Self-assembly for biological systems

In biological systems, there are many examples of self-assembly, just think of spontaneous reversible DNA double helix starting from two strands complementary to deoxyribonucleic acid. Other examples are found in the formation of cell membranes, multi-component enzymes, and viruses. In this way, nature exploits a limited number of often simple interactions between molecules to produce very structures complex. A striking example is that of the tobacco; this virus is made up of 2130 subunits of a protein and a strand of RNA. Proteins self-assemble around the RNA strand via non-covalent interactions to form the superstructure of the virus.

Self-assembly opens the way to new molecular structures that would be inaccessible, or accessible only in very low yields, through the traditional techniques of formation and breaking of covalent bonds. The new ones "Molecular buildings" are generated by combining sub-units properly designed; they can also be very simple, and yet they can generate in following the assembly of very complex architectures. 

These self-assembled supra-molecules can have many potential applications, ranging from information storage (computer molecules) to drug delivery. The self-assembly technique exploits the whole set of non-covalent chemical interactions already widely examined, such as van der Waals forces, hydrogen and non-hydrogen bonds, and coordination links. Of course, given the type of synthetic approach, they will be preferred those interactions that are highly directional, such as hydrogen bonds and those of coordination (which are also considerably stronger).

In principle, this synthetic approach has a number of advantages over the classic one covalent synthesis, which, against a considerable commitment in terms of synthesis and purification of products, often has not high selectivity and, therefore, low yields. Self-assembly is a process highly convergent and therefore requires a much lower number of passes than the corresponding covalent synthesis; in this case, the synthetic effort is limited to the construction of relatively small building blocks. Also, since non-covalent interactions usually occur very quickly, the formation of the final product is fast. Finally, if the self-assembly process is reversible (usually non-covalent interactions are labile), then the desired supra-molecule is also the thermodynamic product of the reaction. 

The process can be, in principle, "defect-free" since any by-products deriving from incorrect self-assembly convert spontaneously, through the fast balance, into the product thermodynamic (the synthesis is also said to be self-healing). Ultimately, the self-assembly method allows a process of formation of the supra-molecule, usually more selective (if the design of the building blocks is correct) with higher yields and more purification procedures simple.

On the other hand, supra-molecules are often less stable, both thermodynamically and kinetic, compared to covalent "molecular buildings." Typically, although stable from the point of view thermodynamic because comprising multiple interactions, the supra-molecules are in balance dynamic with components.

Self-assembly and coordination links

It can be said that in the last decade, the synthesis strategy that involves the use of transition and coordination links in the formation of supra-molecular adducts through self-assembly. It has become increasingly important and has emerged as an alternative concrete to the formation of aggregates through hydrogen bonds, deriving from macromolecules natural. In principle, this synthetic approach, in addition to the numerous advantages of self-assembly compared to the classic covalent approach already described above, presents others:

• A topological (or geometric) advantage, since the coordination compounds, allows the introduction into the system of bond angles difficult to obtain in chemistry classic organic, especially 90 ° angles. Depending on the nature of the metal and it's around coordinative. It is possible to choose not only the geometry of the complex (e.g., linear, planar square, tetrahedral, octahedral) but also the number and geometry of the labile sites to engage in the construction of the supra-molecule.

• In the context of non-covalent interactions, coordination links are definitely the most strong; the bond strength can vary in a range from 15 to 30 kcal/mol (i.e., intermediate between the strong covalent bonds of the classic macrocycles and the weak interactions typical of the biological systems). Supra-molecular adducts obtained in this way will, therefore, generally stable enough to be isolated and treated like any discrete molecule.

Furthermore, depending on the nature of the metal and its oxidation state, it is possible to choose between inert and labile bonds (e.g., Pd (II) labile vs. Pt (II) inert) or switch from one situation to another varying the oxidation state of the metal (e.g., Co (II) labile vs. Co (III) inert):

• The metal center can introduce redox and /or properties into the supra-molecular system photochemical

Transition metals, given their electronic characteristics, can obviously come considered as accepting subunits, that is, to be considered acid building blocks (intended as Lewis acids). They can be connected through appropriate basic building blocks (intended as Lewis bases), i.e., containing peripheral donor atoms (e.g., heterocyclic or nitrogen ligands aromatic binders replaced with cyan groups), to form the supramolecular structure. Both building block types must have specific geometries, that is, be sufficiently rigid and be multi identified or, at least, bidentate (i.e., they must not be terminal building blocks, i.e., with one binding site).

From a purely geometric point of view, building blocks, both acidic and basic, can come classified according to the number of coordination sites and their relative geometry. 

Thus a linear building block will have 180 ° reactive sites, while angular units will have sites arranged at angles less than 180 °. When acid and basic building blocks of this type come combined, the structure of the resulting species will depend only on symmetry and the number of sites of the bond of each sub-unit. 

 For example, the assembly of an equilateral molecular triangle requires the combination of three linear and three corner building blocks with 60 ° angles.

A molecular square can be obtained in different ways, or by combining four linear units with four 90 ° angular units (4 + 4 squares), or by combining two different 90 ° corner units (2 + 2 squares). The construction of polyhedral systems (3D) is more complex, as it requires the self-assembly of a much greater number of units. Moreover, usually at least one of the building blocks must possess at least three non-coplanar coordination sites. For example, for the construction of a cube are 12 linear units and 8 tridentating units with 90 ° angles required. However, that, as three-dimensional structures can also be obtained from the assembly of planar or relatively flexible fragments. It is important to stress that in this approach we generally assume that building blocks are rigid, that is, that the angles between the coordination sites in the units do not change significantly in followed by self-assembly.

Author: Vicki Lezama