Title Sinteza BODIPY spojeva koji ciljaju unutarstanične organele
Title (english) Synthesis of BODIPY compounds that target intracellular organelles
Author Lorena Vidoša
Mentor Nikola Basarić (mentor)
Mentor Nela Malatesti (komentor)
Committee member Nikola Basarić (predsjednik povjerenstva)
Committee member Nela Malatesti (član povjerenstva)
Committee member Miranda Mladinić Pejatović (član povjerenstva)
Committee member Jurica Novak (član povjerenstva)
Committee member Duško Čakara (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2023-09-12, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Abstract Fluorescentna mikroskopija je moćna tehnika slikovnog prikazivanja
koja se koristi u različitim znanstvenim područjima, posebno u biologiji i
medicini, kako bi se vizualiziralo i proučavalo raspodjelu i ponašanje molekula
unutar stanica i tkiva. Koristi se fenomenom fluorescencije, koji omogućuju
različiti fluorofori ili fluorescentne boje. Kao dio ovog rada, sintetizirane su
dvije nove fluorescentne BODIPY boje koje sadrže supstituente na mesopoložaju, koji su posebno dizajnirani da ciljaju lizosome ili endoplazmatski
retikulum (ER). Sama sintetetska strategija temeljila se na pripremi BODIPY
karboksilne kiseline, koja je metodom peptidne sinteze u izvrsnim prinosima
vezana za derivate morfolina ili tosilsulfonamida. Pokušaji sinteze BODIPY
derivata s trifenilfosfonijevom soli koja bi ciljala mitohondrije nisu uspjeli zbog
neuspješne Williamsove sinteze etera BODIPY fenola s bromoalkinom.
Spektralna i fotofizička svojstva istražena su u nepolarnim (CH2Cl2), polarnim
otapalima - aprotičnim (CH3CN) i protičnim (H2O). Spojevi imaju usku i
snažnu apsorpcijsku (≈ 498 nm) i emisijsku vrpcu (510-515 nm) u vidljivom
području te male Stokesove pomake. Spojevi ne pokazuju fluorosolvatokromna svojstva, ali kvantni prinosi fluorescencije (Φf = 0,50-0,75)
opadaju s povećanjem polarnosti otapala. Vremena života singletnih
pobuđenih stanja izmjerena su metodom vremenski koreliranog brojanja
pojedinačnih fotona i nalaze se u rasponu nekoliko nanosekundi (τ = 2,6-3,0
ns). Eksperimenti fluorescentne mikroskopije izvedeni su na staničnoj liniji
HFF, a pokazuju laku internalizaciju spojeva i specifično bojenje lizosoma ili
ER-a pri koncentracijama od 5 μM, odnosno 1 μM. Dobiveni rezultati sugeriraju
moguću primjenu novosintetiziranih BODIPY spojeva u medicini i biologiji kao
fluorescentnih indikatora za ciljanje lizosoma i ER-a.
Abstract (english) Fluorescence microscopy is a powerful imaging technique used in
various scientific fields, particularly in biology and medicine, to visualize and
study the distribution and behavior of molecules within cells and tissues. It
exploits the phenomenon of fluorescence, which is attributed to various
fluorophores or fluorescent dyes. As a part of this thesis, two new fluorescent
BODIPY dyes were synthesized, containing substituents at the meso-position,
specifically designed to target lysosomes or endoplasmic reticulum (ER). The
synthetic strategy was based on the preparation of a BODIPY carboxylic acid,
which was in the peptide coupling protocol in excellent yields attached to a
morpholine residue or tosylsulphonamide derivative, respectively. Attempted
synthesis of a BODIPY derivative with triphenylphosphonium salt to target
mitochondria failed due to unsuccessful Williams ether synthesis of a BODIPY
phenol with a bromoalkyne derivative. Spectral and photophysical properties
were investigated in nonpolar (CH2Cl2), polar solvents – aprotic (CH3CN) and
protic (H2O). The compounds have narrow and strong absorption (≈ 498 nm)
and emission bands (510-515 nm) in the visible region and have small Stokes
shifts. The compounds do not exhibit fluoro-solvatochromic properties, but the
quantum yields of fluorescence (Φf = 0.50-0.75) decrease with increasing
solvent polarity. Singlet excited state lifetimes were measured by timecorrelated single photon counting and they are in the nanosecond time-scale
(τ = 2.6-3.0 ns). The fluorescence microscopy experiments were performed
on the HFF cell line, demonstrating the easy internalization of the compounds
and specific staining of lysosomes or ER at concentrations 5 μM and 1 μM,
respectively. The obtained results suggest a potential application of the newly
synthesized BODIPY compounds in medicine and biology as fluorescent
indicators for targeting lysosomes and ER.
Keywords
BODIPY
endoplazmatski retikulum
fluorescencijska mikroskopija
fotofizika
lizosomi
mitohondrij
organska sinteza
Keywords (english)
BODIPY
fluorescence microscopy
endoplasmic reticulum
lysosomes
mitochondria
organic synthesis
photophysics
Language croatian
URN:NBN urn:nbn:hr:193:408694
Study programme Title: Drug research and development Study programme type: university Study level: graduate Academic / professional title: magistar/magistra istraživanja i razvoja lijekova (magistar/magistra istraživanja i razvoja lijekova)
Type of resource Text
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Access conditions Open access
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Created on 2023-10-11 11:38:22