Laboratory of fast scanning calorimetry
The laboratory was founded by grant No.14.Y26.31.0019 of the Ministry of Education and Science of the Russian Federation according to Resolution No.220 of the Government of the Russian Federation. The Laboratory of fast scanning calorimetry is based on the Department of Physical Chemistry of Kazan Federal University. Scientific director — Prof. of University of Rostock Dr. Christoph Schick, honorary doctorate of Kazan university.
Project goals and objectives:
Ultra-fast calorimetry is a novel experimental method able to obtain unique information on the processes occurring during fast heating or cooling of matter. The goal of the project is the development of the methods of ultra-fast calorimetry for investigation of thermophysical and thermochemical properties of advanced substances and materials with low thermodynamic and kinetic stability: polymers and polymer-based composites, oligo- and polypeptides, proteins, macrocyclic receptors, drug substances, ionic liquids etc. The objective of the project is acquiring new practically relevant information on the behavior of the materials during their preparation, thermal processing and application, including properties of following processes:
Another objective is the development of novel method of determination of phase transition enthalpies (condensed phase – gas and solid-liquid transitions).
Problem addressed by the scientific research project proposed herein:
Thermophysical and thermochemical properties of materials are of great importance for their application, production and processing. Materials can be exposed to rapid cooling or heating during these processes, which causes their state to depart far from equilibrium and to affect their resulting properties. Studies of basic principles of the behavior of materials in such processes not only expands our fundamental understanding of physical and chemical properties but also give basis for the directed development of novel and improvement of existing technologies of production and processing of polymers, composites and biomaterials. Ultra-fast calorimetry have shown exceptional possibilities as a key method for the researches related to the production and processing of materials (including polymers) as well as for obtaining of novel data on fundamental mechanism of phase transitions. Application of ultra-fast calorimetry allows for the investigation of processes with short characteristic times during rapid cooling or heating undetectable by conventional methods. However, application of ultra-fast calorimetry involves the problem of sample preparation and data processing therefore development of analysis methods applicable for the research on polymers, composite and biomaterials is required.
Methods of ultra-fast calorimetry will be applied for the investigation of properties of various types of materials: dispersions of polymers and drugs, oligo- and polypeptides, proteins etc. Combination of conventional methods of calorimetry and thermal analysis with ultra-fast calorimetry will enhance understanding of thermophysical and thermochemical properties of studied substances, and will allow developments of the advanced methods of obtaining of practically relevant information of properties of materials during their production, processing and application.
The choice of material classes is motivated by the significant fundamental and practical interest to the chosen substances and materials.
For example, preparation of solid dispersions of hydrophobic drugs based on biocompatible polymers – including polyvinylpyrrolidones - is important for medicine as it is related to the enhancement of solubility of active ingredients, which finally improves the bioavailability of the dispersed drug. However, one of the main problems is the relatively low kinetic stability of such solid dispersions, caused by the tendency of drugs to crystallize. Such processes can cover the timescale from seconds to years. In spite of a large number of literature devoted to investigation of the encapsulation of active ingredients with various polymers the question of optimal conditions of production of such composites is largely unsolved, as the methodology for the investigation of fast processes is not fully developed.
The main method for the investigation of the tendency of solid dispersions for crystallization is differential scanning calorimetry which allows studying relatively slow processes. Ultra-fast calorimetry is promising for the detailed research of processes in drug-polymer composites during their formation and for the determination of optimal conditions for preparation of solid dispersions. This will include a detailed study of crystal nucleation kinetics. Therefore, developing a methodology for the investigation of processes in solid dispersions of hydrophobic drugs opens the possibility of the effective development of biocompatible drug formulations with enhanced solubility and finally increased bioavailability in the human body.
At present time short chain oligopeptides are objects of intensive research because of their ability for self-organization resulting in nanostructures with unique thermal stability, rigidity (surpassing steel), stability at pH 1-14 and so on. One of the common methods for the preparation of oligopeptide-based nanostructures is heat treatment of powders or amorphous films in various conditions: vacuum, inert atmosphere, under organic or water vapours. It must be noted that the possibility of the chemical reactions between oligopeptide molecules in the solid state at elevated temperatures is often neglected. Therefore the reasons for the appearance of different nanostructures or lack of piezoelectric properties are left unexplained. To uncover this problem ultra-fast and modulated calorimetry will be used for the first time for the investigation of solid state chemical reactions in the oligopeptide-based materials which would enable (i) to determine preferable conditions for such reactions and their kinetic parameters and (ii) to obtain new types of cyclic oligopeptides and novel nanomaterials based on them.
Macrocyclic supramolecular receptors are a promising type of materials capable of “smart” behavior in the solid state, such as capability to form metastable polymorphs induced by heating and substrate (guest) interactions (binding/release). This process can have exceptional selectivity as polymorph formation may take place for a single compound in a homologous series or for similarly sized molecules with similar functional groups. The complexity of such systems actually prevents the prediction of such “smart” behavior based on the structure of the precursor molecules. Application of ultra-fast calorimetry will accelerate the search of novel receptors with smart behavior, provide new information on the kinetics of formation of metastable structures and reduce required sample size to nanograms.
Thermal properties of protein molecules are characterized by sharp changes of structure upon heating above some critical temperature – i.e. thermal denaturation. Thermal stability and denaturation of proteins in solution with organic co-solvent is much less described in the literature compared to the action of pH and ionic strength. At the same time investigations of stability and action of enzymes in water-organic media and its dependence on temperature and solvent composition is of importance for biotechnology. Besides synthetic applications, investigation of the stability of proteins in water-organic medium is important for the development of biosensors with bio-selective elements maintaining stability in the working medium as well as for the application of permeating cryoprotectants for prolonged storage of living objects and biomaterials at low temperature. Development of methods for the enhancement of protein stability in water-organic medium requires detailed investigation of the mechanisms of denaturation and renaturation as well as studying of principles determining the reversibility of denaturation. Application of ultra-fast scanning calorimetry will allow obtaining of previously unavailable information on the kinetics and mechanism of protein denaturation processes.
Many promising new materials or already used materials contain or are based on low-volatile organic components. The problem of the determination of thermochemical parameters of vaporization (sublimation) process of low-volatile materials are of great practical significance, as this process largely determines their toxicity and environmental impact. During the last two centuries a great number of experimental data on the enthalpies of the formation of vapor (via vaporization or sublimation) via direct (calorimetry) or indirect (temperature – vapor pressure dependence) methods were acquired. The majority of the methods used are applicable for thermally stable volatile compounds. For low-volatile compounds such methods as Knudsen effusion method, transpiration method, thermogravimetry and quartz microbalance are used. However, the quality of the reported data is not always sufficient.
Another equally important problem exists. The measurement of the vaporization (sublimation) enthalpies of low-volatile compounds is carried out at temperatures much higher than 298.15 K. Therefore Kirchhoff equation is used to adjust enthalpy values from the temperature of the experiment to standard temperature (298.15 K). In order to do this heat capacities of the condensed as well as the gas phase are required. While heat capacities of the condensed phase can be measured experimentally, for gas phase the possibilities are limited. Therefore heat capacities in gas phase are calculated using quantum mechanics or empirical schemes for the estimation of differences in heat capacities of the condensed and gas phase. This leads to the uncertainty in the values of vaporization and sublimation enthalpies at 298.15 K. The biggest differences arise when the experiment temperature is far from the standard temperature. Solomonov et al. proposed a method for the determination of vaporization (sublimation) enthalpies using solution enthalpy which avoids involvement of gas phase measurements. Solution enthalpy is measured at 298.15 K. This allows to overcome the problems inherent to the classical methods. Development of this novel promising method of phase transition investigation is impossible without of direct measurement of the properties of low-volatile compounds using ultra-fast calorimetry. Particularly measurements of evaporation rates at low temperatures close to the standard temperature are feasible because of the very small sample with a large surface to volume ratio.
Scientific techniques and methods that will be used to accomplish the project objectives:
The background for the desire to strive for increasing cooling and heating rates at all was, firstly, the urge that arose in the second half of the 20th century, from fundamental studies of the crystallization and melting behaviour of small systems, including the behaviour of polymer systems for which one has to cope with the presence of metastable crystallites possibly having 1, 2 or 3 nano-sized dimensions.
Secondly, the desire was to study the influence of conditions of processes in practice including processing and subsequent amorphization or partly to full crystallization of polymers, metals etc. at high cooling rates. From practice it is known that high cooling rates – in the order of typically 100 to 10 000 K/s – occur during processing by, for example, blow moulding; injection moulding etc. Obviously, many processes take place at rates ranging from slow to extremely fast, and the desire to have access to much higher rates than possible by conventional DSC, both in cooling and in heating, is a logical one. However, such high scan rates are not achievable by conventional methods.
Fulfilling of these desires only became possible during the past 20 years by the upcoming availability of Micro-Electro-Mechanical Systems (MEMS)-based sensor technology, leading to chip-based calorimeters enabling Fast Scanning Calorimetry (FSC). As a result, another jump with respect to optimal thermal characterization of properties of materials was realized by adding fast scan rates to the available range of scan rates from conventional calorimeters, both in cooling and in heating.
Scan rates of FSC typically range from approximately 1 to 1 000 K/s (in case of cooling) and 1 to 10 000 K/s (in case of heating). At the moment, at various universities, even higher, constant scan rates can be achieved, up to 1 000 000 K/s and such ultra-fast scanning calorimetry will be implemented at Kazan (Volga region) Federal University for the implementation of this project.
The recent advances of FSC thus contribute significantly to the use of calorimetry, especially in the area of understanding the relationships between kinetics of processes and prognoses based on thermodynamics of small, nano- to micrometer-sized systems as occurring in polymer materials and biomolecules.
As an example, by matching the heating rate in such a way that it can compete with the specific rates of reorganization; of melting; of chemical reactions; of evaporation; of denaturation; of decomposition etc., influence of these processes can be suppressed or studied in detail.
As another example, the capability of fast cooling is a major advantage of FSC with respect to crystallization and vitrification phenomena. By applying appropriate cooling rates for many substances, the critical cooling rate for crystallization can be surpassed, resulting in an amorphous sample. This is an extremely useful capability because it enables in general the study of all kinds of subsequent phenomena like (de)vitrification, crystallization, and melting. Especially, subsequent measurement of overall crystallization and nucleation rates as function of temperature has become a major topic.
In addition, the shortest times, reachable by FSC, turn out to be similar to the longest times accessible by high-efficient dynamic Monte Carlo simulations of polymer crystallization leading to a powerful tool for interpretation and prediction of calorimetric experiment results regarding kinetics, and more successful than analytical approaches applied hitherto.
In addition to the aforementioned capabilities, FSC is also paramount in case maximal sensitivity is needed, in order to enable study of very small-mass samples, like thin films; fractions obtained by separation techniques; remnants for forensic investigations etc.
In the near future, the impact of FSC will increase along various routes. Other systems like pharmaceuticals, food, are expected to be studied as well. Thus, a thorough evaluation of both thermal behaviour and (non-) structural morphology of systems at high scan rates will become one of the topics in the next decade.
Ultra-fast calorimetry will be used in combination with conventional methods of calorimetry and thermal analysis as well as spectral and structural methods for as complete as possible description of processes and changes in properties of substances during thermal transitions.
Experimental methods will be combined with contemporary approaches for simulation and data processing and visualization.
