Exploiting strong, covalent bonds
for self assembly of robust nanosystems

Atomically precise self-assembly of complex structures can be engineered by providing for multiple binding interactions that

1. Cooperate to stabilize the correct configuration, in a thermodynamic sense, and
2. Do not stabilize any other configuration, in a kinetic sense

Roughly speaking, in the correct configuration, the parts fit together to allow all the binding interactions to operate simultaneously, and the system doesn’t get stuck in other configurations. It’s easy to see how weak interactions and cooperative binding can implement these conditions, but there are alternatives.

As I’ve discussed elsewhere, recent advances in biomimetic self assembly based on peptide and nucleic acid polymers provide a platform for developing complex, functional self-assembled systems, and in the right environments, some of these structures can be surprisingly robust. However, most of their characteristic binding interactions (hydrogen bonds, hydrophobic interactions, van der Waals interactions in well-packed structures, etc.) are weak in terms of both binding energy and mechanical strength.

Proteins structures, however, often include disulfide bonds (R₁–S–S–R₂), and these are covalent and strong. Their role in protein folding illustrates a key point:

Disulfide bonds can shuffle among different pairings through thiol/disulfide exchange,

a process that can be fast in the presence of R–S^– ions. A well-folded structure will strongly favor correct pairings by holding a momentarily displaced R–S^– in a position to reform the bond. In thermodynamic terms, this decreases the entropy cost of the bond-forming reaction, and in kinetic terms, it increases the effective concentration that drives the forward reaction, typically accelerating it by an large factor (> 10³). Exchange can be shut off by decreasing pH or removing free thiols from the folding environment.

The formation and hydrolysis of boronate esters can play a similar role in artificial self-assembling systems. A sample chapter from Boronic Acids (2005, posted by Wiley-VCH Verlag) provides an extensive discussion of the chemistry of boronic acid derivatives; it notes that boronic acids (at high pH, as hydroxyboronate anions) react with diols to form boronate esters with forward rate constants in the 10³ – 10⁴ M ^–1s^–1 range. Hydrolysis is likewise fast. Boronate esters can be stabilized by reducing pH or removing water. They, and boronic acids, are generally biocompatible, and have even been developed as drugs, where they serve to bind carbohydrate moieties.

Here are some recent papers on self assembled systems that discuss boronic acid chemistry, along with other covalent chemistries of similar utility:

• “An Iminoboronate Construction Set for Subcomponent Self-Assembly”
• “Complex Systems from Simple Building Blocks via Subcomponent Self-Assembly”

And a dissertation:

• “Self-Assembly of Boron-Based Supramolecular Structures” [pdf]

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Self assembly need not be biomimetic.

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See also:

• Effective Concentration in Self Assembly,
  Catalysis, and Mechanosynthesis (1)
• Effective Concentration in Self Assembly,
  Catalysis, and Mechanosynthesis (2)
• Self-assembling nanostructures: Building the building blocks

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Tagged as: chemistry, self assembly