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Synonyms: 2,2'-Bipyridine-5,5'-dicarboxylic Acid; PD 086195; 5,5'-Dicarboxy-2,2'-bipyridine

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Umar, Sheriff ; Catazaro, Jonathan ; Wachira, James ; Samokhvalov, Alexander ;

Abstract: Gemcitabine is a powerful anticancer antimetabolite drug which is usually administered as hydrochloride salt (GemHCl), but its systemic administration is accompanied by the undesirable “burst” phenomenon and its adverse side effects. To avoid the “burst”, drugs can be encapsulated on suitable matrices to yield a local and delayed release. Here, GemHCl was encapsulated on aluminum metal-organic framework MOF-253 by liquid-assisted grinding (LAG) to form a new pharmaceutical composite. In the composite, the bonding was determined by the complementary ATR-FTIR spectroscopy, solid-state NMR (SS-NMR) spectroscopy and powder XRD. The interactions “drug-matrix” proceed by the C−N group of GemHCl drug and the bipyridyl unit of linker in MOF-253 matrix. Next, a powder of the composite was processed to obtain a mechanically pressed robust pharmaceutical pellet. The pellet was further tested for the in-vitro delayed release of gemcitabine to phosphate buffered saline (PBS) at 37 °C using an automated drug dissolution system (ADDS). The pellet of the composite is found to be stable in PBS, and it shows delayed drug release up to 5 days without the “burst”, in contrast to the pellet of GemHCl which quickly dissolves. Next, in the in-vitro viability tests of pancreatic cancer cells PANC−1 by the Alamar Blue fluorescence assay in the 72 h. timescale, the composite is found to be more toxic than GemHCl. Finally, the prolonged toxicity of the released gemcitabine to PANC−1 cells was investigated by continuous measurements of proliferation (growth) for 6 days, using xCELLigence Real Time Cell Analyzer (RTCA). At higher concentrations and longer times, the composite is more effective than pure GemHCl, consistently with delayed drug release from the former. The encapsulation of GemHCl on MOFs by the means of mechano-chemistry constitutes a new and promising approach for the preparation of advanced functional composites for controlled, delayed and local drug release, and their potential use in the anticancer drug-eluting implants.

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Product Details of 2,2'-Bipyridine-5,5'-dicarboxylic acid

CAS No. :1802-30-8
Formula : C12H8N2O4
M.W : 244.20
SMILES Code : C1=CC(=CN=C1C2=NC=C(C=C2)C(O)=O)C(O)=O
Synonyms :
2,2'-Bipyridine-5,5'-dicarboxylic Acid; PD 086195; 5,5'-Dicarboxy-2,2'-bipyridine
MDL No. :MFCD01318320
InChI Key :KVQMUHHSWICEIH-UHFFFAOYSA-N
Pubchem ID :192744

Safety of 2,2'-Bipyridine-5,5'-dicarboxylic acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 2,2'-Bipyridine-5,5'-dicarboxylic acid

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 1802-30-8 ]

[ 1802-30-8 ] Synthesis Path-Upstream   1~3

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YieldReaction ConditionsOperation in experiment
77% at 0℃; for 24 h; Reflux Diethyl 2,2'-bipyridine-5,5'-dicarboxylate
Procedure:
Bipy55'DC (200 mg, 0.82 mmoles) and EtOH (13 mL) were added to a dried flask and stirred on ice.
Thionyl chloride (1.3 mL) was added dropwise on ice, after which the flask was fitted with a reflux condenser and heated at reflux.
After 24 hr, the reaction was cooled on ice and quenched by the dropwise addition of saturated Na2CO3 (20 mL).
The aqueous layer was extracted with CH2Cl2 (4*20 mL) and the combined organics were dried over Na2SO4(s), and concentrated under reduced pressure.
The crude product was then purified by chromatography on silica (3percent acetone in 1:1 DCM/hexanes) to afford the title compound (190 mg, 77percent) as a white solid. 1H NMR (500 MHz, CDCl3) δ 9.32 (dd, J=0.5, 2.0 Hz, 1H), 8.59 (dd, J=0.5, 8.5 Hz, 1H), 8.46 (dd, J=2.0, 8.5 Hz, 1H), 4.47 (q, J=7.5 Hz, 2H), 1.46 (t, J=7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 165.2, 158.3, 150.6, 138.1, 126.6, 121.3, 61.6, 14.3; HRMS (ESI) m/z 301.1193 [calc'd for C16H17N2O4 (M+H)+ 301.1183].
References: [1] Inorganic Chemistry, 2017, vol. 56, # 3, p. 1366 - 1374.
[2] Chemistry - A European Journal, 2012, vol. 18, # 23, p. 7030 - 7035.
[3] Dalton Transactions, 2016, vol. 45, # 3, p. 881 - 885.
[4] Chemical Communications, 2016, vol. 52, # 48, p. 7600 - 7603.
[5] Journal of the American Chemical Society, 2017, vol. 139, # 49, p. 17747 - 17750.
[6] Chemistry - A European Journal, 2018, vol. 24, # 10, p. 2457 - 2465.
[7] Chemistry - A European Journal, 2018, .
[8] Patent: US2016/280701, 2016, A1, . Location in patent: Paragraph 0300; 0301; 0302.
[9] Journal of the American Chemical Society, 2012, vol. 134, # 2, p. 968 - 978.
[10] Journal of Molecular Catalysis A: Chemical, 2010, vol. 331, # 1-2, p. 117 - 124.
[11] European Journal of Inorganic Chemistry, 1999, # 9, p. 1507 - 1521.
[12] Chemical Communications, 2009, # 41, p. 6237 - 6239.
[13] Journal of Heterocyclic Chemistry, 1977, vol. 14, p. 191,193.
[14] Journal of the American Chemical Society, 1982, vol. 104, # 26, p. 7519 - 7526.
[15] Dalton Transactions, 2008, # 28, p. 3701 - 3708.
[16] Physical Chemistry Chemical Physics, 2014, vol. 16, # 28, p. 14874 - 14881.
[17] Patent: CN106496113, 2017, A, . Location in patent: Paragraph 0059; 0060; 0066; 0067; 0073; 0074.
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References: [1] Chemistry - A European Journal, 2013, vol. 19, # 40, p. 13369 - 13375.
  • 3
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References: [1] Journal of Medicinal Chemistry, 1993, vol. 36, # 24, p. 3853 - 3858.
[2] Journal of Medicinal Chemistry, 1993, vol. 36, # 24, p. 3853 - 3858.
 

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