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Mojtaba Shamsipur - One of the best experts on this subject based on the ideXlab platform.
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separation and preconcentration of trace gallium and indium by amberlite xad 7 resin impregnated with a new hexadentates Naphthol Derivative schiff base
Separation Science and Technology, 2009Co-Authors: Kamal Saberyan, Mojtaba Shamsipur, Ehsan Zolfonoun, Masoud SalavatiniasariAbstract:Abstract A new chelating polymeric sorbent has been developed using impregnation of Amberlite XAD-7 resin with a newly-synthesized hexadentates Naphthol-Derivative Schiff base 1-[(1E,9E)-10-(2-hydroxy-1-naphthyl)-4,7-dioxa-2,9-diaza-1,9-decadienyl]-2-naphth (EHND). The impregnated resin showed high binding affinity for Ga(III) and In(III) ions and was used for their preconcentration prior to determination by flame AAS. The optimum pH values for the quantitative sorption of Ga(III) and In(III) are 4.0–6.0 and 4.5–8.0, respectively, and their desorptions can be achieved by using 5 mL of 1 M HNO3. The sorption capacities of the resin for gallium and indium were 1.1 and 1.3 mg g−1, respectively. The enrichment factor for preconcentration of gallium and indium was found to be 200. The precision of the method, evaluated as the relative standard deviation obtained by analyzing a series of ten replicates, was below 2.5% for both elements. The practical applicability of the polymer was tested with synthetic seawat...
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liquid liquid distribution of the tetravalent zirconium hafnium and thorium with a new tetradentate Naphthol Derivative schiff base
Bulletin of The Korean Chemical Society, 2008Co-Authors: Kamal Saberyan, Mojtaba Shamsipur, Ehsan Zolfonoun, Masoud SalavatiniasariAbstract:A fundamental study was developed concerning the novel solvent extraction of the tetravalent metal ions;zirconium(IV), hafnium(IV) and thorium(IV). Their extraction behavior in toluene was investigated with arecently synthesized Naphthol-Derivative Schiff base, 1-({[4-(4-{[(E)-1-(2-hydroxy-1-naphthyl)methyliden]-amino}phenoxy) phenyl]imino}methyl)-2-Naphthol (HAPMN). The spectrophotometrical examination of thecomplex formation between HAPMN and the Zr(IV), Hf(IV) and Th(IV) ions in acetonitrile revealed theformation of stable 1:1 complexes in the solution. After the thorium extraction in toluene, it was found that[Th(OH)
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Liquid-liquid Distribution of the Tetravalent Zirconium, Hafnium and Thorium with a New Tetradentate Naphthol-Derivative Schiff Base
2007Co-Authors: Kamal Saberyan, Mojtaba Shamsipur, Ehsan Zolfonoun, Masoud Salavati-niasariAbstract:A fundamental study was developed concerning the novel solvent extraction of the tetravalent metal ions; zirconium(IV), hafnium(IV) and thorium(IV). Their extraction behavior in toluene was investigated with a recently synthesized Naphthol-Derivative Schiff base, 1-({[4-(4-{[(E)-1-(2-hydroxy-1-naphthyl)methyliden]-amino}phenoxy) phenyl]imino}methyl)-2-Naphthol (HAPMN). The spectrophotometrical examination of th
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uo 2 2 ion selective membrane electrode based on a Naphthol Derivative schiff s base 2 2 1 2 ethandiyl bis nitriloethylidene bis 1 naphthalene
Bulletin of The Korean Chemical Society, 2004Co-Authors: Mojtaba Shamsipur, Hossein Naeimi, Mahboubeh Saeidi, Abdullah Yari, Ali Yaganehfaal, Mohammad Hossein Mashhadizadeh, Gholamhasan Azimi, Hashem SharghiAbstract:A new PVC membrane electrode for UO 2 2+ ion based on 2,2'-[1,2-ethanediyl bis (nitriloethylidene)]bis(1-naphthalene) as a suitable ionophore was prepared. The electrode exhibites a Nernstian response for UO 2 2+ ion over awide concentration range (1.0 x 10 - 1 -1.0 x 10 - 7 M) with a slope of 28.5 ′ 0.8 mV/decade. The limit of detection is 7.0 x 10 - 8 M. The electrode has a response time of < 20 s and a useful working pH range of 3-4. The proposed membrane sensor shows good discriminating abilities towards UO 2 2+ ion with regard to several alkali, alkaline earth transition and heavy metal ions. It was successfully used to the recovery of uranyl ion from, tap water and, as an indicator electrode, in potentiometric titration of UO 2 2+ ion with Piroxycam.
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selective determination of trace copper ii by cathodic adsorptive stripping voltammetry with a Naphthol Derivative schiff s base
Annali Di Chimica, 2003Co-Authors: Mojtaba Shamsipur, Hashem Sharghi, Mahboubeh Saeidi, Hossein NaeimiAbstract:A selective and sensitive stripping voltammetric method for the determination of trace amounts of copper(II) with a recently synthesized Naphthol-Derivative Schiff's base (2,2'-[1,2-ethanediylbis(nitriloethylidyne)]bis(1-naphthalene)) is presented. The method is based on adsorptive accumulation of the resulting copper-Schiff's base complex on a hanging mercury drop electrode, followed by the stripping voltammetric measurement at the reduction current of adsorbed complex at -0.15 V (vs. Ag/AgCl). The optimal conditions for the stripping analysis of copper include pH 5.5 to 6.5, 8 microM Schiff's base and an accumulation potential of -0.05 V (vs. Ag/AgCI). The peak current is linearly proportional to the copper concentration over a range 2.3-50.8 ng ml(-1) with a limit of detection of 1.9 ng ml(-1). The accumulation time and RSD are 90 s and (3.2-3.5)%, respectively. The method was applied to the determination of copper in some analytical grade salts, tap water, human serum and sheep's liver.
Hossein Naeimi - One of the best experts on this subject based on the ideXlab platform.
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uo 2 2 ion selective membrane electrode based on a Naphthol Derivative schiff s base 2 2 1 2 ethandiyl bis nitriloethylidene bis 1 naphthalene
Bulletin of The Korean Chemical Society, 2004Co-Authors: Mojtaba Shamsipur, Hossein Naeimi, Mahboubeh Saeidi, Abdullah Yari, Ali Yaganehfaal, Mohammad Hossein Mashhadizadeh, Gholamhasan Azimi, Hashem SharghiAbstract:A new PVC membrane electrode for UO 2 2+ ion based on 2,2'-[1,2-ethanediyl bis (nitriloethylidene)]bis(1-naphthalene) as a suitable ionophore was prepared. The electrode exhibites a Nernstian response for UO 2 2+ ion over awide concentration range (1.0 x 10 - 1 -1.0 x 10 - 7 M) with a slope of 28.5 ′ 0.8 mV/decade. The limit of detection is 7.0 x 10 - 8 M. The electrode has a response time of < 20 s and a useful working pH range of 3-4. The proposed membrane sensor shows good discriminating abilities towards UO 2 2+ ion with regard to several alkali, alkaline earth transition and heavy metal ions. It was successfully used to the recovery of uranyl ion from, tap water and, as an indicator electrode, in potentiometric titration of UO 2 2+ ion with Piroxycam.
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selective determination of trace copper ii by cathodic adsorptive stripping voltammetry with a Naphthol Derivative schiff s base
Annali Di Chimica, 2003Co-Authors: Mojtaba Shamsipur, Hashem Sharghi, Mahboubeh Saeidi, Hossein NaeimiAbstract:A selective and sensitive stripping voltammetric method for the determination of trace amounts of copper(II) with a recently synthesized Naphthol-Derivative Schiff's base (2,2'-[1,2-ethanediylbis(nitriloethylidyne)]bis(1-naphthalene)) is presented. The method is based on adsorptive accumulation of the resulting copper-Schiff's base complex on a hanging mercury drop electrode, followed by the stripping voltammetric measurement at the reduction current of adsorbed complex at -0.15 V (vs. Ag/AgCl). The optimal conditions for the stripping analysis of copper include pH 5.5 to 6.5, 8 microM Schiff's base and an accumulation potential of -0.05 V (vs. Ag/AgCI). The peak current is linearly proportional to the copper concentration over a range 2.3-50.8 ng ml(-1) with a limit of detection of 1.9 ng ml(-1). The accumulation time and RSD are 90 s and (3.2-3.5)%, respectively. The method was applied to the determination of copper in some analytical grade salts, tap water, human serum and sheep's liver.
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solid phase extraction of ultra trace copper ii using octadecyl silica membrane disks modified by a Naphthol Derivative schiff s base
Analytica Chimica Acta, 2000Co-Authors: Mojtaba Shamsipur, Hashem Sharghi, Alireza Ghiasvand, Hossein NaeimiAbstract:Abstract A simple and reliable method for the rapid extraction and determination of ultra trace amounts of copper(II) ions using octadecyl-bonded silica membrane disks modified by a recently synthesized Schiff’s base (2,2′-[1,2-ethanediyl bis(nitriloethylidyne)] bis(1-naphthalene)) and atomic absorption spectrometry is presented. Extraction efficiency and the influence pH, nature and amount of counter anion, flow rates and type of stripping acid were evaluated. The capacity of the membrane disks modified by 5 mg of the ligand was found to be 396 μg of copper. The limit of detection of the proposed method is 4 ng per 1000 ml. The method was applied to the extraction and recovery of copper in different water samples.
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copper ii selective membrane electrode based on a recently synthesized Naphthol Derivative schiff s base
Fresenius Journal of Analytical Chemistry, 1999Co-Authors: Naader Alizadeh, Hashem Sharghi, Hossein Naeimi, Sohrab Ershad, Mojtaba ShamsipurAbstract:A PVC membrane electrode for copper(II) ions based on a recently synthesized Naphthol-Derivative Schiff’s base as membrane carrier was prepared. The sensor exhibits a Nernstian response for Cu2+ ions over a wide concentration range (5.0 × 10–6–5.0 × 10–2 mol/L) with a detection limit of 3.1 × 10–6 mol/L (0.2 μg/mL). It has a very short response time of about 5 s and can be used for ¶3 months without any divergence in potential. The proposed electrode revealed good selectivities over a wide variety of other cations including alkali, alkaline earth, transition and heavy metal ions and could be used in a pH range of 4.0–7.0. It was successfully applied to the direct determination and potentiometric titration of copper ion.
Hashem Sharghi - One of the best experts on this subject based on the ideXlab platform.
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uo 2 2 ion selective membrane electrode based on a Naphthol Derivative schiff s base 2 2 1 2 ethandiyl bis nitriloethylidene bis 1 naphthalene
Bulletin of The Korean Chemical Society, 2004Co-Authors: Mojtaba Shamsipur, Hossein Naeimi, Mahboubeh Saeidi, Abdullah Yari, Ali Yaganehfaal, Mohammad Hossein Mashhadizadeh, Gholamhasan Azimi, Hashem SharghiAbstract:A new PVC membrane electrode for UO 2 2+ ion based on 2,2'-[1,2-ethanediyl bis (nitriloethylidene)]bis(1-naphthalene) as a suitable ionophore was prepared. The electrode exhibites a Nernstian response for UO 2 2+ ion over awide concentration range (1.0 x 10 - 1 -1.0 x 10 - 7 M) with a slope of 28.5 ′ 0.8 mV/decade. The limit of detection is 7.0 x 10 - 8 M. The electrode has a response time of < 20 s and a useful working pH range of 3-4. The proposed membrane sensor shows good discriminating abilities towards UO 2 2+ ion with regard to several alkali, alkaline earth transition and heavy metal ions. It was successfully used to the recovery of uranyl ion from, tap water and, as an indicator electrode, in potentiometric titration of UO 2 2+ ion with Piroxycam.
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selective determination of trace copper ii by cathodic adsorptive stripping voltammetry with a Naphthol Derivative schiff s base
Annali Di Chimica, 2003Co-Authors: Mojtaba Shamsipur, Hashem Sharghi, Mahboubeh Saeidi, Hossein NaeimiAbstract:A selective and sensitive stripping voltammetric method for the determination of trace amounts of copper(II) with a recently synthesized Naphthol-Derivative Schiff's base (2,2'-[1,2-ethanediylbis(nitriloethylidyne)]bis(1-naphthalene)) is presented. The method is based on adsorptive accumulation of the resulting copper-Schiff's base complex on a hanging mercury drop electrode, followed by the stripping voltammetric measurement at the reduction current of adsorbed complex at -0.15 V (vs. Ag/AgCl). The optimal conditions for the stripping analysis of copper include pH 5.5 to 6.5, 8 microM Schiff's base and an accumulation potential of -0.05 V (vs. Ag/AgCI). The peak current is linearly proportional to the copper concentration over a range 2.3-50.8 ng ml(-1) with a limit of detection of 1.9 ng ml(-1). The accumulation time and RSD are 90 s and (3.2-3.5)%, respectively. The method was applied to the determination of copper in some analytical grade salts, tap water, human serum and sheep's liver.
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solid phase extraction of ultra trace copper ii using octadecyl silica membrane disks modified by a Naphthol Derivative schiff s base
Analytica Chimica Acta, 2000Co-Authors: Mojtaba Shamsipur, Hashem Sharghi, Alireza Ghiasvand, Hossein NaeimiAbstract:Abstract A simple and reliable method for the rapid extraction and determination of ultra trace amounts of copper(II) ions using octadecyl-bonded silica membrane disks modified by a recently synthesized Schiff’s base (2,2′-[1,2-ethanediyl bis(nitriloethylidyne)] bis(1-naphthalene)) and atomic absorption spectrometry is presented. Extraction efficiency and the influence pH, nature and amount of counter anion, flow rates and type of stripping acid were evaluated. The capacity of the membrane disks modified by 5 mg of the ligand was found to be 396 μg of copper. The limit of detection of the proposed method is 4 ng per 1000 ml. The method was applied to the extraction and recovery of copper in different water samples.
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copper ii selective membrane electrode based on a recently synthesized Naphthol Derivative schiff s base
Fresenius Journal of Analytical Chemistry, 1999Co-Authors: Naader Alizadeh, Hashem Sharghi, Hossein Naeimi, Sohrab Ershad, Mojtaba ShamsipurAbstract:A PVC membrane electrode for copper(II) ions based on a recently synthesized Naphthol-Derivative Schiff’s base as membrane carrier was prepared. The sensor exhibits a Nernstian response for Cu2+ ions over a wide concentration range (5.0 × 10–6–5.0 × 10–2 mol/L) with a detection limit of 3.1 × 10–6 mol/L (0.2 μg/mL). It has a very short response time of about 5 s and can be used for ¶3 months without any divergence in potential. The proposed electrode revealed good selectivities over a wide variety of other cations including alkali, alkaline earth, transition and heavy metal ions and could be used in a pH range of 4.0–7.0. It was successfully applied to the direct determination and potentiometric titration of copper ion.
Molins Molina Óscar - One of the best experts on this subject based on the ideXlab platform.
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Unión fotoquímica irreversible de ligandos a albúminas séricas
'Universitat Politecnica de Valencia', 2020Co-Authors: Molins Molina ÓscarAbstract:[ES] En esta tesis se ha desarrollado una estrategia multidisciplinar que incluye la irradiación de complejos ligando/proteína junto con estudios de fluorescencia y/o espectroscopía de absorción transitoria, cromatografía de exclusión por tamaño seguida de espectroscopía de absorción y/o fluorescencia, análisis proteómico y modelización (docking y simulaciones de dinámica molecular) con el fin de profundizar y obtener información relevante en procesos relacionados con la formación de complejos irreversibles ligando-proteína. Ello ha permitido lograr la descripción del centro de reconocimiento molecular de albúminas séricas de distintas especies por el fármaco carprofeno, profundizar en procesos de fotoalergia producidos por el metabolito del fármaco triflusal y llevar a cabo el marcaje de residuos de lisina de la albúmina sérica humana por fotogeneración de electrófilos latentes "quinone methide". A continuación se describen brevemente cada uno de estos aspectos. En primer lugar, se ha estudiado la posible existencia de un centro de reconocimiento común en las albúminas séricas (AS) de diferentes especies empleando el fármaco antiinflamatorio no esteroideo (S)-carprofeno (CPF) como sonda fotoactiva. Así, se ha seguido la irradiación de los complejos de CPF/SA a ¿max = 320 nm por fluorescencia, mostrandose un aumento de la emisión debido a la deshalogenación. Tras la cromatografía de filtración en gel, la fracción proteica presentaba emisión proveniente del ligando, verificando la unión covalente del radical fotogenerado intermedio CBZ¿ a las AS. El análisis proteómico reveló la incorporación de CBZ¿ en varias posiciones en las diferentes albúminas. Se observaron modificaciones en la interfaz IB/IIIA en todos los casos (Tyr452 en las albúminas séricas humana, conejo y rata y Tyr451 en las albúminas séricas bovina, cerdo y oveja). Estudios de docking y de simulación de dinámica molecular el caso de albúmina sérica humana corroboraron las modificaciones covalentes observadas experimentalmente. Posteriormente, se ha investigado la unión fotoquímica del HTB, el metabolito del antiagregante plaquetario triflusal a albúmina sérica humana (ASH). El análisis proteómico de las disoluciones de HTB/ASH tras ser irradiadas mostró la adición de HTB en los grupos ¿-amino de los residuos Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 y Lys525 de la ASH. El mecanismo de reacción parece implicar la substitución del grupo CF3 del HTB por un nuevo residuo amida. Solo el residuo Lys199 se localiza en una cavidad interna de la proteína mientras que el resto de los residuos modificados resultaron estar situados en la parte externa. Los estudios computacionales revelaron que la unión supramolecular de HTB a ASH se produce en la región "V-cleft". Esta unión fotoquímica puede estar en la base de la aparición de efectos secundarios fotoalérgicos no deseados. Finalmente, se ha demostrado la utilidad de los 4-trifluorometilfenoles como pre-cursores de electrófilos latentes tipo "quinone methide" (QM) para la unión específica a residuos de lisina que se encuentran en los sitios de unión de la proteína. Así, se ha observado que estos aceptores de Michael, generados de modo fotoinducido, han sido capaces de realizar una modificación covalente específica de residuos de lisina en albúmina sérica humana (ASH). En concreto, los intermedios reactivos de tipo QM generados tras la irradiación de los complejos 4-trifluorometil-1-naftol o 4- (4-trifluorometilfenil) fenol con ASH exhibieron selectividad química hacia los residuos de lisina dando lugar a aductos de amida. Un estudio detallado realizado mediante análisis proteómico confirmó este hecho. Así, para el derivado de naftol se observó la modificación covalente de los residuos Lys106 y Lys414 (ubicados en los subdominios IA y IIIA, respectivamente), mientras que para el derivado de bife-nilol ocurrió la modificación[CAT] En aquesta tesi s'ha desenvolupat una estratègia multidisciplinària que inclou la irradiació de complexos lligand/proteïna juntament amb estudis de fluorescència i/o espectroscopia d'absorció de transients, cromatografia d'exclusió de grandària se-guida d'espectroscòpia d'absorció i/o fluorescència, anàlisi i modelització proteòmica (docking i simulacions de dinàmica molecular) amb l'objectiu d'aprofundir i obtenir informació rellevant en els processos relacionats amb la formació de com-plexos lligand-proteïna irreversibles. Això ha permès la descripció del centre de reconeixement molecular d'albúmines sèriques de diferents espècies pel fàrmac carprofen, i aprofundir en processos de fotoal·lèrgia produïts pel metabolit del fàrmac triflusal i realitzar el marcatge de residus de lisina d'albúmina sèrica humana per fotogeneració d'electròfil "quinone methide" latent. Cadascun d'aquests aspectes es descriu breument a continuació. En primer lloc, s'ha estudiat la possible existència d'un centre de reconeixement comú en albúmines sèriques (AS) de diferents espècies utilitzant el fàrmac antiinflamatori no esteroïdal (S)-carprofèn (CPF) com a sonda fotoactiva. Així, s'ha se-guit la irradiació dels complexos de CPF/SA a un màxim de 320 nm per fluorescència, amb un augment de les emissions a causa de la deshalogenació. Després de la cromatografia de filtració de gel, la fracció de proteïna presentava emissió del lli-gand, verificant la unió covalent del radical fotogenerat intermedi CBZ¿ a les AS. L'anàlisi proteòmica va revelar la incorporació de CBZ¿ en diverses posicions en els diferents albúmines. En tots els casos s'han observat modificacions a la interfície IB/IIIA (Tyr452 en albúmina sèrica humana, conill i rata i Tyr451 en albúmines sèriques bovina, porc i ovella). Els estudis de docking i de simulació de dinàmiques moleculars en el cas d'albúmina sèrica humana van corroborar les modificacions covalents experimentalment observades. Posteriorment, s'ha investigat la unió fotoquímica del HTB, el metabòlit de l'antiagregant plaquetari triflusal a l'albúmina sèrica humana (ASH). L'anàlisi proteòmica de les solucions HTB/ASH després de ser irradiades mostraren l'addició de HTB en els grups ¿-amino dels residus Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 i Lys525 de la ASH . El mecanisme de reacció podria implicar la substitució del grup CF3 de la HTB amb un nou residu d'amida. Només el residu Lys199 està situat en una cavitat interna de la proteïna, mentre que la resta dels residus modificats van resultar estar situats a l'exterior. Els estudis computacionals van revelar que la unió supramolecular de HTB a ASH es produeix a la regió "V-cleft". Aquesta unió fotoquímica pot ser la base de l'aparició d'efectes secundaris fotoal·lèrgics no desitjats. Finalment, s'ha demostrat la utilitat de 4-trifluorometilfenols com a precursors d'electròfils latents "quinone methide" (QM) per a la unió específica a residus de lisina trobats en els llocs d'unió de la proteïna. Per tant, s'ha observat que els acceptors de Michael, generats de manera foto-induïda han pogut fer una modificació covalent específica de residus de lisina en albúmina de sèrica humana (ASH). Concretament, els intermedis reactius del tipus QM generats després de la irradiació dels complexos 4-trifluoromethyl-1-naftol o 4-(4-trifluoromethylphenyl) fenol amb ASH exhibiren selectivitat química als residus de lisina resultant en aductes ami-da. Un estudi detallat realitzat mitjançant anàlisi proteòmica confirmà aquest fet. Així, pel derivat del naftol, es va observar la modificació covalents de residus Lys106 i Lys414 (localitzada en subdominis IA i IIIA, respectivament), mentre que per al derivat de bifenil la modificació es va produir en el Lys195 (en subdomini IIA). Els estudis teòrics proporcionen una visió molecular més profunda de la selectivitat observada[EN] In this thesis a multidisciplinary strategy has been developed that includes irradiation of ligand/protein complexes along with fluorescence and/or transient absorption spectroscopy, size-exclusion chromatography followed by absorption and/or fluorescence spectroscopy, proteomic analysis and modelling (docking and molecular dynamics simulations) in order to deepen and obtain relevant information in processes related to the formation of irreversible ligand-protein complexes. This has made it possible to achieve the description of the molecular recognition centre of serum albumin of different species by the carprofen drug, to deepen in photoallergy processes produced by the metabolite of the triflusal drug and to carry out the la-belling of lysine residues of human serum albumin by photogeneration of latent electrophiles "quinone methide". Each of these aspects is briefly described below. First, the possible existence of a common recognition centre in serum albumin (SA) of different species has been studied using the non-steroidal antiinflammatory drug (S)-carprofen (CPF) as a photoactive probe. Thus, irradiation of the CPF/SA complexes at ¿max = 320 nm has been followed by fluorescence, showing an increase in emission due to dehalogenation. After gel filtration chromatography, the protein fraction presented emission from the ligand, verifying the covalent bonding of the CBZ¿ intermediate photogenerated radical to the SA. Proteomic analysis revealed the incorporation of CBZ¿ in various positions in the different albumins. Modifications in the IB/IIIA interface were observed in all cases (Tyr452 in human, rabbit and rat serum albumin and Tyr451 in bovine, porcine and sheep serum albumin). Docking and molecular dynamics simulation studies in the case of human serum albumin corroborated the experimentally observed covalent modifications. Subsequently, the photochemical binding of HTB, the metabolite of the triflusal platelet antiaggregant to human serum albumin (HSA), has been investigated. Proteomic analysis of the HTB/HSA solutions after being irradiated showed the addition of HTB in the ¿-amino groups of residues Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 and Lys525 of the HSA. The reaction mechanism seems to involve replacing the CF3 group of HTB with a new amide residue. Only the Lys199 residue is located in an internal cavity of the protein whilst the rest of the modified residues were found to be located on the outside. Computational studies revealed that supramolecular binding of HTB to HSA occurs in the "V-cleft" region. This photochemical binding may be at the base of the appearance of unwanted photoallergic side effects. Finally, the utility of 4-trifluoromethylphenols as precursors of latent "quinone methide" (QM) type electrophiles for specific binding to lysine residues found at the protein binding sites has been demonstrated. Thus, it has been observed that these photogenerated Michael acceptors, have been able to perform a specific covalent modification of lysine residues in human serum albumin (HSA). Specifically, the QM type reactive intermediates generated after irradiation of the 4-trifluoromethyl-1-Naphthol or 4- (4-trifluoromethylphenyl) phenol complexes with HSA exhibited chemical selectivity towards lysine residues giving rise to amide adducts. A detailed study conducted by proteomic analysis confirmed this fact. Thus, for the Naphthol Derivative the covalent modification of residues Lys106 and Lys414 (located in subdomains IA and IIIA, respectively) was observed, while for the biphenyl Derivative the modification occurred in Lys195 (in subdomain IIA). Theoretical studies provided a deeper insight at the molecular level of the experimentally observed selectivity.Molins Molina, Ó. (2020). Unión fotoquímica irreversible de ligandos a albúminas séricas [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/139676TESI
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Unión fotoquímica irreversible de ligandos a albúminas séricas
'Universitat Politecnica de Valencia', 2020Co-Authors: Molins Molina ÓscarAbstract:Tesis por compendio[ES] En esta tesis se ha desarrollado una estrategia multidisciplinar que incluye la irradiación de complejos ligando/proteína junto con estudios de fluorescencia y/o espectroscopía de absorción transitoria, cromatografía de exclusión por tamaño seguida de espectroscopía de absorción y/o fluorescencia, análisis proteómico y modelización (docking y simulaciones de dinámica molecular) con el fin de profundizar y obtener información relevante en procesos relacionados con la formación de complejos irreversibles ligando-proteína. Ello ha permitido lograr la descripción del centro de reconocimiento molecular de albúminas séricas de distintas especies por el fármaco carprofeno, profundizar en procesos de fotoalergia producidos por el metabolito del fármaco triflusal y llevar a cabo el marcaje de residuos de lisina de la albúmina sérica humana por fotogeneración de electrófilos latentes "quinone methide". A continuación se describen brevemente cada uno de estos aspectos. En primer lugar, se ha estudiado la posible existencia de un centro de reconocimiento común en las albúminas séricas (AS) de diferentes especies empleando el fármaco antiinflamatorio no esteroideo (S)-carprofeno (CPF) como sonda fotoactiva. Así, se ha seguido la irradiación de los complejos de CPF/SA a ¿max = 320 nm por fluorescencia, mostrandose un aumento de la emisión debido a la deshalogenación. Tras la cromatografía de filtración en gel, la fracción proteica presentaba emisión proveniente del ligando, verificando la unión covalente del radical fotogenerado intermedio CBZ¿ a las AS. El análisis proteómico reveló la incorporación de CBZ¿ en varias posiciones en las diferentes albúminas. Se observaron modificaciones en la interfaz IB/IIIA en todos los casos (Tyr452 en las albúminas séricas humana, conejo y rata y Tyr451 en las albúminas séricas bovina, cerdo y oveja). Estudios de docking y de simulación de dinámica molecular el caso de albúmina sérica humana corroboraron las modificaciones covalentes observadas experimentalmente. Posteriormente, se ha investigado la unión fotoquímica del HTB, el metabolito del antiagregante plaquetario triflusal a albúmina sérica humana (ASH). El análisis proteómico de las disoluciones de HTB/ASH tras ser irradiadas mostró la adición de HTB en los grupos ¿-amino de los residuos Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 y Lys525 de la ASH. El mecanismo de reacción parece implicar la substitución del grupo CF3 del HTB por un nuevo residuo amida. Solo el residuo Lys199 se localiza en una cavidad interna de la proteína mientras que el resto de los residuos modificados resultaron estar situados en la parte externa. Los estudios computacionales revelaron que la unión supramolecular de HTB a ASH se produce en la región "V-cleft". Esta unión fotoquímica puede estar en la base de la aparición de efectos secundarios fotoalérgicos no deseados. Finalmente, se ha demostrado la utilidad de los 4-trifluorometilfenoles como pre-cursores de electrófilos latentes tipo "quinone methide" (QM) para la unión específica a residuos de lisina que se encuentran en los sitios de unión de la proteína. Así, se ha observado que estos aceptores de Michael, generados de modo fotoinducido, han sido capaces de realizar una modificación covalente específica de residuos de lisina en albúmina sérica humana (ASH). En concreto, los intermedios reactivos de tipo QM generados tras la irradiación de los complejos 4-trifluorometil-1-naftol o 4- (4-trifluorometilfenil) fenol con ASH exhibieron selectividad química hacia los residuos de lisina dando lugar a aductos de amida. Un estudio detallado realizado mediante análisis proteómico confirmó este hecho. Así, para el derivado de naftol se observó la modificación covalente de los residuos Lys106 y Lys414 (ubicados en los subdominios IA y IIIA, respectivamente), mientras que para el derivado de bife-nilol ocurrió la modificación[CA] En aquesta tesi s'ha desenvolupat una estratègia multidisciplinària que inclou la irradiació de complexos lligand/proteïna juntament amb estudis de fluorescència i/o espectroscopia d'absorció de transients, cromatografia d'exclusió de grandària se-guida d'espectroscòpia d'absorció i/o fluorescència, anàlisi i modelització proteòmica (docking i simulacions de dinàmica molecular) amb l'objectiu d'aprofundir i obtenir informació rellevant en els processos relacionats amb la formació de com-plexos lligand-proteïna irreversibles. Això ha permès la descripció del centre de reconeixement molecular d'albúmines sèriques de diferents espècies pel fàrmac carprofen, i aprofundir en processos de fotoal·lèrgia produïts pel metabolit del fàrmac triflusal i realitzar el marcatge de residus de lisina d'albúmina sèrica humana per fotogeneració d'electròfil "quinone methide" latent. Cadascun d'aquests aspectes es descriu breument a continuació. En primer lloc, s'ha estudiat la possible existència d'un centre de reconeixement comú en albúmines sèriques (AS) de diferents espècies utilitzant el fàrmac antiinflamatori no esteroïdal (S)-carprofèn (CPF) com a sonda fotoactiva. Així, s'ha se-guit la irradiació dels complexos de CPF/SA a un màxim de 320 nm per fluorescència, amb un augment de les emissions a causa de la deshalogenació. Després de la cromatografia de filtració de gel, la fracció de proteïna presentava emissió del lli-gand, verificant la unió covalent del radical fotogenerat intermedi CBZ¿ a les AS. L'anàlisi proteòmica va revelar la incorporació de CBZ¿ en diverses posicions en els diferents albúmines. En tots els casos s'han observat modificacions a la interfície IB/IIIA (Tyr452 en albúmina sèrica humana, conill i rata i Tyr451 en albúmines sèriques bovina, porc i ovella). Els estudis de docking i de simulació de dinàmiques moleculars en el cas d'albúmina sèrica humana van corroborar les modificacions covalents experimentalment observades. Posteriorment, s'ha investigat la unió fotoquímica del HTB, el metabòlit de l'antiagregant plaquetari triflusal a l'albúmina sèrica humana (ASH). L'anàlisi proteòmica de les solucions HTB/ASH després de ser irradiades mostraren l'addició de HTB en els grups ¿-amino dels residus Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 i Lys525 de la ASH . El mecanisme de reacció podria implicar la substitució del grup CF3 de la HTB amb un nou residu d'amida. Només el residu Lys199 està situat en una cavitat interna de la proteïna, mentre que la resta dels residus modificats van resultar estar situats a l'exterior. Els estudis computacionals van revelar que la unió supramolecular de HTB a ASH es produeix a la regió "V-cleft". Aquesta unió fotoquímica pot ser la base de l'aparició d'efectes secundaris fotoal·lèrgics no desitjats. Finalment, s'ha demostrat la utilitat de 4-trifluorometilfenols com a precursors d'electròfils latents "quinone methide" (QM) per a la unió específica a residus de lisina trobats en els llocs d'unió de la proteïna. Per tant, s'ha observat que els acceptors de Michael, generats de manera foto-induïda han pogut fer una modificació covalent específica de residus de lisina en albúmina de sèrica humana (ASH). Concretament, els intermedis reactius del tipus QM generats després de la irradiació dels complexos 4-trifluoromethyl-1-naftol o 4-(4-trifluoromethylphenyl) fenol amb ASH exhibiren selectivitat química als residus de lisina resultant en aductes ami-da. Un estudi detallat realitzat mitjançant anàlisi proteòmica confirmà aquest fet. Així, pel derivat del naftol, es va observar la modificació covalents de residus Lys106 i Lys414 (localitzada en subdominis IA i IIIA, respectivament), mentre que per al derivat de bifenil la modificació es va produir en el Lys195 (en subdomini IIA). Els estudis teòrics proporcionen una visió molecular més profunda de la selectivitat observada[EN] In this thesis a multidisciplinary strategy has been developed that includes irradiation of ligand/protein complexes along with fluorescence and/or transient absorption spectroscopy, size-exclusion chromatography followed by absorption and/or fluorescence spectroscopy, proteomic analysis and modelling (docking and molecular dynamics simulations) in order to deepen and obtain relevant information in processes related to the formation of irreversible ligand-protein complexes. This has made it possible to achieve the description of the molecular recognition centre of serum albumin of different species by the carprofen drug, to deepen in photoallergy processes produced by the metabolite of the triflusal drug and to carry out the la-belling of lysine residues of human serum albumin by photogeneration of latent electrophiles "quinone methide". Each of these aspects is briefly described below. First, the possible existence of a common recognition centre in serum albumin (SA) of different species has been studied using the non-steroidal antiinflammatory drug (S)-carprofen (CPF) as a photoactive probe. Thus, irradiation of the CPF/SA complexes at ¿max = 320 nm has been followed by fluorescence, showing an increase in emission due to dehalogenation. After gel filtration chromatography, the protein fraction presented emission from the ligand, verifying the covalent bonding of the CBZ¿ intermediate photogenerated radical to the SA. Proteomic analysis revealed the incorporation of CBZ¿ in various positions in the different albumins. Modifications in the IB/IIIA interface were observed in all cases (Tyr452 in human, rabbit and rat serum albumin and Tyr451 in bovine, porcine and sheep serum albumin). Docking and molecular dynamics simulation studies in the case of human serum albumin corroborated the experimentally observed covalent modifications. Subsequently, the photochemical binding of HTB, the metabolite of the triflusal platelet antiaggregant to human serum albumin (HSA), has been investigated. Proteomic analysis of the HTB/HSA solutions after being irradiated showed the addition of HTB in the ¿-amino groups of residues Lys137, Lys199, Lys205, Lys352, Lys432, Lys541, Lys545 and Lys525 of the HSA. The reaction mechanism seems to involve replacing the CF3 group of HTB with a new amide residue. Only the Lys199 residue is located in an internal cavity of the protein whilst the rest of the modified residues were found to be located on the outside. Computational studies revealed that supramolecular binding of HTB to HSA occurs in the "V-cleft" region. This photochemical binding may be at the base of the appearance of unwanted photoallergic side effects. Finally, the utility of 4-trifluoromethylphenols as precursors of latent "quinone methide" (QM) type electrophiles for specific binding to lysine residues found at the protein binding sites has been demonstrated. Thus, it has been observed that these photogenerated Michael acceptors, have been able to perform a specific covalent modification of lysine residues in human serum albumin (HSA). Specifically, the QM type reactive intermediates generated after irradiation of the 4-trifluoromethyl-1-Naphthol or 4- (4-trifluoromethylphenyl) phenol complexes with HSA exhibited chemical selectivity towards lysine residues giving rise to amide adducts. A detailed study conducted by proteomic analysis confirmed this fact. Thus, for the Naphthol Derivative the covalent modification of residues Lys106 and Lys414 (located in subdomains IA and IIIA, respectively) was observed, while for the biphenyl Derivative the modification occurred in Lys195 (in subdomain IIA). Theoretical studies provided a deeper insight at the molecular level of the experimentally observed selectivity.Molins Molina, Ó. (2020). Unión fotoquímica irreversible de ligandos a albúminas séricas [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/139676TESISCompendi
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single step synthesis of a radically polymerizable 1 1 bi 2 Naphthol Derivative for asymmetric catalysis
Polymer International, 2015Co-Authors: Carolin Fleischmann, Helmut RitterAbstract:A new polymerizable 1,1′-bi-2-Naphthol Derivative for polymer-supported catalytic asymmetric synthesis is presented. The synthesis is conducted within a single reaction step, which is a major advantage over other approaches presented in the literature. The ligand-bearing polymer is prepared through copolymerization with N-isopropylacrylamide. Preliminary experiments on the utility in catalytic asymmetric alkylation reactions reveal the accessibility and activity of the polymer-attached catalysts. The stereoselectivity of the reaction is found to be somewhat lower than for reactions performed in the presence of free 1,1′-bi-2-Naphthol, and thus requires further optimization. The enantiomeric excess of the reaction products was determined via 1H NMR spectroscopy after chiral derivatization with (R)-α-methylbenzyl isocyanate. © 2015 Society of Chemical Industry
