Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Molecules ; 25(14)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664239

RESUMO

Tetraaza-macrocyclic pyridinophane L-Ts, decorated with a p-toluenesulfonyl (tosyl; Ts) group, appear to be a useful tool to provide evidence on how the interplay of various supramolecular forces can help stabilise exotic anionic species such as tribromide (Br3-) anions. Indeed, crystals of (H2L-Ts)(Br3)1.5(NO3)0.5 unexpectedly grew from an acidic (HNO3) aqueous solution of L-Ts in the presence of Br- anions. The crystal structure of this compound was determined by single crystal XRD analysis. Hydrogen bonds, salt-bridges, anion-, - stacking, and van der Waals interactions contribute to stabilising the crystal lattice. The observation of two independent Br3- anions stuck over the π-electron densities of pyridine and tosyl ligand groups, one of them being sandwiched between two pyridine rings, corroborates the significance of anion-π interactions for N-containing heterocycles. We show herein the possibility of detecting anion-π contacts from fingerprint plots generated by Hirshfeld surface analysis, demonstrating the effective usage of this structural investigation technique to further dissect individual contributions of stabilising supramolecular forces.

2.
Chem Commun (Camb) ; 56(54): 7511-7514, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32510075

RESUMO

Quantum chemical and multiscale calculations reveal the mechanistic pathway of two superoxide dismutase mimetic N-alkylated tetra-azacyclophane copper complexes with remarkable activity. The arrangement of the binding site afforded by the bulky alkyl substituents and the coordinated water molecule as a proton source play key roles in the reaction mechanism.

3.
Dalton Trans ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32543616

RESUMO

Three new [1 + 1] macrocycles formed by the reaction of 1H-3,5-bis(chloromethyl)pyrazole with the tosylated amines 1,4,7,10-tetraazadecane (L1), 1,4,8,11-tetraazaundecane (L2) and 1,5,10,14-tetraazatetradecane (L3) are described. Potentiometric studies and HR-ESI-Mass spectrometry show the formation of dimeric binuclear Cu2+ complexes whose organization depends on the type of hydrocarbon chains connecting the amine groups. Furthermore, trinuclear or/and tetranuclear complexes are formed depending also on the length of the polyaminic bridge and on the sequence of the hydrocarbon chains. The crystal structures of the [2 + 2] [Cu2(H(H-1L2))2](ClO4)4·4H2O (1) and [Cu2(H-1L2)2](ClO4)2 (2) complexes show in both of them two macrocycles self-assembled by the metal ions which interconnect their pyrazolate fragments that behave as bis(monodentate) ligands. While in 1 one central amine of each macrocycle binds to the axial position of a distorted square-pyramid and the other ones remain protonated, in 2 all the amine groups are involved in the coordination giving rise to a strongly distorted octahedral geometry. Paramagnetic 1H NMR measurements support that these structures also form in solution. Interestingly, tetranuclear complexes [Cu4(H-1L4)2(OH)2.08](ClO4)2.92Br0.54Cl0.46 (3) and [Pd2.39Cu1.61(H-1L4)2(OH)2](ClO4)2Cl1.33Br0.67·2.87H2O (4) have been isolated for the macrocycle containing the 1,5,9,13-tetraamine chain (L4). 3 has two binucleating units, one of them formed by the pyrazolate moieties and their neighbouring secondary amines and the other by the two central amines of both macrocycles. This latter Cu2+ coordination site is completed by two hydroxide anions as bridging ligands. 4 was obtained from a solution prepared to achieve full formation of the dimeric cage [Cu2(H-1(HL4))2]4+ by addition of K2PdCl4. The Pd2+ ion due to its softer acidic characteristics displaces the Cu2+ ions from the pyrazolate site. UV-vis spectroscopy suggests that the exchange is completed at room temperature after one hour.

4.
Soft Matter ; 16(28): 6514-6522, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32597453

RESUMO

Here we present the preparation and characterization of new biocompatible materials for drug encapsulation. These new gels are based on positively charged [1+1] 1H-pyrazole-based azamacrocycles which minimise the electrostatic repulsions between the negatively charged GMP molecules. Rheological measurements confirm the electroneutral hydrogel structure as the most stable for all the GMP-polyamine systems. Nuclear magnetic resonance (NMR) was employed to investigate the kinetics of the hydrogel formation and cryo-scanning electron microscopy (cryo-SEM) was used to obtain information about the hydrogel morphology, which exhibited a non-homogeneous structure with a high degree of cross-linking. It is possible to introduce isoniazid, which is the most employed antibiotic for tuberculosis treatment, into the hydrogels without disrupting the hydrogel structure at appropriate concentrations for oral administration.

5.
Inorg Chem ; 59(10): 7306-7317, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32379437

RESUMO

We report the synthesis and characterization of the macrocyclic ligand 2,2'-((2-(3,9-bis(carboxymethyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)azanediyl)diacetic acid (H4L) and several of its complexes with lanthanide ions. The structure of the free ligand was determined using X-ray diffraction measurements. Two N atoms of the pyclen moiety in the trans position are protonated in the solid state, together with the exocyclic N atom and one of the carboxylate groups of the ligand. The relaxivity of the Gd3+ complex was found to increase from 6.7 mM-1 s-1 at pH 8.6 to 8.5 mM-1 s-1 below pH ≈ 6.0. Luminescence lifetime measurements recorded from H2O and D2O solutions of the Eu3+ complex evidence the presence of a single complex species in solution at low pH (∼5.0) that contains two inner-sphere water molecules. DFT calculations suggest that the coordination environment of the Ln3+ ion is fulfilled by the four N atoms of the pyclen unit, two oxygen atoms of the macrocyclic acetate groups, and an oxygen atom of an exocyclic carboxylate group. The two inner-sphere water molecules complete coordination number nine around the metal ion. At high pH (∼9.3), the lifetime of the excited 5D0 level of Eu3+ displays a biexponential behavior that can be attributed to the presence of two species in solution with hydration numbers of q = 0 and q = 1. The 1H NMR and DOSY spectra recorded from solutions of the Eu3+ and Y3+ complexes reveal a structural change triggered by pH and the formation of small aggregates at high pH values.

6.
J Med Chem ; 63(3): 1199-1215, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31935092

RESUMO

In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines L1a and L5a displayed remarkable activity with IC50 values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, L1a and L5a failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific Zinquin assay and ZnL2+ stability constant values in solution, strongly supports their cytotoxicity. These data along with quantum mechanical studies have enabled to establish a precise structure-activity relationship. Moreover, L1a and L5a showed appropriate drug-likeness by in silico methods. Based on these promising results, L1a and L5a should be considered a new class of zinc-chelating anticancer agents that deserves further development.


Assuntos
Antineoplásicos/farmacologia , Quelantes/farmacologia , Poliaminas/farmacologia , Zinco/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Quelantes/síntese química , Quelantes/farmacocinética , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Modelos Químicos , Estrutura Molecular , Poliaminas/síntese química , Poliaminas/farmacocinética , Teoria Quântica , Relação Estrutura-Atividade , Zinco/química
7.
Inorg Chem ; 59(2): 1496-1512, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31913029

RESUMO

We report a detailed characterization of Eu3+ and Tb3+ complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (H3tpptac). Tpptac3- displays an overall basicity (∑ log KiH) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln3+ (log KLnL = 17.5-18.7). These complexes are also thermodynamically stable at physiological pH (pEu = 18.6, pTb = 18.0). It should be noted that the pGd value of Gd-tpptac (18.4) is only slightly lower than that of commercially available MRI contrast agents such as Gd-dota (pGd = 19.2). Moreover, a very good selectivity for these ions over the endogenous cations (log KCuL = 14.4, log KZnL = 12.9, and log KCaL = 9.3) is observed. The X-ray structure of the terbium complex shows the metal coordinated by the nine N6O3 donor set of the ligand and one inner-sphere water molecule. DFT calculations result in two Eu-tpptac structures with similar bond energies (ΔE = 0.145 eV): one structure in which the water is coordinated to the metal ion and one structure in which the water molecule is farther away from the ion, bound to the ligand with an OH-π bond. By detailed luminescence experiments, we demonstrate that the europium complex in aqueous solution presents a hydration equilibrium between nine-coordinate, dehydrated [Eu-tpptac]0 and ten-coordinate, monohydrated [Eu-tpptac(H2O)]0 species. A similar trend is observed for the terbium complex. Despite the presence of this hydration equilibrium, the H3tpptac ligand sensitizes Eu3+ and Tb3+ luminescence efficiently in buffered water at physiological pH. Particularly, the terbium complex displays a long excited-state lifetime of 2.24 ms and an overall quantum yield of 33% with a brightness of 3600 M-1 cm-1. Such features of Ln3+ complexes of H3tpptac indicate that this platform appears to be particularly appealing for the further development of luminescent lanthanide labels.

8.
Dalton Trans ; 49(6): 1897-1906, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31970351

RESUMO

A ligand comprised of a macrocyclic pyridinophane core having a pendant arm containing a secondary amine group linked through a methylene spacer to a pyridyl-oxadiazole-phenyl (PyPD) fluorescent system has been prepared (L). The crystal structures of [ZnL](ClO4)2 and [CuL](ClO4)2 show that M2+ is coordinated to all the nitrogen atoms of the macrocyclic core, the secondary amine of the pendant arm and the nitrogen atom of the pyridine group of the fluorescent moiety, the latter bond being clearly weaker than the one with the pyridine of the macrocycle. Solution studies showed the formation of a highly stable Cu2+ complex with 1 : 1 stoichiometry, whereas with Zn2+ least stable complexes were formed and, given the right conditions, a [Zn3L2]6+ species was also detected, but it was not possible to isolate this species in the solid state. Following Zn2+ coordination, a strong chelation-induced enhancement of fluorescence was observed, a behaviour that was not observed with any of the other metal cations tested.


Assuntos
Cobre/química , Corantes Fluorescentes/química , Compostos Macrocíclicos/química , Oxidiazóis/química , Piridinas/química , Zinco/química , Compostos Aza/síntese química , Compostos Aza/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Fluorescência , Corantes Fluorescentes/síntese química , Compostos Macrocíclicos/síntese química , Modelos Moleculares , Oxidiazóis/síntese química , Piridinas/síntese química
9.
Chembiochem ; 21(8): 1167-1177, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31701633

RESUMO

Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid-base properties of the new derivatives have been studied by means of potentiometric titrations, UV/Vis and fluorescence emission spectroscopy. The interaction with G4s and duplex DNA has been explored by using FRET melting assays, fluorescence spectroscopy and circular dichroism. Compared with previous TPA derivatives with macrocyclic substituents, the new ligands reported herein retain the G4 affinity, but display two orders of magnitude higher selectivity for G4 versus duplex DNA; this is most likely due to the ability of the linear substituents to embrace the G4 structure.

10.
Molecules ; 24(15)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357384

RESUMO

A new G-(H2L)-Pd heterogeneous catalyst has been prepared via a self-assembly process consisting in the spontaneous adsorption, in water at room temperature, of a macrocyclic H2L ligand on graphene (G) (G + H2L = G-(H2L)), followed by decoration of the macrocycle with Pd2+ ions (G-(H2L) + Pd2+ = G-(H2L)-Pd) under the same mild conditions. This supramolecular approach is a sustainable (green) procedure that preserves the special characteristics of graphene and furnishes an efficient catalyst for the Cu-free Sonogashira cross coupling reaction between iodobenzene and phenylacetylene. Indeed, G-(H2L)-Pd shows an excellent conversion (90%) of reactants into diphenylacetylene under mild conditions (50 °C, water, aerobic atmosphere, 14 h). The catalyst proved to be reusable for at least four cycles, although decreasing yields down to 50% were observed.


Assuntos
Complexos de Coordenação/química , Grafite/química , Paládio/química , Catálise , Fenômenos Químicos , Concentração de Íons de Hidrogênio , Ligantes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Soluções , Análise Espectral
11.
Dalton Trans ; 48(9): 2881-2885, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30734796

RESUMO

Systematic analyses of the composition and size of metal-organic frameworks built with Zn4O and terephthalic/amino-terephthalic acid mixtures, together with a kinetic assay, reveal how these ligands behave differently, which reveals the complexity of crystal growth in these frameworks and the ability to tune it on purpose.

12.
Eur J Med Chem ; 164: 27-46, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30583247

RESUMO

Despite the continuous research effort that has been made in recent years to find ways to treat the potentially life threatening Chagas disease (CD), this remains the third most important infectious disease in Latin America. CD is an important public health problem affecting 6-7 million people. Since the need to search for new drugs for the treatment of DC persists, in this article we present a panel of new polyamines based on the tripodal structure of tris(2-aminomethyl)amine (tren) that can be prepared at low cost with high yields. Moreover, these polyamines present the characteristic of being water-soluble and resistant to the acidic pH values of stomach, which would allow their potential oral administration. In vitro and in vivo assays permitted to identify the compound with the tren moiety functionalized with one fluorene unit (7) as a potential antichagas agent. Compound 7 has broader spectrum of action, improved efficacy in acute and chronic phases of the disease and lower toxicity than the reference drug benznidazole. Finally, the action mechanisms studied at metabolic and mitochondrial levels shows that the trypanocidal activity of compound 7 could be related to its effect at the glycosomal level. Therefore, this work allowed us to select compound 7 as a promising candidate to perform preclinical evaluation studies.


Assuntos
Doença de Chagas/tratamento farmacológico , Poliaminas/uso terapêutico , Tripanossomicidas/farmacologia , Doença Aguda/terapia , Animais , Doença Crônica/tratamento farmacológico , Desenho de Fármacos , Fluorenos/química , Humanos , Microcorpos/efeitos dos fármacos , Nitroimidazóis/farmacologia , Poliaminas/química , Poliaminas/toxicidade , Solubilidade , Trypanosoma cruzi/efeitos dos fármacos
13.
Inorg Chem ; 57(23): 14484-14488, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30354096

RESUMO

We report here the remarkable catalytic efficiency observed for two Pd(II) azamacrocyclic complexes supported on multiwalled carbon nanotubes (MWCNTs) toward oxygen reduction reactions. Beyond a main (>90%) 4e- process and an onset potential close to or better than those of commercial Pt electrodes, the MWCNTs functionalization strategy, aimed at chemically defined Pd(II)-based catalytic centers, allowed the half-cell to exceed the proton-exchange-membrane fuel-cell reference/target mass activity efficiency set by the U.S. Department of Energy for 2020 (440 mA/mgPGM at 0.9 V vs reversible hydrogen electrode).

14.
Inorg Chem ; 57(17): 10961-10973, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30129755

RESUMO

A new tetraaza-pyridinophane macrocycle (L1) N-alkylated with two isopropyl and one methyl groups symmetrically disposed has been prepared and its behavior compared with those of the unsubstituted pyridinophane (L3) and the related compound with three methyl groups (L2). The protonation studies show that, first, a proton binds to the central methylated amine group of L1, while, second protonation leads to a reorganization of the protons that are at this stage attached to the lateral isopropylated amines. The X-ray structure of [HL1]+ agrees with the UV-vis and NMR studies as well as with the results of DFT calculations. The stability of the Cu2+ complexes decreases on increasing the bulkiness of the alkyl substituents of the amine groups. The crystal structures of [CuL1Cl](ClO4) and [CuL1(H2O)](ClO4)2·H2O show square pyramidal coordination geometries with the ligands disposed in a bent L-shaped conformation. Kinetic studies indicate that the rates of both complexation and ligand dissociation decrease with the bulkiness of the substituents, so that the stability changes are surely the results of compensating effects, complex formation dominating over complex dissociation. The pH dependence of the rate constants for complex formation cannot be explained by consideration of rapid pre-equilibria involving the different protonated forms of the ligand, and it has been interpreted in terms of a mechanism involving an acid-base equilibrium for a reaction intermediate. NBT SOD studies show that the Cu2+ complex of the bulkiest L1 ligand is the one having the highest activity (IC50 = 0.26(5) µM, kcat = 13.7 × 106 M-1 s-1) which can be associated with the poorer σ-donor ability of the tertiary amino groups, and the rigidity of the system, caused by the bulky isopropyl groups.


Assuntos
Cobre/química , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Superóxido Dismutase/metabolismo , Alquilantes/química , Simulação por Computador , Concentração de Íons de Hidrogênio , Íons , Cinética , Ligantes , Conformação Molecular , Difração de Raios X
15.
Chemistry ; 24(42): 10850-10858, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29768679

RESUMO

A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pendant aza-macrocycle(s) (TPA3PY) has been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and the selectivity they show for G4s over duplex DNA were investigated by Förster resonance energy transfer (FRET) melting assays, fluorimetric titrations and circular dichroism spectroscopy. Interestingly, the interactions of the bi- and especially the tri-branched ligands with G4s lead to a very intense redshifted fluorescence emission band that may be associated with intermolecular aggregation between the molecule and DNA. This light-up effect allows the application of the ligands as fluorescence probes to selectively detect G4s.

16.
Chem Commun (Camb) ; 54(31): 3871-3874, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29594279

RESUMO

The binuclear Cu2+ complex of a pyridinophane polyamine ligand ranking amongst the fastest SOD mimetics so far reported displays a remarkable SOD activity enhancement when grafted to the surface of boehmite (γ-AlO(OH)) nanoparticles (BNPs).

17.
Chemistry ; 24(28): 7137-7148, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29570870

RESUMO

EDTA is widely used as an inhibitor of bacterial growth, affecting the uptake and control of metal ions by microorganisms. We describe the synthesis and characterisation of two symmetrical bis-amide derivatives of EDTA, featuring glycyl or pyridyl substituents: AmGly2 and AmPy2 . Metal ion affinities (logK) have been evaluated for a range of metals (Mg2+ , Ca2+ , Fe3+ , Mn2+ , Zn2+ ), revealing less avid binding compared to EDTA. The solid-state structures of AmGly2 and of its Mg2+ complex have been determined crystallographically. The latter shows an unusual 7-coordinate, capped octahedral Mg2+ centre. The antibacterial activities of the two ligands and of EDTA have been evaluated against a range of health-relevant bacterial species, three Gram negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) and a Gram positive (Staphylococcus aureus). The AmPy2 ligand is the only one that displays a significant inhibitory effect against K. pneumoniae, but is less effective against the other organisms. AmGly2 exhibits a more powerful inhibitory effect against E. coli at lower concentrations than EDTA (<3 mm) or AmPy2 , but loses its efficacy at higher concentrations. The growth inhibition of EDTA and AmGly2 on mutant E. coli strains with defects in outer-membrane lipopolysaccharide (LPS) structures has been assessed to provide insight into the unexpected behaviour. Taken together, the results contradict the assumption of a simple link between metal ion affinity and antimicrobial efficacy.


Assuntos
Amidas/química , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Íons/química , Metais/química , Staphylococcus aureus/efeitos dos fármacos , Ligantes
18.
J Am Chem Soc ; 140(11): 3916-3928, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29463085

RESUMO

The reaction of [(PyNMe3)FeII(CF3SO3)2], 1, with excess peracetic acid at -40 °C generates a highly reactive intermediate, 2b(PAA), that has the fastest rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values at 2.07, 2.01, and 1.94. This species was shown to be in a fast equilibrium with a second S = 1/2 species, 2a(PAA), assigned to a low-spin acylperoxoiron(III) center. Unfortunately, contaminants accompanying the 2(PAA) samples prevented determination of the iron oxidation state by Mössbauer spectroscopy. Use of MeO-PyNMe3 (an electron-enriched version of PyNMe3) and cyclohexyl peroxycarboxylic acid as oxidant affords intermediate 3b(CPCA) with a Mössbauer isomer shift δ = -0.08 mm/s that indicates an iron(V) oxidation state. Analysis of the Mössbauer and EPR spectra, combined with DFT studies, demonstrates that the electronic ground state of 3b(CPCA) is best described as a quantum mechanical mixture of [(MeO-PyNMe3)FeV(O)(OC(O)R)]2+ (∼75%) with some FeIV(O)(•OC(O)R) and FeIII(OOC(O)R) character. DFT studies of 3b(CPCA) reveal that the unbound oxygen of the carboxylate ligand, O2, is only 2.04 Å away from the oxo group, O1, corresponding to a Wiberg bond order for the O1-O2 bond of 0.35. This unusual geometry facilitates reversible O1-O2 bond formation and cleavage and accounts for the high reactivity of the intermediate when compared to the rates of hydrogen atom transfer and oxygen atom transfer reactions of FeIII(OC(O)R) ferric acyl peroxides and FeIV(O) complexes. The interaction of O2 with O1 leads to a significant downshift of the Fe-O1 Raman frequency (815 cm-1) relative to the 903 cm-1 value predicted for the hypothetical [(MeO-PyNMe3)FeV(O)(NCMe)]3+ complex.


Assuntos
Compostos de Ferro/química , Oxigênio/química , Teoria Quântica , Espectroscopia de Ressonância de Spin Eletrônica , Conformação Molecular , Espectroscopia de Mossbauer
20.
Int J Biol Macromol ; 109: 143-151, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29247733

RESUMO

Two bis-polyaza pyridinophane derivatives and their monomeric reference compounds revealed strong interactions with ds-DNA and RNA. The bis-derivatives show a specific condensation of GC- and IC-DNA, which is almost two orders of magnitude more efficient than the well-known condensation agent spermine. The type of condensed DNA was identified as ψ-DNA, characterized by the exceptionally strong CD signals. At variance to the almost silent AT(U) polynucleotides, these strong CD signals allow the determination of GC-condensates at nanomolar nucleobase concentrations. Detailed thermodynamic characterisation by ITC reveals significant differences between the DNA binding of the bis-derivative compounds (enthalpy driven) and that of spermine and of their monomeric counterparts (entropy driven). Atomic force microscopy confirmed GC-DNA compaction by the bis-derivatives and the formation of toroid- and rod-like structures responsible for the ψ-type pattern in the CD spectra.


Assuntos
DNA/química , Conformação de Ácido Nucleico , Piridonas/química , Calorimetria , Dicroísmo Circular , Microscopia de Força Atômica , Conformação de Ácido Nucleico/efeitos dos fármacos , Desnaturação de Ácido Nucleico , Piridonas/farmacologia , RNA de Cadeia Dupla/química , Temperatura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA