There are several molecular level mechanisms at the origin of biological functions that serve as inspiration for the development of the “next generation” of materials that display adaptive and interactive properties. However, it will take time for synthetic materials to approach the level of complexity, robustness, and adaptability of biological systems. Although there are switchable platforms that respond via sensitized molecular components, there are currently no examples of materials that truly possess the type of autonomous behavior seen in biological systems. Even though these concepts are common in living organisms, their translation into a synthetic platform remains challenging to this day. The development of such systems requires the unraveling of the structural and energetic bases that underlie autonomous processes at the molecular level, and this work focuses on fundamentally understanding some of these concepts. By bringing about covalent and non-covalent transformations at the interface of supramolecular assemblies, we have investigated how these modifications can cause systemic energy changes, which in turn dictates overall outcome of these interfacial modifications. An insight into these processes would support the future development of supramolecular platforms that display autonomous behavior.