Description of the doctoral training

1. Detailed description of the scientific and technological significance of the doctoral training

General

Supramolecular association and organization of matter is a key feature that allows construction of objects with specific functions or materials with defined properties. Most interesting, useful and desired properties are obtained when the organization of matter occurs at a microscopic or even nanoscopic level. Order at such small length scales can only be obtained by self-organization of macromolecules, usually driven by thermodynamic interactions. As examples of usefulness of such organization we can mention polymers associated in forms of micelles that can be made to enclose in their center some desirable substance which then is protected and possibly carried to a designed place. From a different perspective, micelle formation and microphase separation of bulk block copolymers made of hard and soft blocks leads to materials with remarkable properties.

Although organized supramolecular structures occur and can be generated in most diverse polymers with completely different aims and applications, the driving force for the organization is always a more or less strong incompatibility between different parts of the macromolecule and between the macromolecule and its environment. In the same way, common experimental techniques are used to characterize the supramolecular structure of polymers designed for very different applications.

The proposed doctoral training aims at giving to hosted fellows a theoretical background as well as practical experience with designing, producing, controlling and characterizing ordered supramolecular polymer materials that can be used in biological environments or as materials with technological significance. Members of the Training Site can offer expertise in the fields schematically described below, but it is understood that the exact program for a hosted fellow will be tailored, in cooperation with his home laboratory, according to the subject of his ongoing PhD studies and according to the requested length of stay at the Training Site.

Biologically active molecules

In the field of the study of molecular and supramolecular polymer systems designed as carriers of biologically active molecules this project offers two topics in which PhD students can obtain training and education: (i) study of conjugates of synthetic and natural macromolecules as targetable drug carriers and (ii) development of self-assembled complexes of polycations with DNA and plasmids as gene delivery systems.

Synthesis of water-soluble reactive polymers and their conjugation with drugs and biologically active proteins or glycoproteins (antibodies) result in development of polymer drugs facilitating site-specific therapy. The research group at IMC is experienced in designing, synthesis and detailed study of the tumour and tumour cell-specific polymer-based anticancer drugs. Students can obtain training in the synthesis of monomers, peptides and drug derivatives, synthesis of hydrophilic polymers, methods of conjugation of synthetic polymers with biologically active proteins and design and physico-chemical and biological characterization of effective antibody-targeted polymer drugs.

Self-assembly of polycations, or their block and graft copolymers with hydrophilic polymers, with DNA or specific plasmids results in nanoparticulate systems. Such systems, after surface modification with synthetic polymers, fusogenic molecules or specific bioadhesive proteins are being developed as efficient vectors for gene therapy. The project offers the students training also in this exciting and new interdisciplinary research including synthesis of monomers, block and graft polymers, self-assembly processes with DNA, particle modifications with hydrophilic polymers and biologically active molecules as well as purification methods and physico-chemical characterisation of the nanoparticulate systems.

Biodegradable Polymers

The students can also learn about the synthesis of biodegradable polymers and the studies of their properties as biomaterials. They will get experience in the living ring-opening polymerisations of lactones, such as lactides, glycolide and/or caprolactone, anionic polymerisation of ethylene oxide, as well as polymerisation of N-carboxyanhydrides of amino acids. These methods will be applied to the synthesis of polymers and block copolymers with polyester, polypeptide and/or polyether blocks. Formation and studies of self-assembled supramolecular structures based on biodegradable block copolymers and their use in the design of biomaterials with bioactive surfaces for tissue engineering and cell therapies will be also a part of the training.

In well-equipped laboratories can the students, besides chemical synthesis, obtain also experience in size exclusion chromatography (HPLC and amino acid analyser from LDC Analytical, USA, HPLC from Hitachi, Japan, or FPLC AKTA Explorer equipped with multiangle light scattering detector Wyatt), electrophoresis (Pharmacia, Sweden), ultrafiltration (Amicon), spectrophotometry and many other methods used in characterisation of polymer drugs. The students can also learn microcalorimetry, atomic force microscopy, static and dynamic light scattering and other methods convenient for the study of gene delivery systems. The supramolecular polymer structures are also studied by means of state-of-the-art time-resolved fluorescence anisotropy measurements in both the nanosecond and microsecond time regions.

Technologically important polymers

In the field of technologically important polymers we propose training oriented to these areas: Experimental study and microrheological description of the phase structure formation and evolution in immiscible polymer blends. Study of the effect of reactive and copolymer based compatibilization on supramolecular structure and properties of polymer blends. Development of rules for prediction of properties of polymer blends from the knowledge of their phase structure and properties of components. Utilization of the control of the phase structure of polymer blends by compatibilization and mixing condition at recycling of municipal plastic waste. The following methods are available for students' training: laboratory compounding and processing (Brabender Plasti-Corder, Microextruder DSM, table presses Fontijne, laboratory injection moulding machine DSM), microscopy (visible light microscopes, transmission electron microscope JEM 200CX, scanning electron microscope JSM 6400 with transmission adapter, high- and low- vacuum scanning electron microscope VEGA and low-vacuum scanning electron microscope AQUASEM), rotational and capillary rheometry (Rheometrics S IV, ARES, Rheograph 2001) and mechanical characteristics (Instron 6025, Impact tester Zwick, creep measurements).

Supramolecular order on nanoscale level is also important in conjugated polymers and in conducting polymers. Students may acquire training in synthesis and testing of conjugated polymers (p or s ) to be used as emitting or transporting layers in organic light-emitting devices, which will be fabricated and their current-voltage-electroluminescence characteristics will be measured.

Nanoscale ordering

Nanoscale ordering of block copolymers in bulk is a method of choice of generating ordered structures on the finest level of matter. Anionic polymerisation is the best means of producing polymers of convenient quality to generate such structures. Students can learn about this technique as well as be involved in the study of structural and dynamic properties of such ordered systems and their complexes and aggregates of various degrees of order. The main topics studied are supramolecular structures including micelles of amphiphilic block copolymers, bulk polymers with lamellar or cubic morphology, complexes of stereoregular polymers (conformation, polymer-solvent interactions) and nucleic acids or their models, collapse phase transitions in aqueous polymer solutions and gels, adsorption phenomena of stereoregular polymers on surfaces and microdomains and interfaces in polymer blends. As main methods used in the investigation of these topics are liquid state and solid state NMR spectroscopies, including NMR relaxation experiments, FT infrared spectroscopy, Raman spectroscopy using near-infrared and visible excitation light, quantum mechanical calculations (semiempirical and ab initio), wide-and small-angle X-ray scattering and state-of-the-art dynamic light scattering with an instrument equipped with a double goniometer for studies of oriented ordered systems.

Courses

The Training Site can offer to hosted doctoral fellows training courses "Advanced chapters in polymer science" organized on a regular basis by the institute; some of the set of 20 courses are given by members of the Training Site.

2. Specific benefits to fellows.

By undertaking part of their doctoral studies at this specific Training Site the hosted fellows will benefit from working at a large monothematically oriented institution (120 scientists) performing research in polymer science. The most important advantage of this Institute is the presence in one building of polymer chemists, physical chemists and physicists. In this way the students have the possibility of discussing easily their subject with a number of specialists in different fields and of using various experimental techniques in a short period of time. The Training Site offers to students a complex approach to supramolecular ordering, its impact on properties and functionality of the polymers and on the ways of exploiting this behaviour for specific purposes, as well as a wide range of courses. Interaction of hosted doctoral fellows with other national and international students at the Institute will also promote the concept of European science supported by the European Union.