title: Different EDC/NHS activation mechanisms between PAA and PMAA brushes and the following amidation reactions.
abstract: Infrared spectroscopy was applied to investigate the well-known EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) activation details of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) brushes grafted on porous silicon. Succinimidyl ester (NHS-ester) is generally believed to be the dominant intermediate product, conveniently used to immobilize biomolecules containing free primary amino groups via amide linkage. To our surprise, the infrared spectral details revealed that the EDC/NHS activation of PMAA generated anhydride (estimated at around 76% yield and 70% composition), but not NHS-ester (around 5% yield and 11% composition) under the well-documented reaction conditions, as the predominant intermediate product. In contrast, EDC/NHS activation of PAA still follows the general rule, i.e., the expected NHS-ester is the dominant intermediate product (around 45% yield and 57% composition), anhydride the side product (40% yield and 28% composition), under the optimum reaction conditions. The following amidation on PAA-based NHS-esters with a model amine-containing compound, L-leucine methyl ester, generated approximately 70% amides and 30% carboxylates. In contrast, amidation of PAA- or PMAA-based anhydrides with L-leucine methyl ester only produced less than 30% amides but more than 70% carboxylates. The above reaction yields and percentage compositions were estimated by fitting the carbonyl stretching region with 5 possible species, NHS-ester, anhydride, N-acylurea, unreacted acid, unhydrolyzed tert-butyl ester, and using the Beer-Lambert law. The different surface chemistry mechanisms will bring significant effects on the performance of surface chemistry-derived devices such as biochips, biosensors, and biomaterials.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, Jiangsu, China.
authors.forename: Cuie
authors.initials: C
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Liu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhou
authors.forename: Shou-Jun
authors.initials: SJ
authors.lastname: Xiao
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D002234:Carbodiimides / Q000737:chemistry*; D004123:Dimethylamines / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D002234:Carbodiimides; D004123:Dimethylamines; C569266:N-ethyl-N'-(3-(dimethylamino)-propyl)carbodiimide; D011109:Polymethacrylic Acids; D013388:Succinimides; C030613:polymethacrylic acid; C006903:carbopol 940; C001426:N-hydroxysuccinimide; D012825:Silicon