Synthesis of Lipophilic Guanine N-9 Derivatives: Membrane Anchoring of Nucleobases Tailored to Fatty Acid Vesicles.

Covalent or noncovalent surface functionalization of soft-matter structures is an important tool for tailoring their function and stability. Functionalized surfaces and nanoparticles have found numerous applications in drug delivery and diagnostics, and new functionalization chemistry is continuously being developed in the discipline of bottom-up systems chemistry. The association of polar functional molecules, e.g., molecular recognition agents, with soft-matter structures can be achieved by derivatization with alkyl chains, allowing noncovalent anchoring into amphiphilic membranes. We report the synthesis of five new guanine-N9 derivatives bearing alkyl chains with different attachment chemistries, exploiting a synthesis pathway that allows a flexible choice of hydrophobic anchor moiety. In this study, these guanine derivatives were functionalized with C10 chains for insertion into decanoic acid bilayer structures, in which both alkyl chain length and attachment chemistry determined their interaction with the membrane. Incubation of these guanine conjugates, as solids, with a decanoic acid vesicle suspension, showed that ether- and triazole-linked C10 anchors yielded an increased partitioning of the guanine derivative into the membranous phase compared to directly N-9-linked saturated alkyl anchors. Decanoic acid vesicle membranes could be loaded with up to 5.5 mol % guanine derivative, a 6-fold increase over previous limits. Thus, anchor chemistries exhibiting favorable interactions with a bilayer's hydrophilic surface can significantly increase the degree of structure functionalization.

Emergent Properties of Giant Vesicles Formed by a Polymerization-Induced Self-Assembly (PISA) Reaction.

Giant micrometer sized vesicles are of obvious interest to the natural sciences as well as engineering, having potential application in fields ranging from drug delivery to synthetic biology. Their formation often requires elaborate experimental techniques and attempts to obtain giant vesicles from chemical media in a one-pot fashion have so far led to much smaller nanoscale structures. Here we show that a tailored medium undergoing controlled radical polymerization is capable of forming giant polymer vesicles. Using a protocol which allows for an aqueous reaction under mild conditions, we observe the macroscale consequences of amphiphilic polymer synthesis and the resulting molecular self-assembly using fluorescence microscopy. The polymerization process is photoinitiated by blue light granting complete control of the reaction, including on the microscope stage. The self-assembly process leads to giant vesicles with radii larger than 10 microns, exhibiting several emergent properties, including periodic growth and collapse as well as phototaxis.

Interactions between catalysts and amphiphilic structures and their implications for a protocell model.

One of the essential elements of any cell, including primitive ancestors, is a structural component that protects and confines the metabolism and genes while allowing access to essential nutrients. For the targeted protocell model, bilayers of decanoic acid, a single-chain fatty acid amphiphile, are used as the container. These bilayers interact with a ruthenium-nucleobase complex, the metabolic complex, to convert amphiphile precursors into more amphiphiles. These interactions are dependent on non-covalent bonding. The initial rate of conversion of an oily precursor molecule into fatty acid was examined as a function of these interactions. It is shown that the precursor molecule associates strongly with decanoic acid structures. This results in a high dependence of conversion rates on the interaction of the catalyst with the self-assembled structures. The observed rate logically increases when a tight interaction between catalyst complex and container exists. A strong association between the metabolic complex and the container was achieved by bonding a sufficiently long hydrocarbon tail to the complex. Surprisingly, the rate enhancement was nearly as strong when the ruthenium and nucleobase elements of the complex were each given their own hydrocarbon tail and existed as separate molecules, as when the two elements were covalently bonded to each other and the resulting molecule was given a hydrocarbon tail. These results provide insights into the possibilities and constraints of such a reaction system in relation to building the ultimate protocell.