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Dipicolinic acid
Dipicolinic acid
Dipicolinic acid
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Dipicolinic acid[1]
Names
Preferred IUPAC name
Pyridine-2,6-dicarboxylic acid
Other names
2,6-Pyridinedicarboxylic acid
Identifiers
3D model (JSmol)
131629
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.007.178 Edit this at Wikidata
EC Number
  • 207-894-3
50798
UNII
  • InChI=1S/C7H5NO4/c9-6(10)4-2-1-3-5(8-4)7(11)12/h1-3H,(H,9,10)(H,11,12) checkY
    Key: WJJMNDUMQPNECX-UHFFFAOYSA-N checkY
  • InChI=1/C7H5NO4/c9-6(10)4-2-1-3-5(8-4)7(11)12/h1-3H,(H,9,10)(H,11,12)
    Key: WJJMNDUMQPNECX-UHFFFAOYAM
  • c1cc(nc(c1)C(=O)O)C(=O)O
Properties
C7H5NO4
Molar mass 167.120 g·mol−1
Melting point 248 to 250 °C (478 to 482 °F; 521 to 523 K)
Hazards
GHS labelling:[2]
GHS07: Exclamation mark
Warning
H315, H319, H335
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

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. It is also used to prepare dipicolinato ligated lanthanide and transition metal complexes for ion chromatography.[1]

Biological role

[edit]

Dipicolinic acid composes 5% to 15% of the dry weight of Bacillus subtilis spores.[3][4] It has been implicated as responsible for the heat resistance of the endospore,[3][5] although mutants resistant to heat but lacking dipicolinic acid have been isolated, suggesting other mechanisms contributing to heat resistance are at work.[6] Two genera of bacterial pathogens are known to produce endospores: the aerobic Bacillus and anaerobic Clostridium.[7]

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.[8]

Detection

[edit]

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,[9] although this phenomenon was first investigated for using DPA in an assay for terbium by Barela and Sherry.[10]

Environmental behavior

[edit]

Simple substituted pyridines vary significantly in environmental fate characteristics, such as volatility, adsorption, and biodegradation.[11] Dipicolinic acid is among the least volatile, least adsorbed by soil, and most rapidly degraded of the simple pyridines.[12] A number of studies have confirmed dipicolinic acid is biodegradable in aerobic and anaerobic environments, which is consistent with the widespread occurrence of the compound in nature.[13] With a high solubility (5g/liter) and limited sorption (estimated Koc = 1.86), utilization of dipicolinic acid as a growth substrate by microorganisms is not limited by bioavailability in nature.[14]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Dipicolinic acid

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from Grokipedia
Dipicolinic acid, systematically named pyridine-2,6-dicarboxylic acid, is an with the molecular formula C₇H₅NO₄ that functions as a major in bacterial endospores, comprising approximately 10% of their dry weight and playing a critical role in their resistance to extreme environmental stresses such as heat and . Chemically, dipicolinic acid features a ring substituted with groups at the 2- and 6-positions, resulting in a of 167.12 g/mol and a of 248–250 °C with . It exhibits chelating properties, forming stable 1:1 complexes with divalent cations like calcium (Ca²⁺), which is essential for its biological function. In laboratory settings, it is utilized as a chelating agent in , , and pharmaceutical synthesis due to its ability to bind metal ions effectively. In , dipicolinic acid is predominantly found in the core of endospores produced by such as Bacillus and Clostridium species, where it exists primarily as a calcium dipicolinate (Ca-DPA) chelate that accounts for about 20% of the core's dry weight. This chelate lowers the water content in the core, enhancing resistance to wet heat, dry heat, oxidative damage from , and by protecting DNA from harm. lacking dipicolinic acid demonstrate significantly reduced viability and stability, with increased sensitivity to these stresses, underscoring its indispensable role in and survival. Additionally, dipicolinic acid facilitates by activating cortex-lytic enzymes like CwlJ.

Chemical Properties

Molecular Structure

Dipicolinic acid, systematically named pyridine-2,6-dicarboxylic acid, is commonly abbreviated as DPA or PDC. Its molecular formula is C₇H₅NO₄, corresponding to a of 167.12 g/mol. The core structure features a six-membered heterocycle with (-COOH) substituents at the 2- and 6-positions, symmetric relative to the ring . This arrangement positions the carboxyl groups ortho to the , facilitating intramolecular hydrogen bonding in certain tautomers and promoting planarity across the molecule. The ring maintains aromatic character through delocalized π-electrons, with the atom contributing one to the aromatic while its remains in an sp² orbital orthogonal to the π-system. Computational studies at the B3LYP/6-31G(d) level reveal typical bond lengths in the ring: C-N ≈ 1.34 and C-C ≈ 1.39–1.41 , with internal angles close to 120° for all stable isomers. The carboxyl groups exhibit between the C=O (≈1.21 ) and C-O (≈1.36 ) bonds, conjugated with the ring via shortened ipso C-C bonds (≈1.47 ), which enhances electron withdrawal from the substituents. This conjugation stabilizes the planar conformation observed in all low-energy gas-phase isomers, with dihedral angles between the carboxyl planes and ring near 0°. Experimental structures of the monohydrate confirm near-planarity of the core scaffold, though hydrogen bonding with slightly perturbs the carboxyl orientations. Compared to (benzene-1,2-dicarboxylic acid), the in dipicolinic acid polarizes the π-electron distribution, rendering the ring more electron-deficient and increasing the acidity of the carboxyl protons (pKₐ values ≈ 2.1 and 4.8 versus 2.9 and 5.4 for ). This effect promotes greater planarity by reducing steric repulsion in the ortho positions and enhances delocalization, influencing the at the carboxyl oxygens for potential bidentate .

Physical Properties

Dipicolinic acid appears as a crystalline solid at . Its is 167.12 g/mol. The compound has a of 248–250 °C, at which it decomposes without a distinct phase. It does not have a reported under standard conditions due to , though estimated values range from 295 °C to 464 °C based on computational models. The is approximately 1.52 g/cm³, derived from structural estimates. Dipicolinic acid exhibits high solubility in water, with a value of 5 g/L at 20 °C, and is soluble in alkaline solutions where it forms soluble salts. It is insoluble in non-polar solvents such as hydrocarbons, consistent with its polar nature. The high water solubility arises from the polar carboxyl groups in its molecular structure. As a , dipicolinic acid displays acidic behavior with pKa values of 2.16 (first carboxyl group) and 4.76 (second carboxyl group) at 25 °C, facilitating proton donation in aqueous environments.

Chemical Reactivity

Dipicolinic acid, a diprotic , undergoes stepwise of its two carboxylic groups to form mono- and di-anionic , with reported pKa values of 2.07 and 4.66 at 25°C, respectively. These acid-base reactions enable the molecule to exist predominantly as the di-anion under neutral or basic conditions, facilitating its role in subsequent chemical interactions. The process is influenced by the proximity of the carboxylic groups to the , which moderately affects the acidity compared to isolated derivatives. In coordination chemistry, dipicolinic acid demonstrates bidentate ligand capability through its two carboxyl groups, forming stable chelates with transition metals, lanthanides, and alkaline earth metals such as calcium, though it typically coordinates in a tridentate fashion involving the nitrogen as well. For instance, the 1:1 calcium-dipicolinate complex [Ca(DPA)] exhibits a stability constant of log K = 4.39, highlighting the robustness of these interactions in aqueous solutions. Such metal-DPA complexes are employed in to separate high-valence metal cations by dynamically modifying neutral resins, where the chelates enhance selectivity and retention. Dipicolinic acid undergoes thermal decomposition upon heating, with decarboxylation occurring at approximately 252°C, yielding gaseous products including CO₂ and pyridine as primary fragments. This pathway reflects the molecule's susceptibility to high-temperature breakdown at the carboxylic sites while preserving the aromatic core. Additionally, the aromatic stability of the pyridine ring confers redox inactivity to dipicolinic acid, preventing facile oxidation or reduction and contributing to the inertness of its metal complexes under ambient conditions.

Synthesis and Production

Biosynthetic Pathways

Dipicolinic acid (DPA) is primarily synthesized by endospore-forming bacteria in the genera Bacillus and Clostridium during the sporulation phase of their life cycle. This process is essential for spore maturation, with DPA accumulating in the spore core to high concentrations. The biosynthetic pathway of DPA diverges from the lysine biosynthesis route, starting from L-aspartate. Aspartokinase (e.g., LysC) first phosphorylates L-aspartate to L-4-aspartyl phosphate, which is then reduced to L-aspartate-β-semialdehyde by aspartate-β-semialdehyde dehydrogenase (Asd). Dihydropicolinate synthase (DapA) subsequently condenses L-aspartate-β-semialdehyde with pyruvate to form (S)-2,3-dihydropicolinate. The terminal step is catalyzed by DPA synthase, a complex of SpoVFA and SpoVFB proteins encoded by the spoVF operon in Bacillus subtilis, which converts the intermediate to DPA. Biosynthesis is tightly regulated and occurs specifically during late sporulation stages, induced by nutrient starvation signals that activate the master regulator Spo0A, leading to transcription of the spoVF in the mother cell. In mature Bacillus subtilis spores, DPA constitutes 5–15% of the total dry weight. Recent has extended DPA production to non-native hosts for industrial applications. In Escherichia coli, co-expression of Bacillus subtilis genes (lysC, asd, dapA, spoVFA, spoVFB) with knockouts of competing pathways (lysA, tdh, metA) yielded up to 5.21 g/L DPA from supplemented aspartate or 4.7 g/L from glucose. In Corynebacterium glutamicum, a lysine-overproducing strain engineered with dpaAB from Paenibacillus sonchi and CRISPRi optimizations for flux redirection produced 2.5 g/L DPA in shake flasks and 1.5 g/L in fed-batch fermentations using renewable feedstocks like . Engineering efforts in the native host have also advanced DPA production as of November 2025. By overexpressing the spoVF operon and knocking out the spore coat assembly activator gerE, researchers achieved extracellular DPA titers of up to 944 mg/L in shake flasks and 1.25 g/L in optimized fed-batch fermentations in a 1.5 L . These modifications enhance flux toward DPA without sporulation, improving solubility and yield for precursor applications.

Chemical Synthesis Methods

Dipicolinic acid, also known as 2,6-pyridinedicarboxylic acid, is classically synthesized through the oxidation of 2,6-lutidine (2,6-dimethylpyridine) using as the oxidant. The process begins by dissolving 2,6-lutidine in dilute or , followed by gradual addition of aqueous KMnO₄ solution under conditions (approximately 100°C) to facilitate the stepwise oxidation of the methyl groups to carboxylic acids. This involves an initial formation of the mono-oxidized intermediate, 6-methylpyridine-2-carboxylic acid, which is further oxidized to the target diacid upon prolonged reaction or excess oxidant. The reaction mixture is then filtered to remove residues, acidified with to pH 2–3, and the product is isolated by cooling and recrystallization from hot , achieving yields of 64–70%. This permanganate-based route, first reported in detail in 1935, remains a benchmark for laboratory-scale preparation due to its simplicity and use of inexpensive reagents, though it generates significant inorganic waste and requires careful control to minimize side products like over-oxidation to pyridine derivatives. Challenges include poor selectivity in the multi-step oxidation, where incomplete conversion to the diacid can occur, necessitating excess KMnO₄ (typically 3–4 equivalents per ) and extended reaction times of 4–6 hours. Purification via recrystallization is essential to achieve high purity (>98%), as residual intermediates and salts can contaminate the product. Modern synthetic methods have improved efficiency and environmental compatibility through catalytic oxidations. One approach employs phase-transfer catalysis (PTC) with oxygen as the terminal oxidant: 2,6-lutidine is treated with tert-butoxide base in the presence of a PTC like benzyltriethylammonium chloride, under atmospheric oxygen at 25–50°C for 24 hours, yielding 69% of dipicolinic acid after acidification and extraction. This auto-oxidation avoids stoichiometric heavy metal oxidants, enhancing , though scalability is limited by the need for anhydrous conditions and base recycling. A more advanced industrial route utilizes liquid-phase with air or oxygen in water at 60–100°C for 2–4 hours, employing metal catalysts (e.g., or ) at 0.5–2.5 mol% loading, initiated by salts or persulfates. The reaction proceeds via radical mechanisms, selectively converting both methyl groups with minimal byproducts, followed by basification, acidification, and to yield 93–96% dipicolinic acid with >99% purity. This method addresses classical route limitations by reducing waste and energy use, making it suitable for large-scale production; however, recovery remains a key challenge for cost-effectiveness. Complementary bio-engineered approaches offer sustainable alternatives but are not detailed here.

Biological Role

Role in Bacterial Endospores

Dipicolinic acid (DPA) accumulates during the late stages of sporulation in such as and species, where it complexes with calcium ions (Ca²⁺) to form calcium dipicolinate (Ca-DPA), constituting up to 25% of the core's dry weight. This accumulation, which occurs after the formation of the cortex and forespore membrane, is essential for completing maturation and is tightly regulated by the proteins that facilitate DPA uptake into the developing core. The high concentration of Ca-DPA in the core, often reaching 10-15% of the total dry weight, plays a pivotal role in establishing the dormant state by binding free molecules and promoting . The primary mechanisms by which Ca-DPA contributes to endospore resilience involve core dehydration and biomolecular stabilization. By chelating Ca²⁺ and interacting with core components, Ca-DPA significantly reduces the water activity and content in the spore core, creating a low-moisture environment (a_w as low as 0.13 under certain conditions) that inhibits metabolic activity and enzymatic reactions during dormancy. Additionally, Ca-DPA stabilizes DNA through hydrogen bonding networks and by shielding it from oxidative damage and UV radiation, working in concert with small acid-soluble proteins (SASPs) to maintain genomic integrity under stress. This dehydrated, protected state is crucial for the spore's ability to withstand extreme conditions without loss of viability. Ca-DPA significantly enhances heat resistance, allowing endospores to survive temperatures of 100–120 °C for several minutes, far exceeding the tolerance of vegetative cells. Experimental studies with mutants defective in DPA synthesis (e.g., spoVF strains) demonstrate that the absence of DPA results in a 100-fold reduction in wet heat tolerance. These findings underscore DPA's indispensable role in thermal stability, as supplementation during sporulation restores resistance levels in such mutants. The incorporation of DPA into endospores has evolutionary significance, particularly for bacteria in the Firmicutes , where it enables long-term in harsh environments like hot springs, deserts, and deep subsurface habitats by conferring resistance to , , and temperature extremes. This trait likely provided a selective advantage, allowing spore-forming bacteria to colonize diverse and challenging niches over billions of years. During , the release of Ca-DPA from the core triggers water influx and activates cortex-lytic enzymes such as CwlJ, facilitating the transition from to vegetative growth.

Interactions with Metals and Biomolecules

Dipicolinic acid (DPA) acts as a tridentate chelator with ions such as Eu³⁺ and Tb³⁺, forming stable complexes that enhance through the in various non-spore biological applications. These complexes, such as Na₃[Eu(L)₃], exhibit improved quantum yields (up to 15.7%) and lifetimes (around 1 ms), enabling their use in for imaging cancer cells like T24, where they localize in perinuclear regions and nucleoli. Similarly, Tb³⁺-DPA systems show enhanced fluorescence lifetimes and intensities, facilitating cellular imaging in and HEK293T cells with endosomal/lysosomal targeting. DPA-containing lanthanide complexes demonstrate interactions with nucleic acids, including binding to double-stranded DNA and DNA hairpin loops, as observed in dinuclear Eu³⁺ helicates monitored via characteristic excitation peaks. These binding motifs, involving coordination through groups, mirror stabilization mechanisms seen in the Ca-DPA complex and suggest potential applications in modulating structures for research purposes. In non-sporulating and eukaryotes, DPA plays a minor role, primarily as a chelating agent analogous to siderophores for metal sequestration and . For instance, DPA derivatives inhibit metallo-β-lactamases in by chelating ions, thereby restoring efficacy without direct involvement in iron acquisition. In eukaryotic cells, DPA-lanthanide complexes support metal transport studies via , aiding intracellular without endogenous production. DPA exhibits low mammalian . It is also readily biodegradable under aerobic conditions, supporting its in biological contexts. Lanthanide-DPA complexes further show low , with IC₅₀ values above 500 μM in cell lines such as Jurkat and . Recent studies highlight DPA's utility in , particularly for engineering metal transport systems in non-native hosts. These applications leverage DPA's properties to design responsive biomaterials for controlled ion delivery in eukaryotic models.

Detection and Analysis

Spectroscopic Detection

Dipicolinic acid (DPA) exhibits characteristic absorption in the ultraviolet-visible (UV-Vis) region due to its ring structure, with peaks typically observed between 260 and 280 nm, shifting slightly with variations from the protonated to deprotonated forms. This absorption arises from π-π* transitions in the aromatic system, enabling straightforward identification in aqueous solutions via standard . Fourier-transform (FTIR) reveals key vibrational modes for DPA, including the characteristic C=O stretch of the carboxyl groups at approximately 1700 cm⁻¹, indicative of the functionality. () further confirms the structure, with ¹H NMR signals for the aromatic protons on the ring appearing in the 8–9 ppm range, reflecting their deshielded environment adjacent to the electron-withdrawing carboxyl groups. A prominent method for sensitive detection leverages the enhancement from metal , where DPA forms a ternary complex with (III) (Tb³⁺), enabling lanthanide-sensitized . This Tb(III)-DPA complex, facilitated by DPA's bidentate coordination to the metal, exhibits excitation at 270 nm and green emission at 545 nm, with a detection sensitivity reaching 10⁻⁹ M. The of DPA efficiently transfers energy to Tb³⁺, non-radiative decay pathways and amplifying the long-lived emission characteristic of lanthanides. In applications for detection, the ratiometric measurement of Tb-DPA emission intensity at 545 nm relative to at around 350 nm allows discrimination of endospores from vegetative cells or interferents, as spores uniquely release DPA upon while retaining intrinsic protein . Recent advancements have extended this approach to (Eu³⁺) complexes, utilizing the for enhanced sensitivity. A 2024 study demonstrated an Eu(III) that sensitizes Eu³⁺ emission through DPA coordination, achieving a limit of detection of 15.23 nM for DPA via enhancement at 618 nm upon excitation at 280 nm, with potential for rapid screening.

Biosensor-Based Methods

Biosensor-based methods for dipicolinic acid (DPA) detection utilize engineered recognition elements, such as , polymers, or chelating agents, integrated into compact devices to enable selective binding and . These approaches target DPA as a key for bacterial endospores, offering advantages in sensitivity, speed, and portability over traditional analytical techniques, particularly for on-site biothreat assessment. Nanomaterial sensors have emerged as versatile platforms for DPA detection, leveraging optical changes induced by specific binding. Gold nanoparticles (AuNPs) functionalized with lanthanide chelates, such as ethylenediamine-Eu³⁺ or Tb³⁺ complexes, facilitate fluorescent sensing through DPA coordination, which enhances emission via the antenna effect while providing ratiometric readout for improved accuracy; detection limits reach the nanomolar range with high selectivity against interfering aromatic compounds. Colorimetric variants employ Ca²⁺-complexed glutathione-capped AuNPs, where DPA reverses nanoparticle aggregation due to its stronger (formation constant log Kf = 4.4), producing a visible red-to-purple color shift detectable by eye or simple spectrometry, with a limit of detection of approximately 2 μM in complex samples like soil extracts from spores. Quantum dots further enhance portability; for example, MXene quantum dots (MQDs) conjugated with EDTA-Eu³⁺ enable ratiometric , where DPA triggers energy transfer to produce a blue-to-red emission shift (445 nm to 616 nm), achieving a solution-phase detection limit of 0.26 nM and smartphone-compatible test strips for field use with recoveries of 81–112% in water samples. Electrochemical sensors detect DPA through measurable perturbations in electrode interfaces upon or binding. Potentiometric devices, constructed via surface imprinting of DPA on electrodes, respond selectively to concentrations from 1.5 × 10⁻⁶ to 0.0194 M, with a 25-second response time for 4 × 10⁻⁴ M DPA and retention of 90% signal after 550 measurements, demonstrating robustness in biological matrices. Molecularly imprinted polymers (MIPs) incorporated into such sensors amplify selectivity by creating DPA-specific cavities, enabling reliable potentiometric detection in aqueous environments amid interferents like pyridinedicarboxylic acids. Impedance variants, such as MoS₂-terbium metal-organic framework nanocomposites on electrodes, quantify DPA via chelation-induced resistance changes, offering sensitive monitoring with electrochemical impedance shifts correlated to binding events. Integration with microfluidics streamlines these biosensors for rapid, automated processing. A smartphone-interfaced, 3D-printed combines Eu-MOF/carbon dot nanocomposites for dual-mode ( and colorimetric) DPA detection, exploiting lanthanide-DPA for transfer-based signaling; it achieves limits of detection of 0.04 μM () and 10.14 μM (colorimetric) within 5–10 minutes via pressure-driven flow, with 85–105% recovery in spiked and serum for practical identification. Post-2001 anthrax events spurred advancements in biothreat validation, with the FDA classifying detection devices as Class II to ensure standardized performance, indirectly supporting DPA biosensor development for enhanced despite ongoing research focus.

Environmental Behavior

Occurrence and Mobility

Dipicolinic acid (DPA) occurs naturally in environmental compartments primarily as a component of bacterial endospores produced by spore-forming such as those in the genera Bacillus and Clostridium, which are ubiquitous in soils, aquatic systems, and sediments. In marine sediments, DPA concentrations derived from endospore abundances range from approximately 4 to 40 µg/g dry weight, corresponding to 10⁷ to 10⁸ endospores per gram, based on a conversion factor of 2.24 fmol DPA per . Similar levels are observed in terrestrial soils, including agricultural settings where endospore-forming thrive due to and nutrient availability, with reported ranges of 10–100 µg/g in such environments reflecting higher microbial activity. The mobility of DPA in the environment is influenced by its physicochemical properties, favoring persistence in the dissolved phase. DPA is highly soluble in and exhibits low volatility, minimizing atmospheric transport and deposition. Sorption to is minimal, resulting in DPA preferentially remaining in the aqueous phase rather than binding to or minerals. DPA distribution is elevated in areas influenced by human activities, particularly near agricultural fields and industrial sites where endospore-forming or DPA-containing processes are prevalent. In agricultural soils, enhanced levels arise from natural microbial populations and potential inputs from or biopesticides like . Detection in from biotechnology processes, such as those involving production or antimicrobial applications, shows concentrations up to several ppm in treated effluents before dilution. Monitoring data indicate generally low background levels in uncontaminated environments, with concentrations typically below 1 µg/L as reported in regulatory assessments.

Biodegradation and Persistence

Dipicolinic acid (DPA), also known as 2,6-pyridinedicarboxylic acid, undergoes rapid aerobic in and aqueous environments primarily through microbial processes involving and marine . Acclimated mixed microbial cultures degrade over 80% of DPA within 12 hours at concentrations up to 1000 mg/L when provided as the sole carbon source, with no observed inhibition. This process involves initial of the ring, followed by further to open-chain intermediates. Marine , such as those grown on phthalate analogs, partially oxidize DPA to 2,3-dihydroxypicolinic acid (2,3-DHPA) as the principal under aerobic conditions. Complete mineralization to CO₂ occurs via ring cleavage, contributing to low environmental persistence. Under anaerobic conditions, DPA degradation proceeds more slowly through fermentative pathways mediated by strictly anaerobic bacteria. A defined coculture isolated from marine sediments fully degrades DPA as the sole carbon, energy, and nitrogen source, producing acetate, propionate, , and CO₂, with acetate oxidation supported by electron acceptors like fumarate or elemental . This process requires syntrophic interactions between the DPA-degrading bacterium and an acetate-oxidizing partner, indicating dependency on microbial consortia in oxygen-limited environments such as sediments. Key metabolites in aerobic degradation include hydroxylated derivatives like 2,3-DHPA, which are further broken down; in anaerobic fermentation, short-chain acids predominate. These pathways enable full mineralization without accumulation of persistent intermediates, though photolysis of 2,3-DHPA in sunlit waters ( of approximately 100 minutes at pH 8) generates additional carboxylic acids and that can assimilate. Degradation rates are influenced by microbial acclimation, with unacclimated cultures showing lags, and by environmental factors such as , where neutral to alkaline conditions (e.g., 8) facilitate both biotic and photolytic processes. DPA exhibits low persistence due to its hydrophilic nature (log Kow ≈ 0.5–0.8), preventing in organisms or soils. Ecotoxicity is minimal at environmental concentrations, with a 96-hour LC50 for exceeding 300 mg/L and no significant adverse effects predicted for aquatic life.

Applications

In Spore Detection and Biosecurity

Dipicolinic acid (DPA) serves as a primary for s, the etiological agent of , due to its abundance, comprising 5–15% of the s' dry weight in the form of calcium dipicolinate. Due to its high concentration, DPA serves as a for B. anthracis s, with targeted identification in scenarios achieved by combining DPA assays with those for B. anthracis-specific spore coat proteins via immunoassays. The in the United States accelerated the development of DPA-based detection assays, emphasizing the need for rapid, field-deployable tools to mitigate risks. These assays leverage DPA's unique properties when complexed with ions, enabling quick identification. Such technologies support in high-risk settings, including potential deployment in screening for aerosolized threats. To achieve high sensitivity—often detecting as few as 1,000 —and minimize false positives from environmental interferents or other spore-formers, DPA assays are commonly combined with multi-analyte approaches targeting B. anthracis-specific spore coat proteins via immunoassays. This dual strategy enhances specificity, ensuring accurate differentiation of . Fluorescence-based spectroscopic methods, as outlined in detection protocols, underpin these applications by providing the core mechanism for DPA sensing in operational environments.

In Materials and Biotechnology

Dipicolinic acid (DPA), an aromatic , has been investigated as a biosourced in polyesters derived from dicarboxylates, synthesized via polycondensation with diols for potential use in soil-release finishes. However, DPA-based variants exhibit limited performance in anti-redeposition and soil-release tests compared to other isomers. These polyesters generally exhibit biodegradability and non-toxicity, addressing environmental concerns associated with traditional aromatic polyesters. In , DPA functions as a in metal-organic frameworks (MOFs), contributing to structures with and sensing properties. Copper-DPA MOFs, for example, have been synthesized and cross-linked with like oxidized pectin and to form hydrogels exhibiting antibacterial activity and mechanical robustness suitable for dressings. These frameworks leverage DPA's chelating ability to coordinate metal ions, stabilizing porous architectures that facilitate selective or . Lanthanide-DPA complexes, often embedded in MOF-like coordination polymers, enable energy transfer for luminescent applications, including optical sensors. Biotechnological advancements have focused on microbial overproduction of DPA as a green chemical feedstock. Metabolic engineering of has achieved titers up to 4.7 g/L through pathway optimization, including expression of dipicolinate synthase genes and knockout of competing lysine biosynthesis routes. Similarly, engineered strains have demonstrated enhanced DPA yields up to 1.25 g/L as of 2025, supporting its use in sustainable chemical manufacturing. These efforts highlight DPA's role in circular bioeconomies by converting renewable feedstocks into value-added materials. DPA's strong with ions underpins its medical potential, particularly in agents. -DPA complexes, such as those with or , exhibit sensitized ideal for bioimaging, where DPA acts as an antenna to enhance emission in the visible and near-infrared ranges for cellular and tissue visualization. These complexes provide high signal-to-noise ratios and photostability, making them suitable for diagnostic probes. Additionally, DPA's metal-binding affinity supports applications as a chelating agent for , though clinical translation remains exploratory. As a non-toxic and readily biodegradable compound, DPA emerges as a sustainable substitute for petroleum-based dicarboxylic acids in . Its natural occurrence in bacterial spores and facile microbial production minimize environmental persistence risks, while derived materials degrade faster than fossil-fuel analogs, reducing . This positions DPA within broader efforts to develop eco-friendly aromatics for polymers and frameworks.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC1482921/
  2. https://www.chemspider.com/Chemical-Structure.9940.html
  3. https://www.chemimpex.com/products/33075
  4. https://go.drugbank.com/drugs/DB04267
  5. http://www.cmasc.gmu.edu/publications_blaisten/105.pdf
  6. https://intranet.ess.uw.edu/content/people/student_publications_files/harrold--zoe/harrold--zoe_phd_2014.pdf
  7. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1457234.htm
  8. https://biopchem.education/wp-content/uploads/2018/09/pkas_of_organic_acids_and_bases.pdf
  9. https://www.ias.ac.in/public/Volumes/jcsc/114/01/0025-0036.pdf
  10. https://europepmc.org/article/pmc/pmc1367448
  11. https://www.researchgate.net/publication/375762070_Thermal_properties_of_dipicolinic_acid_and_dipicolinic_acid_sodium_salt_NaHCOO2C5H3NH2COO2C5H3N3H2O
  12. https://digitalcommons.odu.edu/cgi/viewcontent.cgi?article=1155&context=chemistry_fac_pubs
  13. https://www.biorxiv.org/content/10.1101/803486v1.full.pdf
  14. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007015
  15. https://www.sciencedirect.com/science/article/pii/S1096717618301149
  16. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00958/full
  17. https://pubmed.ncbi.nlm.nih.gov/25402593/
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC1178406/
  19. https://pmc.ncbi.nlm.nih.gov/articles/PMC92724/
  20. https://doi.org/10.1016/j.ymben.2018.05.009
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC9024752/
  22. https://doi.org/10.1186/s12934-025-02859-x
  23. https://patents.google.com/patent/CN110229096B/en
  24. https://www.researchgate.net/publication/232844893_Controlled_Synthesis_of_2-Acetyl-6-carbethoxypyridine_and_26-Diacetylpyridine_from_26-Dimethylpyridine
  25. https://www.tandfonline.com/doi/abs/10.1080/00397919208021669
  26. https://patents.google.com/patent/CN103497152A/en
  27. https://annalsmicrobiology.biomedcentral.com/articles/10.1007/s13213-018-1361-z
  28. https://journals.asm.org/doi/10.1128/jb.184.2.584-587.2002
  29. https://www.pnas.org/doi/10.1073/pnas.0908712106
  30. https://www.researchgate.net/publication/256242668_Water_Distribution_in_Bacterial_Spores_A_Key_Factor_in_Heat_Resistance
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC99004/
  32. https://journals.asm.org/doi/10.1128/jb.182.19.5505-5512.2000
  33. https://academic.oup.com/mbe/article/36/12/2714/5539873
  34. https://journals.asm.org/doi/abs/10.1128/jb.00079-22
  35. https://pubs.acs.org/doi/10.1021/acs.chemrev.4c00615
  36. https://pubs.rsc.org/en/content/articlelanding/2015/dt/c4dt03559c
  37. https://doi.org/10.1021/ac960939w
  38. https://doi.org/10.3390/molecules29174259
  39. https://doi.org/10.1016/j.jhazmat.2016.11.030
  40. https://doi.org/10.1007/s00216-017-0836-2
  41. https://doi.org/10.1039/D3SD00314K
  42. https://doi.org/10.1007/s42114-025-01320-2
  43. https://www.fda.gov/news-events/fda-brief/fda-finalizes-requirements-help-foster-access-safe-and-effective-tests-detect-anthrax-causing
  44. https://www.science.org/doi/10.1126/sciadv.aav1024
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC8048543/
  46. https://www.atamankimya.com/sayfalar.asp?LanguageID=2&cid=3&id=13&id2=10398
  47. https://www.sigmaaldrich.com/US/en/product/aldrich/p63808
  48. https://www.fda.gov/media/155655/download
  49. https://echa.europa.eu/registration-dossier/-/registered-dossier/24614
  50. https://doi.org/10.1016/S0956-053X(98)00077-4
  51. https://doi.org/10.1128/aem.56.5.1352-1356.1990
  52. https://doi.org/10.1007/BF00117046
  53. https://foodb.ca/compounds/FDB011167
  54. https://www.fda.gov/media/79970/download
  55. https://journals.asm.org/doi/10.1128/jb.00282-07
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC10537030/
  57. https://www.sciencedirect.com/science/article/abs/pii/S0304389413001799
  58. https://www.osti.gov/servlets/purl/1335753
  59. https://pubs.acs.org/doi/10.1021/acs.accounts.1c00407
  60. https://www.sciencedirect.com/science/article/abs/pii/S0304389420328612
  61. https://doi.org/10.1021/jacsau.4c00908
  62. https://www.sciencedirect.com/science/article/abs/pii/S1096717618301149
  63. https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-025-02859-x
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