1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide

changed 477207658 3-{[(Ethylimino)methylidene]amino}-N,N-dimethylpropan-1-amine EDC Structure-1.svg 210 Skeletal formula of EDC EDC molecule ball.png 240 Ball-and-stick model of the EDC molecule LMDZBCPBFSXMTL-UHFFFAOYAH correct chemspider 1S/C8H17N3/c1-4-9-8-10-6-5-7-11(2)3/h4-7H2,1-3H3 correct chemspider LMDZBCPBFSXMTL-UHFFFAOYSA-N correct CAS 1892-57-5 25952-53-8 (hydrochloride) correct CAS correct FDA RJ5OZG6I4A correct FDA 19W5TL0WJ4 (hydrochloride) 15908 correct chemspider 15119 CCN=C=NCCCN(C)C 1/C8H17N3/c1-4-9-8-10-6-5-7-11(2)3/h4-7H2,1-3H3 8 17 3 Colorless oil (freebase)White solid (hydrochloride) 112 (hydrochloride) soluble soluble in DCM, DMF, and THF External MSDS (HCl Salt) 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, EDAC or EDCI) is a water-soluble carbodiimide usually handled as the hydrochloride, which is a white solid.1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide Hydrochloride E-EROS Encyclopedia of Reagents for Organic Synthesis 2001 Richard S. Pottorf, Peter Szeto 10.1002/047084289X.re062 It is typically employed in the 4.0-6.0 pH range. It is generally used as a carboxyl activating agent for the coupling of primary amines to yield amide bonds. While other carbodiimides like dicyclohexylcarbodiimide (DCC) or diisopropylcarbodiimide (DIC) are also employed for this purpose, EDC has the advantage that the urea byproduct formed (often challenging to remove in the case of DCC or DIC) can be washed away from the amide product using dilute acid. Additionally, EDC can also be used to activate phosphate groups in order to form phosphomonoesters and phosphodiesters. Common uses for this carbodiimide include peptide synthesis, protein crosslinking to nucleic acids, but also in the preparation of immunoconjugates. EDC is often used in combination with N-hydroxysuccinimide (NHS) for the immobilisation of large biomolecules. Recent work has also used EDC to assess the structure state of uracil nucleobases in RNA.Mitchell D Renda A Douds C Babitzke P Assmann S Bevilacqua P In vivo RNA structural probing of uracil and guanine base-pairing by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) RNA 2019 25 1 147–157 10.1261/rna.067868.118 free 30341176 6298566Wang PY Sexton AN Culligan WJ Simon MD Carbodiimide reagents for the chemical probing of RNA structure in cells RNA 2019 25 1 135–146 10.1261/rna.067561.118 free 30389828 6298570 Preparation EDC is commercially available. It may be prepared by coupling ethyl isocyanate to N,N-dimethylpropane-1,3-diamine to give a urea, followed by a dehydration reaction mediated by TsCl and TEA: 10.1021/jo01351a600 1961 Sheehan, John Cruickshank, Philip Boshart, Gregory A Convenient Synthesis of Water-Soluble Carbodiimides J. Org. Chem. 26 2525 7 450px Mechanism left|thumb|440x440px|The scheme above shows the general mechanistic steps for EDC-mediated coupling of carboxylic acids and amines under acidic conditions. The tetrahedral intermediate and the aminolysis steps are not shown explicitly. EDC couples primary amines, and other nucleophiles,https://pubs.rsc.org/en/content/articlelanding/2015/np/c4np00106k 10.1039/C4NP00106K Ester coupling reactions – an enduring challenge in the chemical synthesis of bioactive natural products 2015 Tsakos Michail Schaffert Eva S. Clement Lise L. Villadsen Nikolaj L. Poulsen Thomas B. Natural Product Reports 32 4 605–632 25572105 subscription to carboxylic acids by creating an activated ester leaving group. First, the carbonyl of the acid attacks the carbodiimide of EDC, and there is a subsequent proton transfer. The primary amine then attacks the carbonyl carbon of the acid which forms a tetrahedral intermediate before collapsing and discharging the urea byproduct. The desired amide is obtained.https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/carbodiimide-crosslinker-chemistry.html Carbodiimide Crosslinker Chemistry - US www.thermofisher.com en 2019-05-10 Safety In vivo dermal sensitization studies according to OECD 429OECD https://www.oecd-ilibrary.org/environment/test-no-429-skin-sensitisation_9789264071100-en Test No. 429: Skin Sensitisation: Local Lymph Node Assay 2010 Organisation for Economic Co-operation and Development Paris en confirmed EDC is a strong skin sensitizer, showing a response at <0.01 wt% in the Local Lymph Node Assay (LLNA) placing it in Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Dermal Sensitization Category 1A.Graham Jessica C. Trejo-Martin Alejandra Chilton Martyn L. Kostal Jakub Bercu Joel Beutner Gregory L. Bruen Uma S. Dolan David G. Gomez Stephen Hillegass Jedd Nicolette John Schmitz Matthew 2022-06-20 An Evaluation of the Occupational Health Hazards of Peptide Couplers Chemical Research in Toxicology en 35 6 1011–1022 10.1021/acs.chemrestox.2c00031 0893-228X 9214767 35532537 Thermal hazard analysis by differential scanning calorimetry (DSC) shows EDC poses minimal explosion risks.Sperry Jeffrey B. Minteer Christopher J. Tao JingYa Johnson Rebecca Duzguner Remzi Hawksworth Michael Oke Samantha Richardson Paul F. Barnhart Richard Bill David R. Giusto Robert A. Weaver John D. 2018-09-21 Thermal Stability Assessment of Peptide Coupling Reagents Commonly Used in Pharmaceutical Manufacturing https://pubs.acs.org/doi/10.1021/acs.oprd.8b00193 Organic Process Research & Development en 22 9 1262–1275 10.1021/acs.oprd.8b00193 1083-6160 subscription References Further reading López-Alonso, JP Diez-Garcia, F Font, J Ribó, M Vilanova, M Scholtz, JM González, C Vottariello, F Gotte, G Libonati, M Laurents, DV Bioconjugate Chemistry 2009 10.1021/bc9001486 Carbodiimide EDC Induces Cross-Links That Stabilize RNase A C-dimer against Dissociation: EDC Adducts Can Affect Protein Net Charge, Conformation and Activity 20 1459–1473 8 19606852 Nakajima, N Ikada, Y Bioconjugate Chemistry 1995 10.1021/bc00031a015 Mechanism of Amide Formation by Carbodiimide for Bioconjugation in Aqueous Media 6 1 123–130 7711098 Category:Carbodiimides Category:Reagents for biochemistry Category:Peptide coupling reagents Category:Dimethylamino compounds