for producing DPA from renewable material. 
The Bacillus subtilis spoVF operon encodes enzymes for DPA synthase and the part of lysine biosynthetic pathway. 
However, DPA is only synthesized in the sporulation phase, so the productivity of DPA is low level. 

Here, we report that DPA synthase was expressed in vegetative cells, and DPA was produced in the culture medium by replacement of the spoVFA promoter with other highly expressed promoter in B. subtilis vegetative cells, such as spoVG promoter. 
DPA levels were increased in the culture medium of genetically modified strains. 
DPA productivity was significantly improved up to 29.14 g/L in 72 h culture by improving the medium composition using a two-step optimization technique with the Taguchi methodology.

Dipicolinic Acid is a chemical compound which composes 5% to 15% of the dry weight of bacterial spores. 
Dipicolinic acid forms a complex with calcium ions within the endospore core. 
This complex binds free water molecules, causing dehydration of the spore. 
As a result, the heat resistance of macromolecules within the core increases. 
The calcium-dipicolinic acid complex also functions to protect DNA from heat denaturation by inserting itself between the nucleobases, thereby increasing the stability of DNA. 
Dipicolinic acid is also used to prepare transition metal complexes for ion chromatography.

Preferred IUPAC name: Pyridine-2,6-dicarboxylic acid
Other names: 2,6-Pyridinedicarboxylic acid

Dipicolinic acid (DPA) is a major constituent of bacterial endospores and the thermal resistance of spores is closely correlated with their calcium dipicolinate content. 
The biosynthesis of DPA in anaerobes was studied in Cl. roseum using the technique of endotrophic sporulation. 
The cells from the complex medium were harvested at a stage when they were refractile and stainable, resuspended in nongrowth promoting mineral water supplemented with radioactive presumptive precursors of DPA and incubated. 
The incorporation in DPA of exogenously supplied individual metabolites was followed by radioactictivity (C14) measurements. 
Glutamic acid, aspartic acid, alanine, serine, and acetate were found efficient precursors of DPA.

CAS Number: 499-83-2
CHEBI: 46837 
ChEMBL:    ChEMBL284104 
ChemSpider: 9940
DrugBank: DB04267 
ECHA InfoCard: 100.007.178 Edit this at Wikidata
PubChem CID: 10367
UNII: UE81S5CQ0G 
CompTox Dashboard: (EPA) DTXSID7022043

Dipicolinic acid (DPA) comprises ∼10% of the dry weight of spores of Bacillus species. 
Although DPA has long been implicated in spore resistance to wet heat and spore stability, definitive evidence on the role of this abundant molecule in spore properties has generally been lacking. 
Bacillus subtilis strain FB122 (sleB spoVF) produced very stable spores that lacked DPA, and sporulation of this strain with DPA yielded spores with nearly normal DPA levels. 
DPA-replete and DPA-less FB122 spores had similar levels of the DNA protective α/β-type small acid-soluble spore proteins (SASP), but the DPA-less spores lacked SASP-γ. 
The DPA-less FB122 spores exhibited similar UV resistance to the DPA-replete spores but had lower resistance to wet heat, dry heat, hydrogen peroxide, and desiccation. 

Alternate Names:Dipicolinate; 2,6-Dicarboxypyridine; 2,6-Pyridinedicarboxylic acid
Application:Dipicolinic acid, Beauveria sp. is a useful chelating agent for many metal ions
CAS Number:499-83-2
Molecular Weight:167.12
Molecular Formula:C7H5NO4

Dipicolinic acid (DPA) is a unique constituent of endospores of Bacillus and Clostridium genuses and is also produced and secreted by certain Penicillium strains and by several entomopathogenic fungi. 
DPA and its derivatives show various biological activities including significant antimicrobial and antioxidant properties. 
As a strong complexing agent DPA is a potent metal-chelator functioning as a multidentate ligand that inhibits lipid peroxidation and protects glutathione reductase from the copper-dependent inactivation. 
A structural combination of DPA core with other heterocyclic compounds has already proven to be an excellent tool for gaining antimicrobial and antioxidant activity. 
In this work, thiadiazole, triazole, thiazolidinone and oxadiazole moieties were combined with the DPA core in order to achieve the expected potent antimicrobial and/or antioxidant activity. 
Diverse biological and/or antioxidant properties of 1,3,4-thiadiazoles, triazoles, thiazolidinones, and oxadiazoles have been documented. 
Only a slight change in structural characteristics can have a great effect on antifungal and antioxidant activity. 
To date, derivatives of dipicolinic acid were described by Milway in 2003 and in our previous work on Schiff bases.

A Bacillus subtilis mutant is described which forms heat-resistant spores only in the presence of external dipicolinic acid (DPA). 
The mutation, dpa-1, is localized in a new sporulation locus, linked to pyrA. 
The dpa-1 strain is unable to synthesize DPA but can incorporate external DPA. 
The amount of DPA incorporated, the frequency of heat-resistant spores and their degree of resistance are all dependent on the concentration of external DPA. 
Spores of dpa-1 strains exhibit normal resistance to most chemicals, including octanol and chloroform, but not to ethanol, pyridine, phenol and trichloroacetic acid. 

Complete resistance to the latter group depends on DPA. 
DPA incorporation is slow and apparently requires an energy supply but not protein synthesis. 
Direct involvement of DPA in the heat-resistance of the spores is suggested. 
Thin sections of DPA-less spores exhibit clearly visible cytoplasmic membranes and ribosomes. 
These structures are absent or less visible in the core of spores obtained with added DPA.

Display Name: Pyridine-2,6-dicarboxylic acid
EC Number: 207-894-3
EC Name: Pyridine-2,6-dicarboxylic acid
CAS Number: 499-83-2
Molecular formula: C7H5NO4
IUPAC Name: pyridine-2,6-dicarboxylic acid

Neither wet heat nor hydrogen peroxide killed the DPA-less spores by DNA damage, but desiccation did. 
The inability to synthesize both DPA and most α/β-type SASP in strain PS3664 (sspA sspB sleB spoVF) resulted in spores that lost viability during sporulation, at least in part due to DNA damage. 
DPA-less PS3664 spores were more sensitive to wet heat than either DPA-less FB122 spores or DPA-replete PS3664 spores, and the latter also retained viability during sporulation. 
These and previous results indicate that, in addition to α/β-type SASP, DPA also is extremely important in spore resistance and stability and, further, that DPA has some specific role(s) in protecting spore DNA from damage. 
Specific roles for DPA in protecting spore DNA against damage may well have been a major driving force for the spore's accumulation of the high levels of this small molecule.

Delayed gate fluorescence detection of dipicolinic acid (DPA), a universal and specific component of bacterial spores, has been appraised for use in a rapid analytical method for the detection of low concentrations of bacterial spores. 
DPA was assayed by fluorimetric detection of its chelates with lanthanide metals. 
The influence of the choice and concentration of lanthanide and buffer ions on the fluorescence assay was studied as well as the effects of pH and temperature. 
The optimal system quantified the fluorescence of terbium monodipicolinate in a solution of 10 µM terbium chloride buffered with 1 M sodium acetate, pH 5.6 and had a detection limit of 2 nM DPA. 
This assay allowed the first real-time monitoring of the germination of bacterial spores by continuously quantifying exuded DPA. 
A detection limit of 104Bacillus subtilis spores ml–1 was reached, representing a substantial improvement over previous rapid tests.

Appearance: White or Off-White Crystalline Powder
Solubility: 0.25 gm in 10 ml of 95% ethanol soluble
Melting Point: 238.0° to 252.0° C
Water Content: 0.50% w/w Max.
Sulfated Ash: 0.10% w/w Max.

Heavy Metals:    
Chromium: 10 ppm Max.
Iron: 50 ppm Max.
Assay: 99.0% Min.

Biological role
Dipicolinic composes 5% to 15% of the dry weight of bacterial spores.
Dipicolinic acid has been implicated as responsible for the heat resistance of the endospore, although mutants resistant to heat but lacking dipicolinic acid have been isolated, suggesting other mechanisms contributing to heat resistance are at work.
Two genera of bacterial pathogens are known to produce endospores: the aerobic Bacillus and anaerobic Clostridium.

Dipicolinic acid forms a complex with calcium ions within the endospore core. 
This complex binds free water molecules, causing dehydration of the spore. 
As a result, the heat resistance of macromolecules within the core increases. 
The calcium-dipicolinic acid complex also functions to protect DNA from heat denaturation by inserting itself between the nucleobases, thereby increasing the stability of DNA.

Density: 1.6±0.1 g/cm3
Boiling Point: 463.7±30.0 °C at 760 mmHg
Melting Point: 248-250 °C (dec.)(lit.)
Molecular Formula: C7H5NO4
Molecular Weight: 167.119
Flash Point: 234.3±24.6 °C
Exact Mass: 167.021851
PSA: 87.49000
LogP: -0.83
Vapour Pressure: 0.0±1.2 mmHg at 25°C
Index of Refraction: 1.628
Water Solubility: 5 g/L (20 ºC)

The high concentration of DPA in and specificity to bacterial endospores has long made it a prime target in analytical methods for the detection and measurement of bacterial endospores. 
A particularly important development in this area was the demonstration by Rosen et al. of an assay for DPA based on photoluminescence in the presence of terbium, although this phenomenon was first investigated for using DPA in an assay for terbium by Barela and Sherry.
Extensive subsequent work by numerous scientists has elaborated on and further developed this approach.

Dipicolinic acid (DPA) and the Ca2+ complex of DPA (CaDPA) are well-known and are major chemical components of bacterial spores. 
DPA's native fluorescence is very weak and is thought to be completely masked by the fluorescence of tryptophan when this compound is presented. 

Structure of dipicolinic acid (DPA). 
Note that, at physiological pH, the two carboxyl groups will be ionized and the resultant carboxylate groups can chelate divalent cations. 
Functional pyridine. 
Dipicolinic acid is used for transition metal ions, organic peroxides. 
Also be used as enzyme inhibitor in biochemistry. 
Dipicolinic acid is used as a bifunctional monomer and a pharmaceutical intermediate.

Molecular FormulaC7H5NO4
Average mass167.119 Da
Monoisotopic mass167.021851 Da
ChemSpider ID9940

Bacterial endospores are highly resistant structures and dipicolinic acid is a key component of their resilience and stability. 
Due to the difficulty in controlling endospore contaminants, they are of interest in clean rooms, food processing, and production industries, while benefical endospore-formers are sought for potential utility. 
Dipicolinic acid production has traditionally been recognized in Bacilli, Clostridia, and Paenibacilli. 
Here, sixty-seven strains of aerobic and anaerobic endospore-forming bacteria belonging to the genera Bacillus, Brevibacillus, Clostridium, Fontibacillus, Lysinibacillus, Paenibacillus, Rummeliibacillus, and Terribacillus were grown axenically and sporulated biomasses were assayed for dipicolinic acid production using fluorimetric detection. 
Strains testing positive were sequenced and the genomes analyzed to identify dipicolinic acid biosynthesis genes. 

The well-characterized biosynthesis pathway was conserved in 59 strains of Bacilli and Paenibacilli as well as two strains of Clostridia; six strains of Clostridia lacked homologs to genes recognized as involved in dipicolinic acid biosynthesis. 
Our results confirm dipicolinic acid production across different classes and families of Firmicutes. 
We find that members of Clostridium (cluster I) lack recognized dipicolinic acid biosynthesis genes and propose an alternate genetic pathway in these strains. 
Finally, we explore why the extent and mechanism of dipicolinic acid production in endospore-forming bacteria should be fully understood. 
We believe that understanding the mechanism by which dipicolinic acid is produced can expand the methods to utilize endospore-forming bacteria, such as novel bacterial strains added to products, for genes to create inputs for the polymer industry and to be better equipped to control contaminating spores in industrial processes.

Dipicolinic acid CAS Number: 499-83-2
Dipicolinic acid Molecular Formula: C7H5NO4
Dipicolinic acid Molecular Weight: 167.12
Dipicolinic acid Beilstein Registry Number: 131629
Dipicolinic acid EC Number: 207-894-3

Aqueous solutions of the calcium and sodium salts of dipicolinic acid (DPA) were shown to have weak fluorescence when excited at wavelengths near 300nm, but no fluorescence was observed from DPA alone. 
Upon UV irradiation at 254nm the fluorescence of all three forms increases dramatically. 
The emission spectrum of calcium-DPA (CaDPA) has a maximum at 406nm with full width at half-maximum of 70nm. 
Changes in the absorption spectrum of the irradiated solution and the fact that the changes neither in absorption nor in fluorescence reverse after several days in the dark indicate that a photochemical reaction has taken place. 
The shapes of the emission spectra for all three DPA forms were very close to identical for excitation wavelengths in the range of 270 to 310 nm and for UV irradiation up to three hours, suggesting that one particular photoproduct dominates in producing the enhanced fluorescence. 
Index Headings: Dipicolinic acid; Calcium dipicolinate; Fluorescence spectroscopy; Photochemical reaction.

The historical use of bacterial spores for biological warfare and the recent terrorism attacks are a concern for national security, pointing to the need for rapid analysis and detection of unknown chemical and biological agents. 
A major component of bacterial spores is dipicolinic acid (DPA) and its various salts such as calcium dipicolinate (CaDPA), which can contribute up to 17% of the dry weight of the spores. 
This fact motivates our study of DPA because Dipicolinic acid is a ready-made marker for endospores.

Although many laser spectroscopic techniques have been successfully applied in chemistry and biology, not all of them are practical for detection purposes. 
Methods based on fluorescence spectroscopy are not effective because the fluorescence signal does not usually offer adequate selectivity. 
Although a spontaneous Raman signal can be very selective, and has been successfully used for detection of DPA, Dipicolinic acid is often very weak and requires long acquisition times.

Synonyms:
2,6-Pyridinedicarboxylic acid
499-83-2
PYRIDINE-2,6-DICARBOXYLIC ACID
Dipicolinic acid
2,6-Dipicolinic acid
Dipicolinate
2,6-Dicarboxypyridine
MFCD00006299
UNII-UE81S5CQ0G
2,6-pyridinedicarboxylate
DPAC
UE81S5CQ0G
CHEMBL284104
2,6-pyridine dicarboxylic acid
CHEBI:46837
2,6-Pyridinedicarboxylic acid, 99%
2,6-pyridinedicarboxylic acid (dipicolinic acid)
NSC 176
EINECS 207-894-3
pyridine-2
pydcH2
PubChem8067
4ih3
ACMC-20aiw4
pyridine carboxylate, 6d
DSSTox_CID_2043
DSSTox_RID_76466
DSSTox_GSID_22043
Oprea1_533632
SCHEMBL34595
MLS000080748
pyridine-2,6-dicarboxlic acid
ARONIS021542
IFLab1_001781
NSC176
DTXSID7022043
BDBM26116
2,6-DI-CARBOXY-PYRIDINE
NSC-176
Pyridinedicarboxylic acid-(2,6)
HMS1417A21
HMS2231H20
ZINC105246
ACN-S002679
ACT07463
Tox21_301129
AC-704
ANW-75410
BBL012080
CCG-44216
CL0252
SBB028480
STK092939
AKOS000112829
AM82010
DB04267
MCULE-1484050836
PS-8736
NCGC00071864-02
NCGC00255028-01
AK-49834
CAS-499-83-2
SMR000034075
ST040658
SY001460
131629 [Beilstein]
2,6-Dipicolinic acid
2,6-Pyridindicarbonsäure [German] [ACD/IUPAC Name]
2,6-PYRIDINE DICARBOXYLIC ACID
2,6-Pyridinedicarboxylic acid [ACD/Index Name] [ACD/IUPAC Name]
2,6-Pyridinedicarboxylic acid solution
207-894-3 [EINECS]
499-83-2 [RN]
Acide 2,6-pyridinedicarboxylique [French] [ACD/IUPAC Name]
acide pyridine-2,6-dicarboxylique [French]
Dipicolinic acid [Wiki]
Dipicolinic acid solution
DPA
DPAC
Pyridine-2,6-dicarboxylic acid
T6NJ BVQ FVQ [WLN]
UE81S5CQ0G
[499-83-2]
2, 6-Pyridinedicarboxylic acid
2,6-Dicarboxypyridine
2,6-DI-CARBOXY-PYRIDINE
2,6-Pyridine-Dicarboxylic Acid
2,6-Pyridinedicarboxylic acid (Dipicolinic acid)
2,6-Pyridinedicarboxylic Acid (en)
2,6-pyridinedicarboxylic acid 98%
2,6-Pyridinedicarboxylic acid concentrate
2,6-pyridinedicarboxylic acid, 99%
2,6-pyridinedicarboxylic acid,99%
2.6-吡啶二甲酸
95-68-1 [RN]
ARONIS021542
BR-49834
C7H5NO4
CHEBI:46837
EINECS 207-894-3
InChI=1/C7H5NO4/c9-6(10)4-2-1-3-5(8-4)7(11)12/h1-3H,(H,9,10)(H,11,12
L-042,134
MFCD00474575
Oprea1_533632
PDC
PS-8736
PY-7340
pyridine 2,6-dicarboxylic acid, ???98%
pyridine-2,6-dicarboxlic acid????????????
pyridine-2,6-dicarboxylic acid, 98%
Pyridine-2,6-dicarboxylic acid|2,6-Dipicolinic acid
SR-01000600024-2
UNII:UE81S5CQ0G
UNII-UE81S5CQ0G
DB-015930
A7431
CS-0016012
EU-0033484
FT-0610741
P0554
M-5988
Q417164
2,6-Pyridinedicarboxylic acid-2,6-dipicolinic acid
SR-01000600024-2
W-105996
L-042,134
Z57202012
B63A70CE-B9AB-4EA2-834A-6C7634226BB0
F0451-0137
2,6-Pyridinedicarboxylic acid, for ion chromatography, >=99.5% (T)
2,6-Pyridinedicarboxylic acid concentrate, 0.02 M C7H5NO4 in water (0.04N), for ion chromatography, eluent concentrate