Model validation for the biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor

Enzimi su biološki katalizatori koji su prisutni u živim stanicama i neophodni su za život kakav poznajemo. Reakcije u kojima su prisutni enzimi potrebno je dobro istražiti i okarakterizirati kako bi se mogle provoditi u industrijskim mjerilima. Prednost uporabe enzima u biokatalitičkim reakcijima leži u činjenici da su djelotvnorni i pri vrlo blagim uvjetima, puno blažim od kemijskih katalizatora. Potrebno je obratiti pažnju i na aktivnost enzima u različitim reakcijskim uvjetima (temperatura, koncentracija supstrata, pH, zasićenost kisikom) jer optimizacijom reakcijskih uvjeta omogućujemo maksimalan prinos željenog produkta i smanjenje nastanka neželjenog ili štetnog nusprodukta. Fluorirani aromatski spojevi su iznimno važni u farmaceutskoj industriji kao prekursori i kao građevni blokovi. Bitno je da takvi spojevi budu optički čisti jer je poznato da dva enantiomera mogu imati znatno različita svojstva i biološko djelovanje, često štetno i toksično. Jedna od metoda sinteze takvih spojeva uključuje korištenje enzima halogenhidrin-dehalogenaze (HHDH). U ovom radu proučavana je reakcija otvaranja epoksidnog prstena, fluoriranog derivata stiren oksida uz azid kao nukleofil prilikom čega nastaje fluorirani azidoalkohol. Reakcija je katalizirana enzimom HHDH (C-tip) koji je poznat i pod nazivom HheC-W249P. Cilj ovog rada bio je validirati matematički model biokatalitičke sinteze (R)-2-azido-1-(4-trifluorometil-fenil)-etanola u šaržnom reaktoru. Model je uspješno validiran provedbom reakcije u pet različitih kotlastih reaktora s različitim početnim uvjetima u reaktoru. Uzorci reakcijske smjese su analizirani na tekućinskom kromatografu visoke djelotvornosti. Praćena je i stabilnost enzima pri različitim uvjetima prilikom čega je pokazano da početni uvjeti u reaktoru ne utječu značajno na stabilnost enzima. Stabilnost enzima se pratila spektrofotometrijskom metodom.Enzymes are biological catalysts that are present in living cells and are necessary for life as we know it. Reactions in which enzymes are present need to be well investigated and characterized in order to be carried out on an industrial scale. The advantage of using enzymes in biocatalytic reactions lies in the fact that they are effective even under very mild conditions, much milder than catalysts of chemical reactions. It is necessary to pay attention to the activity of enzymes in different reaction conditions (temperature, substrate concentration, pH, oxygen saturation) because by optimizing the reaction conditions we enable maximum yield of the desired product and reduction of unwanted or harmful by-products. Fluorinated aromatic compounds are extremely important in the pharmaceutical industry as precursors and as building blocks. It is important that such compounds be optically pure because it is known that the two enantiomers can have significantly different properties and biological effect, often harmful and toxic. One of the methods of synthesis of such compounds is the use of the enzyme halohydrin-dehalogenase (HHDH). In this paper, the reaction of opening an epoxy ring, a fluorinated derivative of styrene oxide with an azide as a nucleophile, during which a fluorinated azidoalcohol is formed, was studied. The reaction is catalyzed by the HHDH (C-type) enzyme also known as HheC-W249P. The aim of this work was to validate a mathematical model of biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor. The model was successfully validated by carrying out the reaction in five different batch reactors with different initial conditions in the reactor. Samples of the reaction mixture were analyzed on a high performance liquid chromatograph. The stability of the enzyme under different conditions was also monitored, and it was shown that the initial conditions in the reactor did not significantly affect the stability of the enzyme. Enzyme stability was monitored by spectrophotometric method

Solid-liquid equilibria in mixtures of long-chain alkanes and long-chain alcohols

U ovom radu su na nekoliko primjera opisani načini modeliranja fazne ravnoteže kapljevina‐krutina u sustavima s dugolančanim organskim molekulama. Podatci za temperaturu taljenja kao funkciju sastava preuzeti su iz literature i na temelju tih podataka modelirani su fazni dijagrami u sustavima koji uz n‐oktanol kao prvu komponentu sadrže još i ravnolančani alkan: n‐oktan (2), n‐dekan, n‐undekan, n‐dodekan, n‐tetradekan odnosno n‐heksadekan. Za opis neidalnosti kapljevite faze testirani su sljedeći modeli koeficijenta aktivnosti: troparametarski i četveroparametarski Redlich‐Kisterov model, Wilsonov model, model NRTL, model NRTL‐MK, model UNIQUAC i model UNIFAC. Kao rezultat modeliranja dobivene su ravnotežne krivulje taljenja koji nastoje što bolje opisati eksperimentalne podatke o ovisnosti tališta o sastavu otopine. Iz rezultata je vidljivo da Redlich‐Kisterov model (troparametarski i četveroparametarski) te model NRTL‐MK bolje opisuju sve sustave, a Wilsonov model, model NRTL, model UNIQUAC i model UNIFAC nešto lošije zadovoljavaju podudarnost krivulja modela i eksperimentalnih točaka.This paper describes, in several examples, procedures for modeling liquid‐solid phase equilibria in systems with long‐chain organic molecules. Experimental data for melting point as a function of system composition were taken from literature and on the basis of that data phase diagrams were modeled for systems containing n‐octanol as the first component and long‐chain n‐alkanes: n‐octane, n‐decane, n‐undecane, n‐dodecane, n‐tetradecane or n‐hexadecane as the second component. In order to describe unideal behavior of liquid phase the following activity coefficient models were tested: three‐parameter and four‐parameter Redlich‐Kister model, Wilson model, NRTL model, NRTL‐MK model, UNIQUAC model and UNIFAC model. As a result of modeling, equilibrium liquidus curves were obtained which tend to describe the experimental data in the best possible way. The results show that the Redlich‐Kister model (three‐parameter and four‐parameter) and the NRTL‐MK model can describe fairly all investigated systems; Wilson, NRTL, UNIQUAC and UNIFAC models describe the experimental data slightly worse

Solid-liquid equilibria in mixtures of long-chain alkanes and long-chain alcohols

U ovom radu su na nekoliko primjera opisani načini modeliranja fazne ravnoteže kapljevina‐krutina u sustavima s dugolančanim organskim molekulama. Podatci za temperaturu taljenja kao funkciju sastava preuzeti su iz literature i na temelju tih podataka modelirani su fazni dijagrami u sustavima koji uz n‐oktanol kao prvu komponentu sadrže još i ravnolančani alkan: n‐oktan (2), n‐dekan, n‐undekan, n‐dodekan, n‐tetradekan odnosno n‐heksadekan. Za opis neidalnosti kapljevite faze testirani su sljedeći modeli koeficijenta aktivnosti: troparametarski i četveroparametarski Redlich‐Kisterov model, Wilsonov model, model NRTL, model NRTL‐MK, model UNIQUAC i model UNIFAC. Kao rezultat modeliranja dobivene su ravnotežne krivulje taljenja koji nastoje što bolje opisati eksperimentalne podatke o ovisnosti tališta o sastavu otopine. Iz rezultata je vidljivo da Redlich‐Kisterov model (troparametarski i četveroparametarski) te model NRTL‐MK bolje opisuju sve sustave, a Wilsonov model, model NRTL, model UNIQUAC i model UNIFAC nešto lošije zadovoljavaju podudarnost krivulja modela i eksperimentalnih točaka.This paper describes, in several examples, procedures for modeling liquid‐solid phase equilibria in systems with long‐chain organic molecules. Experimental data for melting point as a function of system composition were taken from literature and on the basis of that data phase diagrams were modeled for systems containing n‐octanol as the first component and long‐chain n‐alkanes: n‐octane, n‐decane, n‐undecane, n‐dodecane, n‐tetradecane or n‐hexadecane as the second component. In order to describe unideal behavior of liquid phase the following activity coefficient models were tested: three‐parameter and four‐parameter Redlich‐Kister model, Wilson model, NRTL model, NRTL‐MK model, UNIQUAC model and UNIFAC model. As a result of modeling, equilibrium liquidus curves were obtained which tend to describe the experimental data in the best possible way. The results show that the Redlich‐Kister model (three‐parameter and four‐parameter) and the NRTL‐MK model can describe fairly all investigated systems; Wilson, NRTL, UNIQUAC and UNIFAC models describe the experimental data slightly worse

Model validation for the biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor

Enzimi su biološki katalizatori koji su prisutni u živim stanicama i neophodni su za život kakav poznajemo. Reakcije u kojima su prisutni enzimi potrebno je dobro istražiti i okarakterizirati kako bi se mogle provoditi u industrijskim mjerilima. Prednost uporabe enzima u biokatalitičkim reakcijima leži u činjenici da su djelotvnorni i pri vrlo blagim uvjetima, puno blažim od kemijskih katalizatora. Potrebno je obratiti pažnju i na aktivnost enzima u različitim reakcijskim uvjetima (temperatura, koncentracija supstrata, pH, zasićenost kisikom) jer optimizacijom reakcijskih uvjeta omogućujemo maksimalan prinos željenog produkta i smanjenje nastanka neželjenog ili štetnog nusprodukta. Fluorirani aromatski spojevi su iznimno važni u farmaceutskoj industriji kao prekursori i kao građevni blokovi. Bitno je da takvi spojevi budu optički čisti jer je poznato da dva enantiomera mogu imati znatno različita svojstva i biološko djelovanje, često štetno i toksično. Jedna od metoda sinteze takvih spojeva uključuje korištenje enzima halogenhidrin-dehalogenaze (HHDH). U ovom radu proučavana je reakcija otvaranja epoksidnog prstena, fluoriranog derivata stiren oksida uz azid kao nukleofil prilikom čega nastaje fluorirani azidoalkohol. Reakcija je katalizirana enzimom HHDH (C-tip) koji je poznat i pod nazivom HheC-W249P. Cilj ovog rada bio je validirati matematički model biokatalitičke sinteze (R)-2-azido-1-(4-trifluorometil-fenil)-etanola u šaržnom reaktoru. Model je uspješno validiran provedbom reakcije u pet različitih kotlastih reaktora s različitim početnim uvjetima u reaktoru. Uzorci reakcijske smjese su analizirani na tekućinskom kromatografu visoke djelotvornosti. Praćena je i stabilnost enzima pri različitim uvjetima prilikom čega je pokazano da početni uvjeti u reaktoru ne utječu značajno na stabilnost enzima. Stabilnost enzima se pratila spektrofotometrijskom metodom.Enzymes are biological catalysts that are present in living cells and are necessary for life as we know it. Reactions in which enzymes are present need to be well investigated and characterized in order to be carried out on an industrial scale. The advantage of using enzymes in biocatalytic reactions lies in the fact that they are effective even under very mild conditions, much milder than catalysts of chemical reactions. It is necessary to pay attention to the activity of enzymes in different reaction conditions (temperature, substrate concentration, pH, oxygen saturation) because by optimizing the reaction conditions we enable maximum yield of the desired product and reduction of unwanted or harmful by-products. Fluorinated aromatic compounds are extremely important in the pharmaceutical industry as precursors and as building blocks. It is important that such compounds be optically pure because it is known that the two enantiomers can have significantly different properties and biological effect, often harmful and toxic. One of the methods of synthesis of such compounds is the use of the enzyme halohydrin-dehalogenase (HHDH). In this paper, the reaction of opening an epoxy ring, a fluorinated derivative of styrene oxide with an azide as a nucleophile, during which a fluorinated azidoalcohol is formed, was studied. The reaction is catalyzed by the HHDH (C-type) enzyme also known as HheC-W249P. The aim of this work was to validate a mathematical model of biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor. The model was successfully validated by carrying out the reaction in five different batch reactors with different initial conditions in the reactor. Samples of the reaction mixture were analyzed on a high performance liquid chromatograph. The stability of the enzyme under different conditions was also monitored, and it was shown that the initial conditions in the reactor did not significantly affect the stability of the enzyme. Enzyme stability was monitored by spectrophotometric method

Solid-liquid equilibria in mixtures of long-chain alkanes and long-chain alcohols

U ovom radu su na nekoliko primjera opisani načini modeliranja fazne ravnoteže kapljevina‐krutina u sustavima s dugolančanim organskim molekulama. Podatci za temperaturu taljenja kao funkciju sastava preuzeti su iz literature i na temelju tih podataka modelirani su fazni dijagrami u sustavima koji uz n‐oktanol kao prvu komponentu sadrže još i ravnolančani alkan: n‐oktan (2), n‐dekan, n‐undekan, n‐dodekan, n‐tetradekan odnosno n‐heksadekan. Za opis neidalnosti kapljevite faze testirani su sljedeći modeli koeficijenta aktivnosti: troparametarski i četveroparametarski Redlich‐Kisterov model, Wilsonov model, model NRTL, model NRTL‐MK, model UNIQUAC i model UNIFAC. Kao rezultat modeliranja dobivene su ravnotežne krivulje taljenja koji nastoje što bolje opisati eksperimentalne podatke o ovisnosti tališta o sastavu otopine. Iz rezultata je vidljivo da Redlich‐Kisterov model (troparametarski i četveroparametarski) te model NRTL‐MK bolje opisuju sve sustave, a Wilsonov model, model NRTL, model UNIQUAC i model UNIFAC nešto lošije zadovoljavaju podudarnost krivulja modela i eksperimentalnih točaka.This paper describes, in several examples, procedures for modeling liquid‐solid phase equilibria in systems with long‐chain organic molecules. Experimental data for melting point as a function of system composition were taken from literature and on the basis of that data phase diagrams were modeled for systems containing n‐octanol as the first component and long‐chain n‐alkanes: n‐octane, n‐decane, n‐undecane, n‐dodecane, n‐tetradecane or n‐hexadecane as the second component. In order to describe unideal behavior of liquid phase the following activity coefficient models were tested: three‐parameter and four‐parameter Redlich‐Kister model, Wilson model, NRTL model, NRTL‐MK model, UNIQUAC model and UNIFAC model. As a result of modeling, equilibrium liquidus curves were obtained which tend to describe the experimental data in the best possible way. The results show that the Redlich‐Kister model (three‐parameter and four‐parameter) and the NRTL‐MK model can describe fairly all investigated systems; Wilson, NRTL, UNIQUAC and UNIFAC models describe the experimental data slightly worse

Model validation for the biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor

Enzimi su biološki katalizatori koji su prisutni u živim stanicama i neophodni su za život kakav poznajemo. Reakcije u kojima su prisutni enzimi potrebno je dobro istražiti i okarakterizirati kako bi se mogle provoditi u industrijskim mjerilima. Prednost uporabe enzima u biokatalitičkim reakcijima leži u činjenici da su djelotvnorni i pri vrlo blagim uvjetima, puno blažim od kemijskih katalizatora. Potrebno je obratiti pažnju i na aktivnost enzima u različitim reakcijskim uvjetima (temperatura, koncentracija supstrata, pH, zasićenost kisikom) jer optimizacijom reakcijskih uvjeta omogućujemo maksimalan prinos željenog produkta i smanjenje nastanka neželjenog ili štetnog nusprodukta. Fluorirani aromatski spojevi su iznimno važni u farmaceutskoj industriji kao prekursori i kao građevni blokovi. Bitno je da takvi spojevi budu optički čisti jer je poznato da dva enantiomera mogu imati znatno različita svojstva i biološko djelovanje, često štetno i toksično. Jedna od metoda sinteze takvih spojeva uključuje korištenje enzima halogenhidrin-dehalogenaze (HHDH). U ovom radu proučavana je reakcija otvaranja epoksidnog prstena, fluoriranog derivata stiren oksida uz azid kao nukleofil prilikom čega nastaje fluorirani azidoalkohol. Reakcija je katalizirana enzimom HHDH (C-tip) koji je poznat i pod nazivom HheC-W249P. Cilj ovog rada bio je validirati matematički model biokatalitičke sinteze (R)-2-azido-1-(4-trifluorometil-fenil)-etanola u šaržnom reaktoru. Model je uspješno validiran provedbom reakcije u pet različitih kotlastih reaktora s različitim početnim uvjetima u reaktoru. Uzorci reakcijske smjese su analizirani na tekućinskom kromatografu visoke djelotvornosti. Praćena je i stabilnost enzima pri različitim uvjetima prilikom čega je pokazano da početni uvjeti u reaktoru ne utječu značajno na stabilnost enzima. Stabilnost enzima se pratila spektrofotometrijskom metodom.Enzymes are biological catalysts that are present in living cells and are necessary for life as we know it. Reactions in which enzymes are present need to be well investigated and characterized in order to be carried out on an industrial scale. The advantage of using enzymes in biocatalytic reactions lies in the fact that they are effective even under very mild conditions, much milder than catalysts of chemical reactions. It is necessary to pay attention to the activity of enzymes in different reaction conditions (temperature, substrate concentration, pH, oxygen saturation) because by optimizing the reaction conditions we enable maximum yield of the desired product and reduction of unwanted or harmful by-products. Fluorinated aromatic compounds are extremely important in the pharmaceutical industry as precursors and as building blocks. It is important that such compounds be optically pure because it is known that the two enantiomers can have significantly different properties and biological effect, often harmful and toxic. One of the methods of synthesis of such compounds is the use of the enzyme halohydrin-dehalogenase (HHDH). In this paper, the reaction of opening an epoxy ring, a fluorinated derivative of styrene oxide with an azide as a nucleophile, during which a fluorinated azidoalcohol is formed, was studied. The reaction is catalyzed by the HHDH (C-type) enzyme also known as HheC-W249P. The aim of this work was to validate a mathematical model of biocatalytic synthesis of (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in a batch reactor. The model was successfully validated by carrying out the reaction in five different batch reactors with different initial conditions in the reactor. Samples of the reaction mixture were analyzed on a high performance liquid chromatograph. The stability of the enzyme under different conditions was also monitored, and it was shown that the initial conditions in the reactor did not significantly affect the stability of the enzyme. Enzyme stability was monitored by spectrophotometric method

Tea Zec, sopran : diplomski ispit

Diplomski ispit Tee Zec (sopran), studentice MA. Ispit je održan u Kazalištu Mala scena u Zagrebu 17.6.2021. Klavirska pratnja: Simon Peter Dešpalj; gosti izvođači: Siniša Galović (tenor), Ivana Miletić (mezzosopran), Veronika Hardy (sopran), Emanuel Tomljenović (tenor), Boris Beus (bas bariton), Martina Barišić (sopran), Lucija Klarić (mezzosopran); mentor: Renata Pokupić. Program: Wolfgang Amadeus Mozart: Idomeneo, re di Creta (uloga Elettre)

Koncert na dar : studenti Muzičke akademije uz Zagrebačke soliste (Zagrebački solisti i studenti Muzičke akademije Sveučilišta u Zagrebu, 12. 1. 2022.)

Koncert je održan na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 12. 1. 2022. Izvođači: Zagrebački solisti, studenti Muzičke akademije Sveučilišta u Zagrebu, solisti Luka Halužan (truba), Emanuel Tomljenović (tenor), Lucija Kašnar (klavir) i Marko Glogović (violina). Program: 1. Giuseppe Tartini (transkripcija: J. Golob): Koncert za trubu i gudače u D-duru (Allegro – Andante – Allegro grazioso) (solist: Luka Halužan); 2. Johann Sebastian Bach: Ich will nur dir zu ehren leben, arija iz Božićnog oratorija (solist: Emanuel Tomljenović); 3. Wolfgang Amadeus Mozart (obr. Vinzenz Lahner): Koncert za glasovir i orkestar u Es-duru, KV 271, obrada za glasovir i gudače (Rondo. Presto) (solist: Lucija Kašnar); 4. Tomislav Uhlik: Gospon Fašnik, kolaž za violinu i gudače (solist: Marko Glogović); 5. David Batinić: Passacaglia za gudače (praizvedba); 6. Luigi Boccherini: Simfonija u d-molu, op. 12 br. 4, "La casa del Diavolo", obrada za gudače (Andante sostenuto-Allegro Assai – Andantino con moto – Andante sostenuto-Allegro con molto)

Koncert na dar : studenti Muzičke akademije uz Zagrebačke soliste (Zagrebački solisti i studenti Muzičke akademije Sveučilišta u Zagrebu, 12. 1. 2022.)

Koncert je održan na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 12. 1. 2022. Izvođači: Zagrebački solisti, studenti Muzičke akademije Sveučilišta u Zagrebu, solisti Luka Halužan (truba), Emanuel Tomljenović (tenor), Lucija Kašnar (klavir) i Marko Glogović (violina). Program: 1. Giuseppe Tartini (transkripcija: J. Golob): Koncert za trubu i gudače u D-duru (Allegro – Andante – Allegro grazioso) (solist: Luka Halužan); 2. Johann Sebastian Bach: Ich will nur dir zu ehren leben, arija iz Božićnog oratorija (solist: Emanuel Tomljenović); 3. Wolfgang Amadeus Mozart (obr. Vinzenz Lahner): Koncert za glasovir i orkestar u Es-duru, KV 271, obrada za glasovir i gudače (Rondo. Presto) (solist: Lucija Kašnar); 4. Tomislav Uhlik: Gospon Fašnik, kolaž za violinu i gudače (solist: Marko Glogović); 5. David Batinić: Passacaglia za gudače (praizvedba); 6. Luigi Boccherini: Simfonija u d-molu, op. 12 br. 4, "La casa del Diavolo", obrada za gudače (Andante sostenuto-Allegro Assai – Andantino con moto – Andante sostenuto-Allegro con molto)

Tea Zec, sopran : diplomski ispit

Diplomski ispit Tee Zec (sopran), studentice MA. Ispit je održan u Kazalištu Mala scena u Zagrebu 17.6.2021. Klavirska pratnja: Simon Peter Dešpalj; gosti izvođači: Siniša Galović (tenor), Ivana Miletić (mezzosopran), Veronika Hardy (sopran), Emanuel Tomljenović (tenor), Boris Beus (bas bariton), Martina Barišić (sopran), Lucija Klarić (mezzosopran); mentor: Renata Pokupić. Program: Wolfgang Amadeus Mozart: Idomeneo, re di Creta (uloga Elettre)