Among the extensive family of supramolecular compounds, porous crystalline materials present appealing features: permanent porosity, good thermal and chemical stability, versatile functionalization, long-range order properties and multiple application branches. One of the latter is nanomedicine, which can spread from drug storage and delivery to enantioselective separation of pharmaceutical precursors. In my phD work I focused on two classes of crystalline microporous materials and their adsorption and enantioselective uptake properties. The porous dipeptides belonging to the Valyl-Alanine family result to be low density materials, with stable porosity and 1D chiral and hydrophobic channels. Five porous dipeptide matrixes, Valyl-Alanine, Alanyl-Isoleucine, Valyl-Valine, Isoleucyl-Alanine and Isoleucyl-Valine, were tested for the adsorption of volatile halogenated ethers used in general anesthesia, namely enflurane, isoflurane, halothane, desflurane and the common diethyl ether. Adsorption and desorption isotherms were performed at 273 and 298 K, showing the great affinity of the first three matrixes for the halogenated guests. The anesthetic molecules included in the dipeptide crystals were detected by 13C, 19F and fast- 1H MAS NMR spectroscopy. A conformational analysis on isoflurane and enflurane was conducted to determine the most stable energy minima and to simulate the relative NMR spectra, to be compared with the experimental ones. In the second part of the thesis, four new metal-organic frameworks (MOFs), characterized by alkyl moieties with enantiopure stereogenic centers lined inside the channels, are presented. The reaction between Cu(II) cations and organic tectons with methyl or hydroxyl groups bonded to the stereogenic carbons give tridimensional, stable and microporous structures, 1-Cu, 3-Cu, 1-Cu(OH) and 3-Cu(OH), respectively. First, the porosity of the homo-chiral MOFs was confirmed by N2 and CO2 adsorption isotherms. Then, the chiral and porous nature of these MOFs was explored for enantioselective uptake experiments. The first frameworks, 1-Cu and 3-Cu, thanks to their stability in water, were exploited for the adsorption in solution of the two enantiomers of tryptophan, monitored by UV-vis spectroscopy for 24 hours. The other two matrixes, 1-Cu(OH) and 3-Cu(OH), were employed for the resolution of racemic amines and amides by HPLC. After the soaking, the MOFs were carefully washed and on the remaining solutions a derivatization reaction was performed, in order to get aromatic compounds detectable by the UV-vis analyzer of the HPLC system. In conclusion, the first two MOFs showed a good selectivity, with 3-Cu preferentially adsorbing L-tryptophan in a ratio 3.3:1 compared to the D-isomer after just 30 minutes, while 1-Cu(OH) and 3-Cu(OH) presented negligible enantiomeric excess values.

La mia tesi tratta di materiali cristallini microporosi e delle loro proprietà di adsorbimento di gas e liquidi. Mi sono occupata di cristalli dipeptidici e di metal-organic frameworks. Innanzittutto, ho analizzato i Valil-Alanina, Alanil-Isoleucina, Valil-Valina, Alanil-Isoleucina e Isoleucil-Valina e ho testato le loro capacità di assorbimento di anestetici volatili. Sono state condotte isoterme di adsorbimento di enflurano, isoflurano, alotano, desflurano e dietiletere a 298 e a 273 K. VA, VV e AI presentano un’affinità elevata per i guests, rappresentata da calori isosterici superiori a 30 kJ/mol e quantità assorbite fino a 20 cm3/g. Invece, IA e IV si sono dimostrate inefficaci, a causa delle ristrette dimensioni dei loro canali. Sono stati realizzati esperimenti nmr allo stato solido per i nuclei 13C, 1H e 19F. Gli spettri 1H a 30 kHz mostrano due tipologie di segnali: a ppm più bassi quelli dei guest assorbiti nelle matrici, mentre a ppm più elevati quelli dei guest presenti solo sulla superficie esterna, a dimostrazione del riempimento completo dei canali. I pattern di diffrazione confermano inoltre la stabilità dei dipeptidi anche in presenza di guests. Successivamente, si è proceduto con l’ottimizzazione dei minimi conformazionali di enflurano e isoflurano, di cui sono stati simulati i relativi spettri nmr. Dal confronto tra gli spettri simulati e quelli sperimentali è risultato che l’isoflurano viene assorbito nella VA in una sola delle sue due conformazioni. Il passo successivo è stata l’indagine delle proprietà di enantioselettività di metal-organic frameworks omochirali. Sono stati studiati quattro MOFs a base di Cu(ll), caratterizzati dallo stesso legante organico tetracarbossilato, a cui sono attaccate catene contenenti differenti centri chirali, direzionati all’interno dei nanocanali. Dei primi due MOFs, 1-Cu e 3-Cu, immersi in soluzioni acquose enantiopure di triptofano, è stato monitorato l’assorbimento dei due enantiomeri nel tempo tramite spettroscopia UV-visibile. Il reticolo 3-Cu possiede una buona selettività, preferendo l’L-triptofano all’enantiomero D in rapporto superiore a 3.3:1 dopo trenta minuti. Gli altri due MOFs, caratterizzati da gruppi ossidrilici legati allo stereocentro, sono stati studiati per la separazione di miscele racemiche. La sec-butilammina, l’etilbenzilammina e la sec-benzamide, precursori farmaceutici, sono stati fatti assorbire in soluzione in presenza dei MOFs e i prodotti benzoilati derivanti dall’assorbimento sono stati analizzati tramite HPLC. I cromatogrammi presentano picchi completamente risolti e brevi tempi di analisi. I bassi valori di enantioselettività sono dovuti in un caso alle ridotte dimensioni della butiliammina, e nell’altro alla scarsa affinità dei MOFs per le molecole aromatiche. Nonostante ciò, questi MOFs potrebbero risultare efficaci nella separazione di molecole alifatiche a lunga catena.

(2018). Supramolecular porous crystals: anesthetic vapors uptake and enantioselective recognition properties. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2018).

Supramolecular porous crystals: anesthetic vapors uptake and enantioselective recognition properties

ASNAGHI, DONATA
2018

Abstract

Among the extensive family of supramolecular compounds, porous crystalline materials present appealing features: permanent porosity, good thermal and chemical stability, versatile functionalization, long-range order properties and multiple application branches. One of the latter is nanomedicine, which can spread from drug storage and delivery to enantioselective separation of pharmaceutical precursors. In my phD work I focused on two classes of crystalline microporous materials and their adsorption and enantioselective uptake properties. The porous dipeptides belonging to the Valyl-Alanine family result to be low density materials, with stable porosity and 1D chiral and hydrophobic channels. Five porous dipeptide matrixes, Valyl-Alanine, Alanyl-Isoleucine, Valyl-Valine, Isoleucyl-Alanine and Isoleucyl-Valine, were tested for the adsorption of volatile halogenated ethers used in general anesthesia, namely enflurane, isoflurane, halothane, desflurane and the common diethyl ether. Adsorption and desorption isotherms were performed at 273 and 298 K, showing the great affinity of the first three matrixes for the halogenated guests. The anesthetic molecules included in the dipeptide crystals were detected by 13C, 19F and fast- 1H MAS NMR spectroscopy. A conformational analysis on isoflurane and enflurane was conducted to determine the most stable energy minima and to simulate the relative NMR spectra, to be compared with the experimental ones. In the second part of the thesis, four new metal-organic frameworks (MOFs), characterized by alkyl moieties with enantiopure stereogenic centers lined inside the channels, are presented. The reaction between Cu(II) cations and organic tectons with methyl or hydroxyl groups bonded to the stereogenic carbons give tridimensional, stable and microporous structures, 1-Cu, 3-Cu, 1-Cu(OH) and 3-Cu(OH), respectively. First, the porosity of the homo-chiral MOFs was confirmed by N2 and CO2 adsorption isotherms. Then, the chiral and porous nature of these MOFs was explored for enantioselective uptake experiments. The first frameworks, 1-Cu and 3-Cu, thanks to their stability in water, were exploited for the adsorption in solution of the two enantiomers of tryptophan, monitored by UV-vis spectroscopy for 24 hours. The other two matrixes, 1-Cu(OH) and 3-Cu(OH), were employed for the resolution of racemic amines and amides by HPLC. After the soaking, the MOFs were carefully washed and on the remaining solutions a derivatization reaction was performed, in order to get aromatic compounds detectable by the UV-vis analyzer of the HPLC system. In conclusion, the first two MOFs showed a good selectivity, with 3-Cu preferentially adsorbing L-tryptophan in a ratio 3.3:1 compared to the D-isomer after just 30 minutes, while 1-Cu(OH) and 3-Cu(OH) presented negligible enantiomeric excess values.
SOZZANI, PIERO ERNESTO
porous; materials,; gas,; adsorption,; enantioselectivity
porous; materials,; gas,; adsorption,; enantioselectivity
CHIM/04 - CHIMICA INDUSTRIALE
English
20-mar-2018
SCIENZA E NANOTECNOLOGIA DEI MATERIALI - 79R
30
2016/2017
open
(2018). Supramolecular porous crystals: anesthetic vapors uptake and enantioselective recognition properties. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2018).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/199107
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