RESUMO
Small ring heterocycles, such as epoxides and aziridines, are present in several natural products and are also highly versatile building blocks, frequently involved in the synthesis of numerous bioactive products and pharmaceuticals. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures, multicomponent reactions (MCRs) have been explored in the synthesis and ring opening of these heterocyclic units. In this review, the recent advances in MCRs involving the synthesis and applications of epoxides and aziridines to the preparation of other heterocycles are discussed emphasizing the stereoselectivity of the reactions.
Assuntos
Aziridinas/síntese química , Compostos de Epóxi/síntese química , Aziridinas/química , Produtos Biológicos/química , Compostos de Epóxi/química , Química Verde , Estrutura Molecular , EstereoisomerismoRESUMO
It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested in three breast cell lines: MCF-10, a healthy cell; MCF-7, a hormone responsive cancer cell; and MDA-MB-231, a triple negative breast cancer cell. Both aziridines and their precursors, ß-amino alcohols, showed activity towards these cells, and some of the compounds showed higher selectivity index than cisplatin, the drug used as control. When the type of cell death was investigated, the synthesized compounds demonstrated higher apoptosis and lower necrosis rates than cisplatin, and when the mechanism of action was studied, the compounds were shown to interact with DNA via its minor groove instead of alkylation or intercalation.
Assuntos
Amino Álcoois/farmacologia , Antineoplásicos/farmacologia , Aziridinas/farmacologia , DNA/efeitos dos fármacos , Alquilação/efeitos dos fármacos , Amino Álcoois/química , Antineoplásicos/química , Aziridinas/química , Linhagem Celular , Cisplatino/química , Cisplatino/farmacologia , DNA/metabolismo , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
B3LYP calculations, ChelpG atomic charges, and quantum theory of atoms in molecules (QTAIM) integrations were used to investigate the binary (1:1) and ternary (1:2) hydrogen-bonded complexes formed by aziridine (1) and ammonia (2). In a series of analysis, geometry data, electronic parameters, vibrational oscillators, and topological descriptors were used to evaluate hydrogen bond strength, and additionally to determine the more prominent molecular deformations upon the formation of C(2)H(5)N···NH(3) (1:1) and C(2)H(5)N···2NH(3) (1:2) systems. Taking a spectroscopic viewpoint, results obtained from analysis of the harmonic infrared spectrum were examined. From these, new vibrational modes and red- and blue-shifts related to the stretch frequencies of either donors or acceptors of protons were identified. Furthermore, the molecular topology of the electronic density modeled in accord with QTAIM was absolutely critical in defining bond critical points (BCP) and ring critical points (RCP) on the heterocyclic structures. Taking all the results together allowed us to identify and characterize all the N···H hydrogen bonds, as well as the strain ring of the aziridine and its stability.
Assuntos
Amônia/química , Aziridinas/química , Simulação por Computador , Modelos Moleculares , Ligação de Hidrogênio , Modelos Químicos , Conformação Molecular , Teoria Quântica , Espectrofotometria Infravermelho , TermodinâmicaRESUMO
Separative extended gate field effect transistor (SEGFET) type devices have been used as an ion sensor or biosensor as an alternative to traditional ion sensitive field effect transistors (ISFETs) due to their robustness, ease of fabrication, low cost and possibility of FET isolation from the chemical environment. The layer-by-layer technique allows the combination of different materials with suitable properties for enzyme immobilization on simple platforms such as the extended gate of SEGFET devices enabling the fabrication of biosensors. Here, glucose biosensors based on dendrimers and metallophthalocyanines (MPcs) in the form of layer-by-layer (LbL) films, assembled on indium tin oxide (ITO) as separative extended gate material, has been produced. NH(3)(+) groups in the dendrimer allow electrostatic interactions or covalent bonds with the enzyme (glucose oxidase). Relevant parameters such as optimum pH, buffer concentration and presence of serum bovine albumin (BSA) in the immobilization process were analyzed. The relationship between the output voltage and glucose concentration shows that upon detection of a specific analyte, the sub-products of the enzymatic reaction change the pH locally, affecting the output signal of the FET transducer. In addition, dendritic layers offer a nanoporous environment, which may be permeable to H(+) ions, improving the sensibility as modified electrodes for glucose biosensing.
Assuntos
Técnicas Biossensoriais/instrumentação , Dendrímeros/química , Glucose/análise , Indóis/química , Níquel/química , Transistores Eletrônicos , Aspergillus niger/enzimologia , Aziridinas/química , Soluções Tampão , Glucose Oxidase/metabolismo , Concentração de Íons de Hidrogênio , Isoindóis , ReciclagemRESUMO
A highly regio- and stereoselective synthesis of novel ß,γ-disubstituted γ-lactams with either an anti or syn relative configuration was developed from readily available epoxide and aziridine acetates. The key steps include the regio- and diastereocontrolled nucleophilic ring-opening of these three-membered heterocycles followed by mild reductive cyclization of the γ-azido ester intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)-4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main features of this versatile synthesis of functionalized γ-lactams include the involvement of inexpensive reagents and mild conditions together with high chemical efficiency.
Assuntos
Acetatos/química , Aziridinas/química , Compostos de Epóxi/química , Pirrolidinonas/química , Pirrolidinonas/síntese química , beta-Lactamas/química , beta-Lactamas/síntese química , Indicadores e Reagentes/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
B3LYP/6-311++G(d,p) calculations were used to predict some molecular properties of the C2H6N+...BeH2, C2H6N...MgH2, C3H8N...BeH2 and C3H8N+...MgH2 dihydrogen-bonded complexes. In these systems, it was demonstrated that the C2H6N+ and C3H8N+ protonated rings are potential candidates to bind with protonic hydrogens derived from alkaline earth metal compounds, BeH2 and MgH2. In terms of structural parameters and quantification of the dihydrogen bond energies, we should mention that the C2H6N+ three-membered ring provides the formation of stronger bound systems, which are 4.0 kJ mol-1 more stables than C3H8N+ four-membered ones. As complement, the analysis of the infrared spectrum indicated that red-shifts and blue-shifts are occurring in the N-H bonds of both C2H6N+ and C3H8N+ cationic rings. However, these two vibrational shifts were also verified on BeH2 and MgH2, what lead us to affirm that cationic compounds derived from small nitrogen rings and earth alkaline molecules are able to form unusual dihydrogen-bonded complexes by means of distinct spectroscopic phenomena, the red-shits and blue-shifts.
Assuntos
Azetidinas/química , Aziridinas/química , Cátions/química , Metais Alcalinoterrosos/química , Prótons , Ligação de Hidrogênio , Modelos Químicos , Modelos Teóricos , TermodinâmicaRESUMO
This theoretical study presents a comparative analysis of the molecular properties of heterocyclic (C2H4O...HF and C2H5...HF) and homocyclic (C3H6...HF) hydrogen-bonded complexes. Initially, the equilibrium geometries of these complexes were analyzed in detail at the B3LYP/6-311++G(d,p) level of theory. Subsequently, the interaction energies and polarizabilities were also evaluated, as well as the infrared stretch frequencies and absorption intensities. In addition, by combining intermolecular criteria and charge density concepts, calculations of Bader's theory of atoms in molecules were used to determine the maxima and minima for electron density in order to measure the strength of the n...H and ppi...H hydrogen bonds. Finally, the possibility of an F...H(alpha) secondary interaction between the fluoride (F) of hydrogen fluoride and the axial hydrogen atoms (H(alpha)) of the C2H4O and C2H5N heterocyclic rings was explored.
Assuntos
Aziridinas/química , Ciclopropanos/química , Óxido de Etileno/química , Ácido Fluorídrico/química , Modelos Químicos , Modelos Moleculares , Ligação de Hidrogênio , Computação MatemáticaRESUMO
Photoirradiation of nitrogen-saturated aqueous solutions containing aluminum phthalocyanine tetrasulfonate (AlPcS4) at 675 nm in the presence of 2,5-dichloro-diaziridinyl-1,4-benzoquinone (AZDClQ) and hypoxanthine (HX) produces the oxidized HX derivatives, xanthine (X) and uric acid (UA). Concentrations of the AZDClQ semiquinone, X and UA increase at the expense of HX with an increase in irradiation time. Almost negligible decomposition of HX, as well as very low amounts of X, are detected if photolysis occurs under identical conditions but in the absence of AZDClQ. Addition of calf-thymus DNA produces quinone-DNA covalent adducts after photolysis of anaerobic samples containing quinone, DNA and AlPcS4, in the presence or absence of HX and at pH 5.5. However, larger amounts of quinone-DNA adducts are detected if HX is present. The results presented here could have applications in the photodynamic treatment of hypoxic tissues such as solid tumors, under conditions of high HX concentration, where Type-I pathways could be more important than singlet oxygen generation.
Assuntos
Aziridinas/química , Benzoquinonas/química , Hipoxantina/química , Indóis/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Xantina/química , Alquilação , DNA/química , Estrutura Molecular , OxirreduçãoRESUMO
The formation and 2-amino alcohol catalyzed addition of arylzinc reagents from and with boronic acids, respectively, is drastically accelerated to a few minutes under microwave irradiation without loss of enantioselectivity (up to 98% ee). Of the amino acid derived catalysts tested, the conformationally restricted bulky substituted aziridine-2-methanols derived from serine show the best overall performance in the formation of diarylmethanols.
Assuntos
Álcoois/síntese química , Aldeídos/química , Aziridinas/química , Compostos Organometálicos/química , Zinco/química , Álcoois/química , Álcoois/efeitos da radiação , Aldeídos/efeitos da radiação , Aziridinas/efeitos da radiação , Ácidos Borônicos/química , Ácidos Borônicos/efeitos da radiação , Catálise , Ligantes , Micro-Ondas , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/efeitos da radiação , Estereoisomerismo , Zinco/efeitos da radiaçãoRESUMO
The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the immobility time of mice evaluated in the FST, an antidepressant-like profile of action similar to imipramine, a well-known standard antidepressant drug used for comparison, without compromising the animals' motor performance. The putative antidepressant-like action demonstrated here indicates their viability for the development of new therapeutic options for the treatment of depression.