FTIR-ATR spectroscopy for monitoring polyanhydride/anhydride-amine reactions

J Control Release. 2000 Nov 3;69(2):273-81. doi: 10.1016/s0168-3659(00)00312-6.

Abstract

The reactivity of 1,3-bis(p-carboxyphenoxy) propane:sebacic acid anhydride copolymer (CPPSA1:6), myristic and benzoic anhydrides with amine nucleophiles were investigated in non-polar solvents. FTIR-ATR (attenuated total reflectance) spectroscopy was used to monitor the polyanhydride/anhydride reaction rates in dichloromethane, dichloroethane, chloroform, and 1,4-dioxane solutions at room temperature. The reaction kinetics was determined by measuring the anhydride peak loss with time. Aminolysis resulted from nucleophilic attack of the added amine on the carbonyl group of the anhydride moiety. Primary and secondary amines reacted to form amides and the reaction followed second-order kinetics. Second-order rate constants and reaction half-life (t(1/2)) were calculated from the semilog plots of [anhydride]/[amine] in 1,4-dioxane at room temperature. The aminolysis rate decreased with pK(a) of the amine reactant, and half-life (t(1/2)) decreased with increasing amine concentration, as expected. With trifluoroethylamine (pK(a) 5.8), myristic anhydride reacted about 6-fold faster than benzoic anhydride. The lower reaction rate of benzoic anhydride was due to the higher stability of the aromatic anhydride compared to aliphatic. The overall CPPSA1:6 copolymer reactivity was the sum of aliphatic-aliphatic (SA-SA), aliphatic-aromatic (SA-CPP), and aromatic-aromatic (CPP-CPP) anhydride linkage reactivities. Based on the monomer ratio, the probability of SA-SA, SA-CPP, and CPP-CPP dyads were calculated to be 0.74, 0.24, and 0.02, respectively. This indicated that CPPSA1:6 reactivity will mainly result from SA-SA and SA-CPP linkages. The second-order rate constants and t(1/2) obtained for CPPSA1:6 with TFEA were closer to those for myristic anhydride than benzoic anhydride with TFEA.

MeSH terms

  • Algorithms
  • Amines / chemistry*
  • Anhydrides / chemistry*
  • Benzoates / chemistry
  • Decanoic Acids / chemistry*
  • Differential Thermal Analysis
  • Half-Life
  • Kinetics
  • Myristic Acid / chemistry
  • Polyesters / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Amines
  • Anhydrides
  • Benzoates
  • Decanoic Acids
  • Polyesters
  • Myristic Acid
  • decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer