Our work deals with the preparation of complex structures using a process we refer to as subcomponent self-assembly. In this process, simple building blocks (generally aldehydes and amines) come together around templates, which are often metal ions like copper(I) and iron(II), although boron may be used as well. Both covalent (generally C=N) and coordinative (N→Template) bonds are formed during the same overall self-assembly process. Although a great range of products may be possible in theory-and the system may "sample" many different structures during thermodynamic equilibration, only a small subset of all possible product structures are stable with respect to the others.
Our central challenge is thus to figure out the rules governing which product structures may be expected to emerge from a complex self-assembling system. These rules may then be used synthetically, to create complex and potentially functional assemblies.
Our past work has investigated a number of different systems. A few highlights are given below.
The Cu4 grid shown below is strained, an unusual feature for self-assembled structures. The observation that it only formed in water, among all the solvents tried, led is to conclude that the hydrophobic effect was stabilising this compact structure, effectively counterbalancing the strain.
"The hydrophobic effect as a driving force in the self-assembly of a [2 x 2] copper(I) grid" J.R. Nitschke*, M. Hutin, and G. Bernardinelli Angew. Chem. Int. Ed. 2004, 43, 6724-6727.
Understanding the rules governing iminoboronate ester formation allowed us to prepare the cagelike structure shown below.
"An iminoboronate construction set for subcomponent self-assembly" M. Hutin, G. Bernardinelli, and J.R. Nitschke* Chem. Eur. J., 2008, in press.
The two mononuclear complexes shown at left below do not exchange ligands with each other. Adding phenylenediammonium, however, induces a covalent exchange process based upon pKA differences. Proton transfer from the more acidic (aromatic) amine to the less acidic (aliphatic) amine residue results in the latter's ejection from its copper(I) complex, freeing the deprotonated aromatic amine to incorporate in its place. The aromatic-amine-containing copper complex then undergoes ligand exchange with the bis-isoquinoline copper(I) complex shown, yielding the heteroleptic complex shown at right.
This sequence of reactions forms a new kind of cascade reaction, wherein a covalent rearrangement triggers a coordinative exchange.
"Dynamic covalent and supramolecular direction of the synthesis and reassembly of copper(I) complexes" D. Schultz and J.R. Nitschke* Proc. Natl. Acad. Sci. USA 2005, 102, 11191-11195.
One of our studies revealed that the displacement of one aniline for another within copper(I) complexes was strongly influenced by electronic effects, and that these effects could be quantified using the Hammett Equation. This allowed us to design reaction sequences in which one amine sequentially displaced another in high yield, as shown below.
"Designing multistep transformations using the Hammett equation: Imine exchange on a copper(I) template" D. Schultz and J.R. Nitschke* J. Am. Chem. Soc., 2006, 128, 9887-9892.
The pair of aldehydes and amines shown below in aqueous solution gives a complex dynamic combinatorial library of potential ligands, all in equilibrium with each other and the starting materials. Addition of copper(I) and iron(II) to this library results in the elimination of all but two of these library members during the formation of the two product structures shown at right. The coordination preferences of the metal ions drive this sorting process to completion.
"Choices of iron and copper: cooperative selection during self-assembly" D. Schultz and J.R. Nitschke* Angew. Chem. Int. Ed. 2006, 45, 2453-2456.
When racemic 3-aminopropane-1,2-diol was used as a subcomponent to make the dicopper helicate shown below, NMR spectra indicated the formation of a complex mixture of diastereomers: the reaction appeared to proceed without diastereoselectivity. Upon crystallisation, however, this set of diastereomers was observed to rearrange, via exchange at the structures' coordinative and dynamic-covalent imine linkages, to give only a single pair of enantiomers. When the crystals were re-dissolved, the original mixture of diastereomers was observed to regenerate: this mixture thus makes up a dynamic combinatorial library that can be sorted through crystallisation.
"Self-sorting subcomponent rearrangement during crystallization" M. Hutin, C.J. Cramer, L. Gagliardi, A.R.M. Shahi, G. Bernardinelli, R. Cerny, and J.R. Nitschke* J. Am. Chem. Soc., 2007, 129, 8774-8780. Highlighted in the News & Views article "Molecular socks in a drawer" by M.D. Ward, Nature 2007, 449, 149-150.