Design, Synthesis, Spectroscopic Characterisation and In Vitro Cytostatic Evaluation of Novel Bis(coumarin-1,2,3-triazolyl)benzenes and Hybrid Coumarin-1,2,3-triazolyl-aryl Derivatives

In this work, a series of novel 1, 2, 3-triazolyl-coumarin hybrid systems were designed as potential antitumour agents. The structural modification of the coumarin ring was carried out by Cu(I)-catalysed Huisgen 1, 3-dipolar cycloaddition of 7-azido-4-methylcoumarin and terminal aromatic alkynes to obtain 1, 4-disubstituted 1, 2, 3-triazolyl-coumarin conjugates 2a–g, bis(1, 2, 3-triazolyl-coumarin)benzenes 2h–i and coumarin-1, 2, 3-triazolyl-benzazole hybrids 4a–b. The newly synthesised hybrid molecules were investigated for in vitro antitumour activity against five human cancer cell lines, colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma H 460, human T-lymphocyte cells CEM, cervix carcinoma cells HeLa, as well as human dermal microvascular endothelial cells (HMEC-1). Most of these compounds showed moderate to pronounced cytotoxic activity, especially towards MCF-7 cell lines with IC50 = 0.3–32 μM. In addition, compounds 2a–i and 4a–b were studied by UV-Vis absorption and fluorescence spectroscopy and their basic photophysical parameters were determined

Chemical optical sensors based on benzimidazole derivatives

Temelj svakog kemijskog senzorskog sustava je receptor, odnosno kemosenzorska molekula sposobna prepoznati potencijalni analit. Optički kemijski senzori za ione kao receptore često primjenjuju konjugirane D-π-A heterocikličke molekulske sustave, koje osim funkcije prepoznavanja analita, osiguravaju i dobra optička svojstva poput snažne apsorpcije pri visokim valnim duljinama i izražene fluorescencije. Na taj način omogućuju jednostavnu i brzu metodu detekcije iona, često uočljivu i golim okom. Jedna od osnovnih gradivnih jedinica mnogih heterocikličkih senzorskih sustava je benzimidazol. Derivati benzimidazola, osim izražene biološke aktivnosti, pronalaze primjenu u tehnologiji lasera, optoelektronici, kao fluorescentne probe i kemosenzori. Benzimidazolna jezgra ugrađena u push-pull molekulski sustav (D-π-A sustav) može biti elektron-donorska jedinica ili dio konjugiranog mosta te znatno utjecati na fotofizička i senzorska svojstva molekule. U ovom radu su istraženi novi heterociklički sustavi za primjenu u senzorima temeljeni na tri klase kromofora: akrilonitrilna benzimidazolna bojila, benzimidazo[1,2-a] kinolinski derivati i Schiffove baze funkcionalizirane benzimidazolnom jezgrom. Karakterizacijom njihovih fotofizičkih, kiselo-baznih i kompleksirajućih svojstava definirani su odnosi strukture i spektralnih svojstava te procijenjena njihova primjenjivost u senzorskim sustavima za pH i metale. Najbolji kandidati imobilizirani u polimerne senzorske matrice, optode, su pokazali vrlo izraženu fluorescenciju (u plavom, žutom i zelenom spektralnom području) i sposobnost reverziblnog praćenja pH vrijednosti u otopinama u fiziološki relevantnom području (pH 5-8). Istraživanjem su otkrivena jedinstvena fotofizička svojstva nekih od ispitivanih derivata benzimidazola, poput emisije uzrokovane nanoagregacijom molekula u vodenim otopinama. Promjenom pH vrijednosti otopine moguće je reverzibilno utjecati na proces stvaranja nanoagregata u otopini i na taj način uključivati i isključivati pojavu emisije pri 600 nm. Otkrivena svojstva mogu pronaći primjenu u senzorima, bio-oslikavanju i funkcionalnim materijalima. Definirane su smjernice za nastavak istraživanja kemosenzorskih mehanizama i materijala, posebno za praćenje interakcija s metalnim ionima i DNA molekulama. Na temelju dobivenih rezultata je zaključeno da benzimidazolna jezgra predstavlja multifunkcionalnu gradivnu jedinicu u optičkim kemijskim senzorima, s dokazanim potencijalom za razvoj novih funkcionalnih (nano)materijala.Chemosensing molecules capable of assaying cations or anions in solution (“receptors”) are at the core of every optical chemical sensor. Conjugated D-π-A heterocyclic molecular systems play a dual role in optical chemical ion sensors: as receptors they recognise potential analytes and transform it into analytical signal due to their excellent optical properties, such as strong absorption and fluorescence at long wavelengths. This provides a fast and simple ion detection method, often visible by naked eye. A variety of heterocyclic molecules have been employed in the development of optical sensors in which the benzimidazole unit forms one of the key building blocks. In addition to their recognised biological activity, benzimidazole derivatives also find application in optical lasers and optoelectronics, as fluorescent probes and chemosensors. In recent years, emphasis has been placed on chemosensors that possess push-pull structures (D-π-A systems), where the benzimidazole unit may function as an electron-donating moiety or as a part of a conjugating system. This thesis presents the investigation of three classes of novel benzimidazole functionalised heterocyclic chromophore systems as potential chemosensors: acrylonitriles, benzimidazo[1,2-a]quinolines and Schiff bases. The photophysical, acid-base and metal-ion complexing properties of all derivatives have been identified and their structure-property relationships discussed. Their potential for pH and metal-ion sensing has been evaluated, and the best candidates immobilised in polymer matrices (optodes). The optodes showed very strong fluorescence (in the blue, yellow and green spectral regions) and were able to reversibly monitor pH in solution in the physiologically relevant range (pH 5-8). The research has revealed the ability of some derivatives to form emissive nanoaggregates in aqueous solutions. Aggregation-induced emission (AIE) at 600 nm was found to be pH switchable and reversible, demonstrating great potential for applications in chemosensing, bioimaging and functional materials. Further research in the field of benzimidazole based chromophores and materials, and their potential sensing mechanisms and interactions with metal ions and DNA molecules is proposed. The results of the thesis lead to the conclusion that the benzimidazole unit represents an important multifunctional building block in optical chemical sensors, with proven potential for development of novel functional (nano)materials

Chemical optical sensors based on benzimidazole derivatives

Temelj svakog kemijskog senzorskog sustava je receptor, odnosno kemosenzorska molekula sposobna prepoznati potencijalni analit. Optički kemijski senzori za ione kao receptore često primjenjuju konjugirane D-π-A heterocikličke molekulske sustave, koje osim funkcije prepoznavanja analita, osiguravaju i dobra optička svojstva poput snažne apsorpcije pri visokim valnim duljinama i izražene fluorescencije. Na taj način omogućuju jednostavnu i brzu metodu detekcije iona, često uočljivu i golim okom. Jedna od osnovnih gradivnih jedinica mnogih heterocikličkih senzorskih sustava je benzimidazol. Derivati benzimidazola, osim izražene biološke aktivnosti, pronalaze primjenu u tehnologiji lasera, optoelektronici, kao fluorescentne probe i kemosenzori. Benzimidazolna jezgra ugrađena u push-pull molekulski sustav (D-π-A sustav) može biti elektron-donorska jedinica ili dio konjugiranog mosta te znatno utjecati na fotofizička i senzorska svojstva molekule. U ovom radu su istraženi novi heterociklički sustavi za primjenu u senzorima temeljeni na tri klase kromofora: akrilonitrilna benzimidazolna bojila, benzimidazo[1,2-a] kinolinski derivati i Schiffove baze funkcionalizirane benzimidazolnom jezgrom. Karakterizacijom njihovih fotofizičkih, kiselo-baznih i kompleksirajućih svojstava definirani su odnosi strukture i spektralnih svojstava te procijenjena njihova primjenjivost u senzorskim sustavima za pH i metale. Najbolji kandidati imobilizirani u polimerne senzorske matrice, optode, su pokazali vrlo izraženu fluorescenciju (u plavom, žutom i zelenom spektralnom području) i sposobnost reverziblnog praćenja pH vrijednosti u otopinama u fiziološki relevantnom području (pH 5-8). Istraživanjem su otkrivena jedinstvena fotofizička svojstva nekih od ispitivanih derivata benzimidazola, poput emisije uzrokovane nanoagregacijom molekula u vodenim otopinama. Promjenom pH vrijednosti otopine moguće je reverzibilno utjecati na proces stvaranja nanoagregata u otopini i na taj način uključivati i isključivati pojavu emisije pri 600 nm. Otkrivena svojstva mogu pronaći primjenu u senzorima, bio-oslikavanju i funkcionalnim materijalima. Definirane su smjernice za nastavak istraživanja kemosenzorskih mehanizama i materijala, posebno za praćenje interakcija s metalnim ionima i DNA molekulama. Na temelju dobivenih rezultata je zaključeno da benzimidazolna jezgra predstavlja multifunkcionalnu gradivnu jedinicu u optičkim kemijskim senzorima, s dokazanim potencijalom za razvoj novih funkcionalnih (nano)materijala.Chemosensing molecules capable of assaying cations or anions in solution (“receptors”) are at the core of every optical chemical sensor. Conjugated D-π-A heterocyclic molecular systems play a dual role in optical chemical ion sensors: as receptors they recognise potential analytes and transform it into analytical signal due to their excellent optical properties, such as strong absorption and fluorescence at long wavelengths. This provides a fast and simple ion detection method, often visible by naked eye. A variety of heterocyclic molecules have been employed in the development of optical sensors in which the benzimidazole unit forms one of the key building blocks. In addition to their recognised biological activity, benzimidazole derivatives also find application in optical lasers and optoelectronics, as fluorescent probes and chemosensors. In recent years, emphasis has been placed on chemosensors that possess push-pull structures (D-π-A systems), where the benzimidazole unit may function as an electron-donating moiety or as a part of a conjugating system. This thesis presents the investigation of three classes of novel benzimidazole functionalised heterocyclic chromophore systems as potential chemosensors: acrylonitriles, benzimidazo[1,2-a]quinolines and Schiff bases. The photophysical, acid-base and metal-ion complexing properties of all derivatives have been identified and their structure-property relationships discussed. Their potential for pH and metal-ion sensing has been evaluated, and the best candidates immobilised in polymer matrices (optodes). The optodes showed very strong fluorescence (in the blue, yellow and green spectral regions) and were able to reversibly monitor pH in solution in the physiologically relevant range (pH 5-8). The research has revealed the ability of some derivatives to form emissive nanoaggregates in aqueous solutions. Aggregation-induced emission (AIE) at 600 nm was found to be pH switchable and reversible, demonstrating great potential for applications in chemosensing, bioimaging and functional materials. Further research in the field of benzimidazole based chromophores and materials, and their potential sensing mechanisms and interactions with metal ions and DNA molecules is proposed. The results of the thesis lead to the conclusion that the benzimidazole unit represents an important multifunctional building block in optical chemical sensors, with proven potential for development of novel functional (nano)materials

Chemical optical sensors based on benzimidazole derivatives

Temelj svakog kemijskog senzorskog sustava je receptor, odnosno kemosenzorska molekula sposobna prepoznati potencijalni analit. Optički kemijski senzori za ione kao receptore često primjenjuju konjugirane D-π-A heterocikličke molekulske sustave, koje osim funkcije prepoznavanja analita, osiguravaju i dobra optička svojstva poput snažne apsorpcije pri visokim valnim duljinama i izražene fluorescencije. Na taj način omogućuju jednostavnu i brzu metodu detekcije iona, često uočljivu i golim okom. Jedna od osnovnih gradivnih jedinica mnogih heterocikličkih senzorskih sustava je benzimidazol. Derivati benzimidazola, osim izražene biološke aktivnosti, pronalaze primjenu u tehnologiji lasera, optoelektronici, kao fluorescentne probe i kemosenzori. Benzimidazolna jezgra ugrađena u push-pull molekulski sustav (D-π-A sustav) može biti elektron-donorska jedinica ili dio konjugiranog mosta te znatno utjecati na fotofizička i senzorska svojstva molekule. U ovom radu su istraženi novi heterociklički sustavi za primjenu u senzorima temeljeni na tri klase kromofora: akrilonitrilna benzimidazolna bojila, benzimidazo[1,2-a] kinolinski derivati i Schiffove baze funkcionalizirane benzimidazolnom jezgrom. Karakterizacijom njihovih fotofizičkih, kiselo-baznih i kompleksirajućih svojstava definirani su odnosi strukture i spektralnih svojstava te procijenjena njihova primjenjivost u senzorskim sustavima za pH i metale. Najbolji kandidati imobilizirani u polimerne senzorske matrice, optode, su pokazali vrlo izraženu fluorescenciju (u plavom, žutom i zelenom spektralnom području) i sposobnost reverziblnog praćenja pH vrijednosti u otopinama u fiziološki relevantnom području (pH 5-8). Istraživanjem su otkrivena jedinstvena fotofizička svojstva nekih od ispitivanih derivata benzimidazola, poput emisije uzrokovane nanoagregacijom molekula u vodenim otopinama. Promjenom pH vrijednosti otopine moguće je reverzibilno utjecati na proces stvaranja nanoagregata u otopini i na taj način uključivati i isključivati pojavu emisije pri 600 nm. Otkrivena svojstva mogu pronaći primjenu u senzorima, bio-oslikavanju i funkcionalnim materijalima. Definirane su smjernice za nastavak istraživanja kemosenzorskih mehanizama i materijala, posebno za praćenje interakcija s metalnim ionima i DNA molekulama. Na temelju dobivenih rezultata je zaključeno da benzimidazolna jezgra predstavlja multifunkcionalnu gradivnu jedinicu u optičkim kemijskim senzorima, s dokazanim potencijalom za razvoj novih funkcionalnih (nano)materijala.Chemosensing molecules capable of assaying cations or anions in solution (“receptors”) are at the core of every optical chemical sensor. Conjugated D-π-A heterocyclic molecular systems play a dual role in optical chemical ion sensors: as receptors they recognise potential analytes and transform it into analytical signal due to their excellent optical properties, such as strong absorption and fluorescence at long wavelengths. This provides a fast and simple ion detection method, often visible by naked eye. A variety of heterocyclic molecules have been employed in the development of optical sensors in which the benzimidazole unit forms one of the key building blocks. In addition to their recognised biological activity, benzimidazole derivatives also find application in optical lasers and optoelectronics, as fluorescent probes and chemosensors. In recent years, emphasis has been placed on chemosensors that possess push-pull structures (D-π-A systems), where the benzimidazole unit may function as an electron-donating moiety or as a part of a conjugating system. This thesis presents the investigation of three classes of novel benzimidazole functionalised heterocyclic chromophore systems as potential chemosensors: acrylonitriles, benzimidazo[1,2-a]quinolines and Schiff bases. The photophysical, acid-base and metal-ion complexing properties of all derivatives have been identified and their structure-property relationships discussed. Their potential for pH and metal-ion sensing has been evaluated, and the best candidates immobilised in polymer matrices (optodes). The optodes showed very strong fluorescence (in the blue, yellow and green spectral regions) and were able to reversibly monitor pH in solution in the physiologically relevant range (pH 5-8). The research has revealed the ability of some derivatives to form emissive nanoaggregates in aqueous solutions. Aggregation-induced emission (AIE) at 600 nm was found to be pH switchable and reversible, demonstrating great potential for applications in chemosensing, bioimaging and functional materials. Further research in the field of benzimidazole based chromophores and materials, and their potential sensing mechanisms and interactions with metal ions and DNA molecules is proposed. The results of the thesis lead to the conclusion that the benzimidazole unit represents an important multifunctional building block in optical chemical sensors, with proven potential for development of novel functional (nano)materials

Colourimetric and fluorimetric metal ion chemosensor based on a benzimidazole functionalised Schiff base

<p>Herein we present the interaction of benzimidazole based Schiff base <b>1</b> with different metal ions studied by absorption and fluorescence spectroscopies and computational modelling. Compound <b>1</b> exhibits changes in spectroscopic properties upon chelation with specific metal ions. Its strong absorption band at 425 nm is significantly red shifted (Δ<i>λ</i> = 30 nm) only upon the complexation with Al³⁺, an effect observable by a naked eye as a colour change from light- to dark-yellow. Of the metal ions investigated, only Al³⁺ caused any increase in the fluorescence intensity of <b>1</b>. All other metal ions, including K(I), Na(I), Ag(I), Li(I), Zn(II), Co(II) and Hg(II), showed a negligible fluorescence response, while Cu(II) and Fe(III) significantly decreased the fluorescence intensity. Therefore, system <b>1</b> is a promising colourimetric sensor for Al³⁺, and a fluorescence sensor for Cu²⁺ and Fe³⁺ ions. Computational analysis revealed that <b>1</b> is unionized in ethanol solution, while it becomes di-deprotonated to <b>1</b>^<b>2–</b> upon the complexation with Al³⁺. This changes the electronic structure of <b>1</b> and leaves no acidic hydrogen atoms to allow the ESIPT process. On the other hand, the presence of monovalent metal cations induces only mono-deprotonation to <b>1</b>^<b>–</b>, which turns out to be an insufficient electronic change to be spotted in the recorded spectra.</p