Photochemical decarboxylation of phthalimide derivatives

U okviru ove doktorske disertacije provedena je sinteza novih derivata ftalimida i istraživanje fotokemijske reaktivnosti tih spojeva. Novopripravljene molekule su ftalimidni derivati adamantanskih aminokiselina, pri čemu je istražen utjecaj udaljenosti između ftalimidnog kromofora (akceptor elektrona) i karboksilne skupine (donor elektrona) na učinkovitost fotoinduciranog prijenosa elektrona (PET) i dekarboksilacije. Udaljenost tih skupina ima značajan utjecaj na učinkovitost dekarboksilacije istraživanih spojeva, a intramolekulski PET je najsporiji stupanj cijelog procesa. Nadalje, istražen je i utjecaj različitih supstituenata vezanih na položaju 4 ftalimidnog kromofora na fotofizička svojstva i fotokemijsku reaktivnost. Ftalimide s elektron-donorskim supstituentom općenito karakterizira reaktivnost i iz singletnog i iz tripletnog pobuđenog stanja. Fluorescencija tih spojeva je u kompeticiji s PET-om, a populacija tripletnog pobuđenog stanja u odsutnosti senzibilizatora je neučinkovita. S druge strane, ftalimidi s elektron-akceptorskim supstituentom reagiraju uglavnom iz tripletnog pobuđenog stanja. Međutim, nitro-derivat je drukčiji budući da ima reaktivnost karakterističnu za nitrobenzenski kromofor. Istraživan je i utjecaj supramolekulske kontrole s ciklodekstrinima (CD) na [3 + 2] cikloadiciju alkena i fotogeneriranih azometin-ilida iz odabranih ftalimida. Kompleksiranjem adamantilftalimidnog derivata s β-CD povećava se iskorištenje adukata.In this PhD thesis synthesis of new phthalimide derivatives and study of their photochemical reactivity are described. Newly synthesized molecules are phthalimide derivatives of adamantane amino acids, where an influence of the distance between the phthalimide (electron acceptor) and the carboxylate (electron donor) on photoinduced electron transfer (PET) and decarboxylation efficiency was investigated. The distance between these groups in the investigated compounds has a significant influence on the decarboxylation efficiency, while PET is the rate-determining step of the whole process. Moreover, study of the influence of different substituents attached to the position 4 of the phthalimide chromophore on the photophysical properties and photochemical reactivity was conducted. The phthalimides bearing electron-donating substituents are generally characterized by reactivity from both singlet and triplet excited states. The fluorescence from these compounds is in competition with PET, and triplet excited state population in the absence of a sensitizer is inefficient. On the contrary, phthalimides bearing electron-withdrawing substituents react mostly from the triplet excited state. However, the nitro derivative is different since it exhibits typical reactivity of the nitrobenzene chromophore. The effect of supramolecular control with cyclodextrins (CD) on [3 + 2] cycloaddition of alkenes and photogenerated azomethine ylides from selected phthalimides was described. Complexation of adamantylphthalimide derivative with β-CD increased the yield of adducts

Photochemical decarboxylation of phthalimide derivatives

U okviru ove doktorske disertacije provedena je sinteza novih derivata ftalimida i istraživanje fotokemijske reaktivnosti tih spojeva. Novopripravljene molekule su ftalimidni derivati adamantanskih aminokiselina, pri čemu je istražen utjecaj udaljenosti između ftalimidnog kromofora (akceptor elektrona) i karboksilne skupine (donor elektrona) na učinkovitost fotoinduciranog prijenosa elektrona (PET) i dekarboksilacije. Udaljenost tih skupina ima značajan utjecaj na učinkovitost dekarboksilacije istraživanih spojeva, a intramolekulski PET je najsporiji stupanj cijelog procesa. Nadalje, istražen je i utjecaj različitih supstituenata vezanih na položaju 4 ftalimidnog kromofora na fotofizička svojstva i fotokemijsku reaktivnost. Ftalimide s elektron-donorskim supstituentom općenito karakterizira reaktivnost i iz singletnog i iz tripletnog pobuđenog stanja. Fluorescencija tih spojeva je u kompeticiji s PET-om, a populacija tripletnog pobuđenog stanja u odsutnosti senzibilizatora je neučinkovita. S druge strane, ftalimidi s elektron-akceptorskim supstituentom reagiraju uglavnom iz tripletnog pobuđenog stanja. Međutim, nitro-derivat je drukčiji budući da ima reaktivnost karakterističnu za nitrobenzenski kromofor. Istraživan je i utjecaj supramolekulske kontrole s ciklodekstrinima (CD) na [3 + 2] cikloadiciju alkena i fotogeneriranih azometin-ilida iz odabranih ftalimida. Kompleksiranjem adamantilftalimidnog derivata s β-CD povećava se iskorištenje adukata.In this PhD thesis synthesis of new phthalimide derivatives and study of their photochemical reactivity are described. Newly synthesized molecules are phthalimide derivatives of adamantane amino acids, where an influence of the distance between the phthalimide (electron acceptor) and the carboxylate (electron donor) on photoinduced electron transfer (PET) and decarboxylation efficiency was investigated. The distance between these groups in the investigated compounds has a significant influence on the decarboxylation efficiency, while PET is the rate-determining step of the whole process. Moreover, study of the influence of different substituents attached to the position 4 of the phthalimide chromophore on the photophysical properties and photochemical reactivity was conducted. The phthalimides bearing electron-donating substituents are generally characterized by reactivity from both singlet and triplet excited states. The fluorescence from these compounds is in competition with PET, and triplet excited state population in the absence of a sensitizer is inefficient. On the contrary, phthalimides bearing electron-withdrawing substituents react mostly from the triplet excited state. However, the nitro derivative is different since it exhibits typical reactivity of the nitrobenzene chromophore. The effect of supramolecular control with cyclodextrins (CD) on [3 + 2] cycloaddition of alkenes and photogenerated azomethine ylides from selected phthalimides was described. Complexation of adamantylphthalimide derivative with β-CD increased the yield of adducts

Fotokemijska dekarboksilacija ftalimidnih derivata

U okviru ove doktorske disertacije provedena je sinteza novih derivata ftalimida i istraživanje fotokemijske reaktivnosti tih spojeva. Novopripravljene molekule su ftalimidni derivati adamantanskih aminokiselina, pri čemu je istražen utjecaj udaljenosti između ftalimidnog kromofora (akceptor elektrona) i karboksilne skupine (donor elektrona) na učinkovitost fotoinduciranog prijenosa elektrona (PET) i dekarboksilacije. Udaljenost tih skupina ima značajan utjecaj na učinkovitost dekarboksilacije istraživanih spojeva, a intramolekulski PET je najsporiji stupanj cijelog procesa. Nadalje, istražen je i utjecaj različitih supstituenata vezanih na položaju 4 ftalimidnog kromofora na fotofizička svojstva i fotokemijsku reaktivnost. Ftalimide s elektron-donorskim supstituentom općenito karakterizira reaktivnost i iz singletnog i iz tripletnog pobuđenog stanja. Fluorescencija tih spojeva je u kompeticiji s PET-om, a populacija tripletnog pobuđenog stanja u odsutnosti senzibilizatora je neučinkovita. S druge strane, ftalimidi s elektron-akceptorskim supstituentom reagiraju uglavnom iz tripletnog pobuđenog stanja. Međutim, nitro-derivat je drukčiji budući da ima reaktivnost karakterističnu za nitrobenzenski kromofor. Istraživan je i utjecaj supramolekulske kontrole s ciklodekstrinima (CD) na [3 + 2] cikloadiciju alkena i fotogeneriranih azometin-ilida iz odabranih ftalimida. Kompleksiranjem adamantilftalimidnog derivata s β-CD povećava se iskorištenje adukata

Photochemical decarboxylation of phthalimide derivatives

U okviru ove doktorske disertacije provedena je sinteza novih derivata ftalimida i istraživanje fotokemijske reaktivnosti tih spojeva. Novopripravljene molekule su ftalimidni derivati adamantanskih aminokiselina, pri čemu je istražen utjecaj udaljenosti između ftalimidnog kromofora (akceptor elektrona) i karboksilne skupine (donor elektrona) na učinkovitost fotoinduciranog prijenosa elektrona (PET) i dekarboksilacije. Udaljenost tih skupina ima značajan utjecaj na učinkovitost dekarboksilacije istraživanih spojeva, a intramolekulski PET je najsporiji stupanj cijelog procesa. Nadalje, istražen je i utjecaj različitih supstituenata vezanih na položaju 4 ftalimidnog kromofora na fotofizička svojstva i fotokemijsku reaktivnost. Ftalimide s elektron-donorskim supstituentom općenito karakterizira reaktivnost i iz singletnog i iz tripletnog pobuđenog stanja. Fluorescencija tih spojeva je u kompeticiji s PET-om, a populacija tripletnog pobuđenog stanja u odsutnosti senzibilizatora je neučinkovita. S druge strane, ftalimidi s elektron-akceptorskim supstituentom reagiraju uglavnom iz tripletnog pobuđenog stanja. Međutim, nitro-derivat je drukčiji budući da ima reaktivnost karakterističnu za nitrobenzenski kromofor. Istraživan je i utjecaj supramolekulske kontrole s ciklodekstrinima (CD) na [3 + 2] cikloadiciju alkena i fotogeneriranih azometin-ilida iz odabranih ftalimida. Kompleksiranjem adamantilftalimidnog derivata s β-CD povećava se iskorištenje adukata.In this PhD thesis synthesis of new phthalimide derivatives and study of their photochemical reactivity are described. Newly synthesized molecules are phthalimide derivatives of adamantane amino acids, where an influence of the distance between the phthalimide (electron acceptor) and the carboxylate (electron donor) on photoinduced electron transfer (PET) and decarboxylation efficiency was investigated. The distance between these groups in the investigated compounds has a significant influence on the decarboxylation efficiency, while PET is the rate-determining step of the whole process. Moreover, study of the influence of different substituents attached to the position 4 of the phthalimide chromophore on the photophysical properties and photochemical reactivity was conducted. The phthalimides bearing electron-donating substituents are generally characterized by reactivity from both singlet and triplet excited states. The fluorescence from these compounds is in competition with PET, and triplet excited state population in the absence of a sensitizer is inefficient. On the contrary, phthalimides bearing electron-withdrawing substituents react mostly from the triplet excited state. However, the nitro derivative is different since it exhibits typical reactivity of the nitrobenzene chromophore. The effect of supramolecular control with cyclodextrins (CD) on [3 + 2] cycloaddition of alkenes and photogenerated azomethine ylides from selected phthalimides was described. Complexation of adamantylphthalimide derivative with β-CD increased the yield of adducts

Application of 4-amino-N-adamantylphthalimide solvatochromic dye for fluorescence microscopy in selective visualization of lipid droplets and mitochondria

4-Amino-N-adamantylphthalimide (1) is a dye with moderate absorptivity (in CH3CN ε363 = 4200 M-1 cm-1) and high quantum yield of fluorescence (ΦF = 0.15-0.80) that exhibits fluorosolvatochromic properties. The dye can be excited at 405 nm and the position of fluorescence maximum and the Stokes shift are well correlated with the ET(30) parameter. The excitation in the near-visible part of the spectrum and low cytotoxicity allow use of the dye in live cell microscopy. Due to its amphiphilic character, the dye stains artificial membranes in liposomes. Using confocal microscopy on two human cancer cell lines, we have shown that 1 stains primarily intracellular lipid droplets. Colocalization experiments with different organelle markers indicated that 1 additionally stains mitochondrial membranes. The fluorosolvatochromism of 1 allows the simultaneous visualization of mitochondria and intracellular lipid droplets in two separate emission channels, which has a potential use in cells and tissues exhibiting intense oxidative metabolism of lipids

The effect of the rate of photoinduced electron transfer on the photodecarboxylation efficiency in phthalimide photochemistry

Reactivity in photoinduced electron transfer reactions (PET) has been investigated in a series of molecules possessing different distances between the electron donor (carboxylate or alkoxyphenyl) and the phthalimide as the electron acceptor. The molecules were strategically designed to separate the donor and the acceptor by a rigid adamantane spacer or through a peptide backbone with different number of amino acid residues. PET was investigated by laser flash photolysis (LFP). Although previous reports demonstrated that the quantum yields of the photodecarboxylation reaction (ΦR) depend on the distance between the donor and acceptor moieties, the measured lifetimes of the triplet excited state did not provide information on the rates of PET. Due to reversible PET and back electron transfer processes in compounds 1-5, the measured lifetimes correspond to the sum of the rate constants for the disappearance of the charge transfer species. In the series of peptides, three different PET processes take place and LFP provided rate constant for the reactions occurring subsequent to the intrastrand PET between the carboxylate and the alkoxyphenyl radical cation. The understanding of the factors that affect intramolecular PET processes is important for the rational design of different applications

Photophysical properties and electron transfer photochemical reactivity of substituted phthalimides

Photochemical reactivity, photophysical and electrochemical properties for a series of N-adamantylphthalimides bearing carboxylic functional groups were investigated. Upon irradiations (with or without a triplet sensitizer), compounds undergo decarboxylation via a photoinduced electron transfer (PET) from the carboxylate to the phthalimide. UV-Vis and fluorescence pH titrations were used to determine pKa values for the prototropic forms, which were put in connection with quantum yields of the reaction (ΦR). Compounds bearing electron donors OH and OCH3 at the phthalimide 4 position are fluorescent (ΦF = 0.02-0.49) and PET takes place from both singlet and triplet excited states. Estimated rate constants for PET in the singlet excited states for methoxy- and amino-substituted phthalimides are (2.0 ± 0.1) × 10^9 s-1and (3.4 ± 1.0) × 10^7 s-1, respectively. Laser flash photolysis (LFP) was conducted to characterize triplet excited states, which are populated less efficiently for compounds with electron donors. The PET is reversible and the overall ΦR depends on the rates for back electron transfer, protonation of the phthalimide radical anion and decarboxylation. Plausible photochemical and photophysical pathways depend on the phthalimide substituents, which is important for the use of phthalimide derivatives in organic synthesis and photocatalysis

Novel Coumarin Derivatives Containing 1,2,4-Triazole, 4,5-Dicyanoimidazole and Purine Moieties: Synthesis and Evaluation of Their Cytostatic Activity

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3–6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8–13) coumarin derivatives and their acyclic nucleoside analogues 14–18. Structures of novel compounds 3–18 were deduced from their 1H- and 13C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC50 = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC50 = 33 µM), HepG2 (IC50 = 25 µM) and SW620 (IC50 = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts