Spreading or pinning of a liquid drop on a solid substrate is determined by the surface energy of solid and liquid, topography of substrate surface, and different external forces like electric field, magnetic field, and vibration. Here we present a novel mechanism of depinning, driven by in situ generation of a species following reaction between a constituent of the droplet and one in the substrate. In particular, fluoro-carbon (FC) functionalized agarose and pHEMA gels are used as the substrates; the substrate is soaked with chloroauric acid. A drop of poly(dimethylsiloxane) (PDMS) mixed with the cross-linking agent is dispensed on it. The drop does not spread in absence of the salt, but as the salt concentration increases, the spreading diameter increases with decrease in the contact angle. The Si-H group, present as a constituent in the cross-linking agent, reduces the salt, leading to in situ generation of gold nanoparticles, that mitigates the pinning effect of the drop and the drop spreads.