A molecular container with exceptional structure was obtained, crystallised, and examined in the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw. Resembling a rolled-up hedgehog in appearance, the molecular aggregate has a spacious cavity in its central part that can be used to transport other molecules, e.g., drugs.
Like a rolled-up hedgehog – so looks an aggregate composed of twelve calixarene molecules, obtained and examined by the researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw. They managed to crystallise the self-assembled inverted micelle-like structure which allowed them to get a deeper insight into its molecular structure at the atomic level.
Calixarenes are organic compounds with cyclic molecules composed of phenyl units. The simplest representative of the family is calixarene, consisting of four phenyl units with a cavity in the centre. The cavity is sufficiently large to host another molecule, entirely or in part, to form a molecular complex.
“In practice, we consider calixarenes as molecular analogues of chalices or baskets that can be used to transport other molecules, for instance drugs. Our group, together with colleges from the Institut de Biologie et Chimie des Protéines in Lyon, has an international patent for producing co-crystals of calixarenes with drugs”, says Dr Kinga Suwińska, associate professor at the IPC PAS.
To use calixarenes in medicine is not easy. These compounds are usually soluble only in organic solvents. Therefore, the researchers at the IPC PAS study modified calixarenes, substituted with sulphonate (-SO3H) or phosphonate (-PO3H2) groups. This way, calixarenes are converted into acidic form and become water-soluble. Tests on mice, performed two years ago by a research team from the Institut de Biologie et Chimie des Protéines, collaborating with the IPC PAS, showed that sulphonated calixarenes are not toxic in low and medium concentrations. In addition, sulphonated calixarenes show themselves biological activity, e.g., they have antiviral and antibacterial properties.
Modified calixarenes are potential drug carriers. Their importance is the higher, as the drugs, which in pure form are water-insoluble, can become water-soluble in a complex with appropriate calixarene. Furthermore, complex formation may enhance the drug’s bioavailability profile. This means that drugs – after all not always immaterial to patients’ tissues and organs – can in future be administered in lower, safer doses.
Designing appropriate complex with calixarene, researchers are able to protect complexed molecules against external factors like light or moisture. It has important practical significance. In pure form, a drug may decompose, e.g., in the upper part of the digestive tract. With calixarenes, the drug can be protected like in molecular capsule and in this form can be delivered precisely where its presence will be most desirable.
The most recent discovery of the IPC PAS’s supramolecular chemistry research group are modified calixarene molecules self-assembling into aggregates with exceptionally complex and visually appealing structure. The story began with obtaining a new calixarene derivative that crystallised as regular crystals.
“Crystalline compounds are excellent research objects. Their structure can be directly analysed using X-ray diffraction. That’s why we were able to determine so precisely, how the new calixarene molecules self-assemble”, explains Professor Suwińska.
It turns out that under certain conditions, twelve calixarene molecules assemble forming spherical structure with alcylocarbonyl groups pointing outwards. The emerging supramolecular supermolecule resembles a rolled-up hedgehog.
The picturesque supermolecule discovered in the IPC PAS is about five nanometers (billionth parts of meter) in size. Particularly important for the potential future applications is a presence of large internal void with a volume of about thousand cubic angstroms. “In the scale of the micro-world such a space is really something. Inside you can put more than 30 water molecules”, says Professor Suwińska. Due to its special structure, molecular hedgehog from the IPC PAS seems to be an ideal candidate for transporting other molecules.
Professor Suwińska makes clear that the studies conducted in the Institute of Physical Chemistry of the PAS have so far an exploratory character. Development of methods for producing such and analogous calixarene supermolecules, examination of properties of their complexes with other molecules including drugs, and testing such complexes for their possible toxicity and/or biological activity, will require long studies in collaboration with other research groups.
This press release was prepared thanks to the NOBLESSE grant under the activity “Research potential” of the 7th Framework Programme of the European Union.