Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC₅₀ values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.

Poly(ethylene glycol) (PEG) is the standard stealth polymer to functionalize lipid nanoparticle (LNP) surfaces, requiring conjugation to a lipid tail for anchoring in the LNP’s shell. We eliminate the need for lipid conjugates by introducing a new polymer-only design principle using function-encoded statistical polymers. For that, we synthesized statistical amphiphilic copolymers in which hydrophobic units are followed by hydrophilic units, with the intention that the hydrophobic units of the polymer anchor to the LNP surface, and its hydrophilic parts stealth the particle surface. We screened the formulation space using a 42-member poly(2-oxazoline) library, yielding design rules for successful LNP formulations. Cryogenic transmission electron microscopy confirmed the intact LNP structure, and biological activity was assessed in multiple human cell types differentiated from inducible pluripotent stem cells. Intravenously administered barcoded LNPs formulated with function-encoded statistical polymers compared to the equivalent PEG-lipid LNPs showed 2.5- and 5-fold higher amounts in mice and lower bloodstream levels, leading to significantly higher accumulation in the spleen and liver. Rather than assembling LNP interfaces from multiple molecular components, this work establishes that orthogonal interfacial functions can be encoded directly into the architecture of a single statistical polymer, providing a general molecular design principle for programmable nanomedicine interfaces.