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Natural raw materials as plants contain a wide range and type of valuable and biologically active compounds and also various extraction methods are applied in industry and are studied at research and development ranging from steam distillation through solvent extractions to pressurized liquid extraction and supercritical fluid extraction. Selection between the methods is in principle based on the technological feasibility, among the suitable methods selection is made upon economics and availability. While simulation based economical calculations are well established is certain cases like distillation or heat exchanger networks, similar simulation methodology is not readily available for plant extractions. There is a significant lack on phase equilibrium data and/or assumption methodology of a complex and very heterogeneous mixture like soluble plant constituent, and furthermore, the mass transfer limitations must be also taken into account. The PhD fellow will develop a suitable method to simulate the various plant extraction methods in ASPEN Hysis, and will perform necessary measurements (e.g. phase equilibrium measurements, characterisation of the solid plant material) and he/she will compare the simulation results with experimental extraction data.

Preparation of enantiopure chemicals is still a hot topic in research although there is already a large chiral market. In principle two routes are possible: the synthetic route and isolation from natural sources, typically from plant biomass. Isolation from natural sources is an interesting route not only to obtain single chiral components, but also to prepare mixtures having certain bioactivities. Enantiomer separation by the synthetic route is performed typically either by chiral catalysis of a reaction with a prochiral substrate or by optical resolution of a racemate. Regardless which method is applied, in most of the cases only enantiomeric mixtures are produced in the first step. This is followed by a further purification process, most typically by several recrystallizations. These are time and solvent intensive steps, resulting in significant amounts of the expensive enantiomers or diastereomers dissolved in the solvent phase, while solvent residues are present in significant amounts in the solid phase. After achieving the enantiopure final product size reduction is also typically required before formulation, in the pharma industry at least. Antisolvent fractionation with supercritical carbon dioxide recently gained attention in the scientific literature. The possibility of further purifying either a mixture of the diastereomeric salts of a compound or an enantiomeric mixture can be investigated by recording the ee1 –ee0 or de1 – de0 diagrams of the compounds, where ee and de are enantiomeric and diastereomeric excess, respectively. Such diagrams are also useful in determining the limits of further purification, similarly to those observed in atmospheric resolutions. It must be noted, that antisolvent fractionation is based on fast oversaturation and immediate precipitation followed by an extraction step. It is worthwhile to systematically study when the kinetic effects, and when the thermodynamics of the system (represented by the melting point phase diagrams) are dominant. The process can be influenced strongly by the solubility of the components (the pure enantiomers and the racemic forms or the diastereomeric salts) in supercritical carbon dioxide.

The research is assumed to lead to a better understanding how the chemical equilibrium, the solubility of the compounds present and the kinetics of the process influence the efficiency of the enantiomeric/diastereomeric enhancement.

Most relevant publications: 

Márton Kőrösi, János Madarász, Tamás Sohajda, Edit Székely, Fast further purification of diastereomeric salts of a nonracemic acid by gas antisolvent fractionation, CHIRALITY: THE PHARMACOLOGICAL BIOLOGICAL AND CHEMICAL CONSEQUENCES OF MOLECULAR ASYMMETRY 29:(10) pp. 610-615. (2017)

Márton Kőrösi, János Madarász, Tamás Sohajda, Edit Székely, A fast, new method to enhance the enantiomeric purity of non-racemic mixtures: self-disproportionation of enantiomers in the gas antisolvent fractionation of chlorine-substituted mandelic acid derivatives, TETRAHEDRON-ASYMMETRY Paper TETASY 59695. (2017)

 

Objectives: development of supercritical diastereomer crystallization methods competitive in efficiency to the traditional solvent based crystallizations and having lower environmental effects.

Tasks and methodology:

  • Literature survey
  • Screening of promising resolving agents for all racemates (4 to 6). Selection of the two best pairs.
  • Measurement of solubility of the selected racemate(s) in CO2 and in CO2-solvent mixtures.
  • Development of the high pressure diastereomeric salt precipitation processes. (separately for the two pairs)
  • Critical evaluation and simple mathematical modelling of results. 

Results:

  • racemate – resolving agent pairs grouped to no salt / no enantioselectivity / poor enantioselectivity / good enantioselectivity groups
  • timeframe of salt formation mapped and analytical methodology developed
  • high pressure diastereomeric salt formation process developed and optimised

Selected publications: 

Amit D Zodge, Petra Bombicz, Edit Székely, György Pokol, János Madarász, Structural, analytical and DSC references to resolution of 2-methoxy-2-phenylacetic acid with chiral 1-cyclohexylethylamines through gas-antisolvent precipitation THERMOCHIMICA ACTA 648: pp. 23-31. (2017)

A Zodge, M Kőrösi, M Tárkányi, J Madarász, I M Szilágyi, T Sohajda, E Székely, Gas Antisolvent Approach for the Precipitation of -Methoxyphenylacetic Acid – (R)-1-Cyclohexylethylamine Diateromeric Salt CHEMICAL AND BIOCHEMICAL ENGINEERING QUARTERLY 31:(3) (2017)

László Lőrincz, György Bánsághi, Máté Zsemberi, Sandra de Simon Brezmes, Imre Miklós Szilágyi, János Madarász, Tamás Sohajda, Edit Székely, Diastereomeric salt precipitation based resolution of ibuprofen by gas antisolvent method, JOURNAL OF SUPERCRITICAL FLUIDS 118: pp. 48-53. (2016)

Az enzimek és egyéb fehérjék előállítása, alkalmazása a modern iparban mind a vegyipari, mind az orvosi területen nagyon jelentős és innovatív terület. Ezek a fehérjék azonban érzékenyek az extrém hatásokra, mint a magas hőmérséklet, szerves oldószerek, stb. Ennek a limitációnak a feloldására nyújthat a szuperkritikus szén-dioxid megfelelő, környezeti szempontból is előnyös megoldási lehetőséget.

Néhány publikáció a témakörben: 

Varga Zsófia, Kmecz Ildikó, Szécsényi Ágnes, Székely Edit, Neat lipase-catalysed kinetic resolution of racemic 1-phenylethanol and a straightforward modelling of the reaction, BIOCATALYSIS AND BIOTRANSFORMATION 56: pp. 1-7. (2017)

Székely E, Utczás M, Simándi B Kinetic enzymatic resolution in scCO2 – Design of continuous reactor based on batch experiments JOURNAL OF SUPERCRITICAL FLUIDS 79: pp. 127-132. (2012)

A szuperkritikus szén-dioxidos extrakció egy modern, környezetkímélő elválasztási módszer. Napjainkban már elterjedten alkalmazzák ipari méretben is, elsősorban élelmiszeripari vagy kozmetikai felhasználású termékek előállítására. Előnye, hogy így tiszta, szerves oldószernyomoktól mentes termék állítható elő, aminek értéke sokkal nagyobb, mint a hagyományos oldószerekkel előállított kivonatoké.

A kutatómunka célja értékes növényi anyagok (pl. antioxidánsok, színezékek) szuperkritikus extrakciójának vizsgálata gyógyászati, kozmetikai és élelmiszeripari célra alkalmas adalékok előállítása céljából. A doktoráns feladata a szuperkritikus extrakció optimális műveleti paramétereinek meghatározása, a termékek (extrakt és maradék) minőségi összehasonlítása a hagyományos módon (vízgőz-desztillációval és oldószeres extrakcióval) nyerhető termékekkel.

 

   
© BME, Research Group on Supercritical Fluids, 2015