Supramolecular Homogeneous Organic Transformations (SHOT)

Our research group has a long tradition of collaborations with pharmaceutical and chemical industries for the optimization of the synthetic methods for the preparation and isolation of API and drug candidates. Moreover the group has been involved for years in the development of new bisphosphonates as potential drug candidates for the treatment of bone resorption disorders, like osteoporosis and Paget disease. Recent applications of bisphosphonates by the group span from the development of new anionic surfactants to the functionalization of metal oxide nanoparticles to impart specific surface properties.

Among pigments, diketopyrrolepyrrole (DPP) represents one of the most interesting and investigated organic units in virtue of its excellent durability, high stability. Our research starts from DPP, implementing the scaffold of the pigment with other specific functionalities in order to impart different aggregation properties in a wide range of solvents, from the apolar hexane to water. The aim is to create a self-healing pigment, whose color and aggregation properties can be tuned and reversibly modified to afford new auto-repairing and shaded colors. Moreover, the modification of typical commercial polymers based on H-bonded poly-oxazoline units, like AquazoleTM, will enable the formation of self-repairing ligand, that will facilitate the future restoration thanks to the reversibility of the cross-linking of the polymeric structure where the typical pigments are dispersed.

“Natural BioZipper” is a project aimed at the implementation of natural biopolymers, in particolar polysaccarides such as ialuronic acid and chitosane, via reversibile supramolecular interactions, in order to prepare hydrogels with a high water loading capacity to be implemented for regenerative medicine, bio-sensors or as drug delivery systems. The core of the project is the functionalization of such biopolymers with chemical units that upon request can undergo reversible cross-linking between the chains, under the presence of external stimuli like heat, light or pH changes. Examples are the use of photo-dimerizable or H-bonding dimerizable units, covalently connected to the biopolymers allowing the reversible process thanks to the use of a specific light wavelenght or the switch of pH.

Our research group has been studying the synthesis and the applications of syn-benzocyclotrimers, which offer a possible alternative to other highly symmetric scaffolds. These cup-shaped molecules are built around an aromatic central nucleus. At variance with calixarenes, they are quite more rigid, although they are tunable in shape, size and electronic properties. A number of original methodologies aimed to the synthesis of these molecules have been disclosed with high syn to anti diastereoselectivity, to finally invert the expected statistical 1:3 ratio. The possibility of obtaining good yields in widely functionalized benzocyclotrimers and in a good syn diastereoselectivity made possible the study of supramolecular applications. Properly functionalized benzocyclotrimers featuring complementary size and shape with the guest counterpart were proved to include molecules such as fullerene, water, ammonium ions. Even more significant is the detection of capsules that spontaneously forms in solution in the presence of various gases (argon, methane, oxygen, nitrogen, carbon monoxide). Alternatively, cage-like molecules were obtained, which were able to host small molecules (methane, acetylene, ethylene, ethane). 

Solvents represents much more than half of the mass of chemical transformations, therefore in order to minimize the impact of this on the environ, it is highly desirable to move to more environmentally friendly solvents. Water is the solvent that Nature selected for all chemical transformations under mild conditions but this is contrasted by the typical low solubility of organic reagents in water.
Mimicking Nature, it is possible to exploit the potentialities of water running reaction under “on water” or “in water” or in the presence of micellar media as nanoreactors to have a better control of the product selectivity at all level, with the possible advantages of easy product isolation and in some cases suitable catalyst recycling.
Our research group largely demonstrated that micellar systems provide large advantages in terms of reactivity, product selectivity from chemo, regio and often enantioselectivity as well as substrate selectivity for a wide range of metal catalyzed reactions (hydroformylations, oxidation and other C-C and C-X bond forming reactions).

In homogeneous catalysis still a large gap of knowledge lies in between man-made homogeneous catalysts and Nature-made enzymes. This gap will be crossed only implementing elements of supramolecular chemistry, molecular recognition and molecular dynamic processes into the homogeneous catalysts of tomorrow. A cross-contamination between supramolecular chemistry and homogeneous catalysis is crucial to tackle this ambitious target.
The development of nanoreactors and molecular vessels for catalytic applications is the new frontier of enzyme mimics and our group has been involved for years in the application of hydrogen bonded capsule in catalysis like the hexamer of resorcin[4]arene. The latter capsule demonstrated to act as: i) a nanoreactor imparting substrate and product selectivity to reactions; ii) a reversible inhibitor to modulate the activity of a metal catalyst and iii) as a supramolecular organocatalyst that binds specific substrates as well as electron poor intermediates and accelerates the rate of reaction with features that are typical of enzymes.