This paper reports novel findings of a study of interfacial chemical derivatization reactivities at the interconnecting linkages of core-shell nanoparticle network films. Starting from thin film assemblies of gold nanoparticles linked by head-to-head hydrogen-bonded carboxylic acid terminals, we have demonstrated the conversion of the hydrogen-bonded linkages to anhydride linkages via dehydration reaction. The anhydride was further shown to serve as a new platform for immobilizing amine-functionalized molecular species. We present infrared reflection spectroscopic data to characterize the interfacial structures derived from each of these interfacial reactivities. The unique symmetric and asymmetric stretching bands of the anhydride groups allowed facial identification and assessment of the interfacial reactivities. The potential application of the derivatization, strategy for immobilizing biological molecules onto the derivatized nanoparticle assemblies was also explored.