Amino acids based on 2,4,5-triarylimidazoles: synthesis and evaluation as new chemosensors for ion recognition

Sciforum Electronic Conference Series, Vol. 17, 2013, b015N-tert-butyloxycarbonyl-4-formylphenylalanine methyl ester and appropriate heterocyclic diones were used in the synthesis of novel fluorescent unnatural amino acids, namely 2,4,5-triarylimidazolyl-alanines. These new compounds were fully characterised by the usual spectroscopic techniques, such as IR and NMR. The photophysical properties of the amino acids were evaluated by UV-Vis absorption and fluorescence spectroscopy in solvents of different character. Interaction studies with biologically and analytically important ions such as F-, OH-, Cu2+ and Fe3+, through spectrophotometric and spectrofluorimetric titrations were carried out to assess their potential as chemosensors.Fundação para a Ciência e a Tecnologia (FCT

New amino acid-based thiosemicarbazones and hydrazones: synthesis and evaluation as fluorimetric chemosensors in aqueous mixtures

A series of new phenylalanine derivatives bearing thiosemicarbazone and hydrazone units at the side chain were synthesised and evaluated as fluorimetric chemosensors for ions. They were tested for the recognition of organic and inorganic anions, (such as AcO-, F-, Cl-, Br-, I-, ClO4-, CN-, NO3-, BzO-, OH-, H2PO4- and HSO4-) and of alkaline, alkaline-earth, and transition metal cations, (such as Na+, K+, Cs+, Ag+, Cu+, Cu2+, Ca2+, Cd2+, Co2+, Pb2+, Pd2+, Ni2+, Hg2+, Zn2+, Fe2+, Fe3+ and Cr3+) in acetonitrile and its aqueous mixtures in varying ratio through spectrofluorimetric titrations. The results indicate that there is a strong interaction through the donor N, O and S atoms at the side chain of the various phenylalanines, with higher sensitivity for Cu2+, Fe3+ and F- in a 1:2 ligand-ion stoichiometry. The photophysical and metal ion sensing properties of these phenylalanines suggest that they can be suitable for incorporation into peptidic chemosensory frameworks.This research was funded by the Foundation for Science and Technology (FCT) for financial support to CQ-UM [PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302)], CQUM (UIDB/00686/2020) and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment with funds from POCI 2010 (FEDER) and FC

Unnatural benz-X-azolyl asparagine derivatives as novel fluorescent amino acids : synthesis and photophysical characterization

A family of new asparagine derivatives bearing benzothiazole and benzimidazole units, functionalised with electron donor or acceptor groups, were synthesized in good to excellent yields. The photophysical characterization of these new heterocyclic amino acids was performed by UV-visible absorption and fluorescence emission studies and revealed that the compounds displayed remarkably high fluorescence quantum yields and Stokes’ shifts, making them good candidates for application as fluorescent probes by incorporation into peptidic frameworks.Fundação para a Ciência e a Tecnologia (FCT

Non-canonical amino acids bearing thiophene and bithiophene: synthesis by an Ugi multicomponent reaction and studies on ion recognition ability

Novel thienyl and bithienyl amino acids with different substituents were obtained by a multicomponent Ugi reaction between a heterocyclic aldehyde, an amine, an acid and an isocyanide. Due to the presence of the sulphur heterocycle at the side chain, these unnatural amino acids are highly emissive and bear extra electron donating atoms so they were tested for their ability to act as fluorescent probes and chemosensors in the recognition of biomedically relevant ions in acetonitrile and acetonitrile/water solutions. The results obtained from spectrophotometric/spectrofluorimetric titrations in the presence of organic and inorganic anions, and alkaline; alkaline-earth and transition metal cations indicated that the bithienyl amino acid bearing a methoxy group is a selective colorimetric chemosensor for Cu2+, while the other (bi)thienyl amino acids act as fluorimetric chemosensors with high sensitivity towards Fe3+ and Cu2+ in a metal-ligand complex with 1:2 stoichiometry. The photophysical and ion sensing properties of these amino acids confirm their potential as fluorescent probes suitable for incorporation into peptidic frameworks with chemosensory ability.Thanks are due to Fundação para a Ciência e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de Química [PEst-C/QUI/UI0686/2013 (F-COMP-01-0124-FEDER-037302)] and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER.info:eu-repo/semantics/publishedVersio

Novel highly emissive non proteinogenic amino acids : synthesis of 1,3,4-thiadiazolyl asparagines and evaluation as fluorimetric chemosensors for biologically relevant transition metal cations

Highly emissive heterocyclic asparagine derivatives bearing a 1,3,4-thiadiazolyl unit at the side chain, functionalised with electron donor or acceptor groups, were synthesised and evaluated as amino acid based fluorimetric chemosensors for metal cations such as Cu2+, Zn2+, Co2+ and Ni2+. The results suggest that there is a strong interaction through the donor heteroatoms at the side chain of the various asparagine derivatives, with high sensitivity towards Cu2+ in a ligand-metal complex with 1:2 stoichiometry. Association constants and detection limits for Cu2+ were calculated. The photophysical and metal ion sensing properties of these asparagine derivatives confirm their potential as fluorimetric chemosensors and suggest that they can be suitable for incorporation into chemosensory peptidic frameworks.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/QUI/66250/2006 (FCOMP-01-0124-FEDER-007428

Síntese e avaliação de análogos heterocíclicos da asparagina como sensores químicos de catiões com importância biológica, ambiental e analítica

Dissertação de mestrado em Técnicas de Caracterização e Análise QuímicaO reconhecimento de uma grande variedade de analitos tais como aniões, catiões, ácidos nucleicos, aminoácidos e açúcares, entre outros, é de extrema importância em diversas áreas de estudo como a Química, Biologia, Medicina ou às Ciências do Ambiente. Os locais de reconhecimento podem ser acoplados a certos grupos capazes de comunicar o processo de coordenação, traduzindo o processo de ligação num sinal facilmente identificável. Os receptores desenvolvidos especialmente para processos de reconhecimento designam-se por sensores químicos. O objectivo deste trabalho experimental consistiu na síntese e caracterização de derivados não naturais de aminoácidos com aplicação como sensores fluorimétricos de catiões metálicos, contendo unidades heterocíclicas fluorescentes e de coordenação na sua cadeia lateral. Foram sintetizados derivados da asparagina, obtidos a partir de reacções do ácido aspártico com vários amino-benzo-X-azoles, em que X = S (benzotiazole) e NH (benzimidazole) com substituintes de diferente carácter electrónico (dador e retirador). Estes compostos foram caracterizados através das técnicas espectroscópicas habituais, tais como a espectroscopia de ressonância magnética nuclear de protão e carbono, infravermelho, ultravioleta-visível e de fluorescência, bem como através de análise elementar e/ou espectrometria de massa. De maneira a avaliar a aplicação dos derivados heterocíclicos de asparagina sintetizados como sensores fluorimétricos de catiões metálicos com interesse ambiental, biológico e analítico, foram realizadas titulações espectrométricas e espectrofotométricas, em acetonitrilo, dos diferentes derivados da asparagina, protegidos nos grupos terminais amino e carboxilo ou apenas protegidos no grupo terminal amino, com os iões Cu2+, Zn2+, Co2+ e Ni2+. Da análise dos resultados obtidos, pode concluir-se que as asparaginas sintetizadas são sensores selectivos para o ião Cu2+, especialmente na forma protegida nos terminais amino e carboxilo.The recognition of a large variety of analytes, such as anions, cations, nucleic acids, amino acids and sugars, among others, is of extreme importance in diverse research areas as Chemistry, Biology, Medicine or Environmental Sciences. The recognition sites can be coupled to certain groups capable of reporting the coordination process, translating it into an easily identifiable signal. The receptors especially designed for recognition processes are chemosensors. The purpose of this experimental work was the synthesis and characterization of unnatural amino acid derivatives with application as fluorimetric chemosensors for metallic cations, bearing fluorescent and coordinating heterocyclic units at their side chain. Asparagine derivatives were synthesized by reaction os aspartic acid with several aminobenz-X-azoles, where X = S (benzothiazole) or NH (benzimidazole), with substituents of different electronic character (donor and acceptor). The resulting compounds were characterized through the usual spectroscopic techniques, such as proton and carbon nuclear magnetic resonance, infrared, ultraviolet-visible absorption and fluorescence, as well elementary analyses and mass spectrometry. In order to evaluate the application of the heterocyclic asparagine derivatives as fluorimetric chemosensors for metallic cations with environmental, biological and analytic relevance, spectrometric and spectrofluorimetric titrations of the different asparagines derivatives, protected at the amino and carboxyl terminal or protected at the amino terminal, with Cu2+, Zn2+, Co2+ and Ni2+ were carried out in acetonitrile. From the obtained results, it can be concluded that the synthesized asparagines are selective chemosensors for Cu2+, especially in their amino and carboxyl terminal protected form.Fundação para a Ciência e Tecnologia (FCT) - Bolsa de investigação inserida no Projecto PTDC/QUI/66250/2006 “Desenvolvimento de novos compostos heterocíclicos como sensores químicos luminescentes e colorimétricos: detecção de aniões e catiões metálicos”

Amino acid based hydrazones: synthesis and evaluation as new chemosensors for ion recognition

Anionic and cationic species are key players in biological, environmental, and chemical processes and there is an interest in the design of artificial receptors for molecular recognition studies. Optical receptors are preferred due the possibility of using low cost and widely available instruments, and consist of a reporting unit, able to change its fluorescence or absorption properties, and a binding unit, for the selective recognition of the anionic/cationic substrate. Colorimetric chemosensors allow a straightforward “naked-eye” detection, whereas fluorescent chemosensors are more sensitive and versatile, offering subnanometer spatial resolution.1 Metallic cations can be complexed through N, O and S donor atoms as in amino acids, at the main and side chains, and in aromatic heterocycles, which are most usually fluorophores. Therefore, the insertion of suitable heterocyclic systems at the side chain of natural amino acids can add extra functionality to the amino acid.2 Anion coordination is based on hydrogen bonding and electrostatic interactions and at amino acids these processes can arise from side and main chain OH and NH groups, whereas in heterocycles the presence of NH groups or suitable substituents such as urea and thiourea groups can provide a site for coordination.3 Therefore, the combination of the above mentioned entities would result in a ditopic system capable of detecting both anions and cations. Bearing in mind our research on the synthesis and application of colorimetric/fluorimetric probes for anions and cations based on heterocycles and amino acids,4 we now report the synthesis of novel hydrazones based on a phenylalanine core (Figure 1). The evaluation of the new amino acid hydrazones as fluorimetric chemosensors was carried out by performing spectrofluorimetric titrations in acetonitrile and in aqueous solutions, in the presence of relevant organic and inorganic anions, and of alkaline, alkaline-earth and transition metal cations. 1H NMR titrations were also conducted in order to gain further insight into the site and mechanism of coordination for anions and cations.Thanks are due to Fundação para a Ciência e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de Química [PEst-C/QUI/UI0686/2011 (F-COMP-01-0124-FEDER-022716)] and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER

Imidazo-benzocrown ether functionalised amino acids: synthesis and fluorimetric chemosensing studies with metal cations

Comunicação em painel - P59Our research group has been engaged on the synthesis and evaluation of fluorimetric chemosensors for anions and cations based on heterocycles and amino acids and their application as fluorescent markers and fluorimetric probes for metal ions [3]. We now report the synthesis of new fluorescent imidazo-benzocrown ether functionalised amino acids and their evaluation as fluorescent chemosensors for biologically relevant metal cations.Fundação para a Ciência e TecnologiaAckowledgements: Thanks are due to Fundação para a Ciência e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de Química [PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302] and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER

Unnatural amino acids based on 2,4,5-triarylimidazoles as fluorescent labels for peptides

Comunicação em painel P32In the present communication, the photophysical characterisation of novel imidazolyl-alanine derivatives bearing heterocyclic moieties is presented, in organic solvents of different character by UV–vis absorption and fluorescence emission. Due to their strongly emissive character, these heterocyclic amino acids could find application as useful building blocks that can add functionality to the resulting peptide.Fundação para a Ciência e a Tecnologia (FCT

Evaluation of an unnatural amino acid as a fluorimetric chemosensor for anion recognition

Molecular recognition is the basis for most biological functions and in recent years the research on compounds capable of recognizing and binding organic and inorganic molecules involved in biological pathways has evolved to mimic as much as possible the natural mechanisms of organization [1]. The development of artificial receptors for recognizingcationic, neutral, and anionic species is growing and has attracted much interest in molecular recognition study and supramolecular chemistry because they play an important role in a wide range of biological, environmental, and chemical processes [2]. The insertion of coded and unnatural amino acids into the backbone of both natural and synthetic polymers can lead to the development of macromolecules possessing biomimetic characteristics, with unique structural and biological properties. By synthetic manipulation at the side chain of the coded amino acids, new functions and functional relationships can be generated as well as altered physicochemical properties, such as luminescence, conducting ability, higher thermal stability and metal ion and other analytes recognition ability, among other properties [3]. Anion coordination by natural amino acids can arise from side chain OH and NH groups (in serine, threonine, tyrosine or arginine and tryptophan, respectively), as well from additional binding withamide NH groups from the backbone, which act as hydrogen-bond donors to the anion [4]. Following our research interests on the synthesis and application of fluorimetric probes for anions and metal cations based on heterocycles and amino acids[5], we now report the evaluation of an unnatural alanine derivative as a fluorimetric chemosensor for the recognition of anions with analytical, biological, and medicinal relevance, through the introduction of oxygen and nitrogen heterocycles as recognition/reporting units in an alanine core. Benzoxazolyl-alanine 1with an imidazole was evaluated for its ability to respond, viachanges in the fluorescence spectra, in the presence of organic and inorganic anions such as halides, through spectrofluorometrictitrations.Fundação para a Ciência e Tecnologia (FCT)Universidade do Minho (UM