Cytosine Complexes Research Articles

Excited States in Single-Stranded and i-Motif DNA with Silver Ions.

We have studied the excited states and structural properties for the complexes of cytosine (dC)10 chains with silver ions (Ag+) in a wide range of the Ag+ to DNA ratio (r) and pH conditions using circular dichroism, steady-state absorption, and fluorescence spectroscopy along with the ultrafast fluorescence upconversion technique. We also calculated vertical electronic transition energies and determined the nature of the corresponding excited states in some models of the cytosine-Ag+ complexes. We show that (dC)10 chains in the presence of silver ions form a duplex stabilized by C-Ag+-C bonds. It is also shown that the i-motif structure formed by (dC)10 chains is destabilized in the presence of Ag+ ions. The excited-state properties in the studied complexes depend on the amount of binding ions and the binding sites, which is supported by the calculations. In particular, new low-lying excited states appear when the second Ag+ ion interacts with the O atom of cytosine in the C-Ag+-C pairs. A similar picture is observed in the case when one Ag+ ion interacts with one cytosine via the N7 atom.

Label-free electrochemical biosensor for ultra-low level detection of Ag(I) using ssDNA functionalized multi-walled carbon nanotube

Prolonged exposure to silver(I) could harm both human health and the environment. This paper proposes the fabrication of a sensitive, selective, and facile electrochemical biosensor based on non-covalent ssDNA-MWNT hybridization to detect the Ag+ ions in an aqueous medium. Exploration by cyclic voltammetry revealed selective detection of Ag+ metal ions by exploiting Cytosine-Cytosine mismatch chemistry to form specific Cytosine-Ag(I)-Cytosine complexes. The biosensor recorded the lowest 1 pM silver ion concentration in the aqueous medium, and real sample studies further proved its potential for trace amount determination in the aqueous medium for environmental monitoring purposes.

Oligonucleotide-Based Reusable Electrochemical Silver(I) Sensor and Its Optimization via Probe Packing Density.

We report herein a selective, sensitive, and reusable electrochemical sensor for the detection of silver(I) ions. This sensor detects Ag+ through a structure-switching electrode-bound DNA by measuring the changes in the electron-transfer efficiency. A single-stranded DNA, featuring a methylene blue (MB)-tagged DNA hairpin structure, strategically provides selective binding for the silver-mediated coordination of cytosine–Ag+–cytosine complexes. The DNA-modified electrode produces a change in the electrochemical signal due to the redox current of the surface-confined MB tag. The “turn-on” signaling upon silver(I) ion binding could be attributed to a conformational change in the MB-tagged DNA from an open structure to a target-induced folding structure. Differential pulse voltammetry of the DNA-modified electrode showed that the MB reduction signal increased linearly with an increase in Ag+ concentrations in a range of 10–200 nM, with a detection limit of 10 nM. The structure-switching silver(I) ion sensor was amenable to regeneration by simply unfolding the electrode-bound MB-tagged DNA in 100 mM ethylenediaminetetraacetic acid, and it could be regenerated with no loss in signal gain upon subsequent silver(I) ion binding. We also demonstrated that by controlling the probe packing density on the electrode surface, the fabrication parameters can be varied to achieve optimal sensor performance.

New Mixed-Ligand Complexes of Cytosine and Its Silver Nanoparticles: Spectral, Analytical, Theoretical and Biological Activity Studies

Novel mixed-ligands complexes of cytosine (M-cytH-isaH, where isaH denotes isatin) and cytosine capped silver nanoparticles (cytH-AgNPs) are synthesized. The complexes are characterized by different spectroscopic techniques and thermal analyses. Cytosine exhibits different binding modes with the metal ions through the ring nitrogen N(3) and/or C=O forming square planar or octahedral geometries. The ESR spectra of the Cu(II) complexes point to the existence of spin exchange interaction between the metal centers. For all complexes, the thermal decomposition of the inner sphere starts at T ~ 200 °C indicating their high thermal stability. Structure of cytH-AgNPs is investigated by proper microscopic techniques; SEM, TEM, EDX and XRD. The crystal pattern of AgNPs is FCC symmetry with spherical shape and an average nanoparticle size of 5.72–16.31 nm. Biological screening of the synthesized compounds shows that Cu(II) complex, [Cu2(cyt)(isa)2Cl], displays the highest antibacterial activity with inhibition zone diameter of 21 mm/mg sample similar to that of ampicillin. Furthermore, only AgNPs exhibits significant antifungal activity against A. flavus where its smaller size is assumed to play an important role in blocking cell communication mechanisms. Density functional theory, DFT, and molecular docking studies are performed to evaluate the quantum chemical parameters and to shed light on the sites of interaction with the selected protein 1bqb of S. aureus. The scoring energy of [Cu2(cyt)(isa)2Cl] is in good agreement with the superior inhibition activity measured experimentally for this complex.

An ultra-sensitive colorimetric detection of Ag ions based on etching AuNP@MnO2 nanoparticles with glutathione by using dark field optical microscopy

Abstract Although colorimetric methods have been developed for the detection of silver ions (Ag+) based on gold nanoparticles aggregation induced by formation cytosine-Ag+-cytosine complexes or high salt centration with dark field microscopy (DFM). However, this state is usually unstable, resulting in the poor accuracy and repeatability of analytical methods. Herein, we have constructed an assay of Ag+ based on MnO2-coated gold nanoparticle (AuNP@MnO2). MnO2 shell can be reduced into Mn2+ by glutathione (GSH). The maximum absorption peak of AuNP@MnO2 significantly changes from 528 nm to 572 nm. Simultaneously, the color of a single nanoparticle becomes from yellow to green under DFM. However, in the presence of Ag+, the etching process of MnO2 is inhibited because of coordination between GSH toward Ag+. The maximum UV absorption peak of AuNP@MnO2 is basically unchanged. The linear equation for Ag+ detection is obtained in the range from 1.0 pM to 5.0 nM with R2 = 0.983 by using DFM. According to 3σ/k rule (where σ is the standard deviation of five blank samples and k is the slope of regression line), the limit of detection (LOD) is calculated to be 0.39 pM. Furthermore, this approach can be applied to detect Ag+ in real sample, showing the good potential for environmental monitoring and water quality control.

Molecular recognition between guanine and cytosine-functionalized nucleolipid hybrid bilayers supported on gold (111) electrodes

A hybrid bilayer lipid membrane (hBLM), constructed with a 1-hexadecanethiol self-assembled interior leaflet and a 1,2-dipalmitoyl-sn-glycero-3-cytidine nucleolipid exterior leaflet, was deposited at the surface of a gold (111) electrode. This system was used to investigate the molecular recognition reaction between the cytosine moieties of the lipid head group with guanine molecules in the bulk electrolyte solution. Electrochemical measurements and photon polarization modulation infrared reflection absorption spectroscopy (PMIRRAS) were employed to characterize the system and determine the extent of the molecular recognition reaction. The capacitance of the hBLM-covered gold electrode was very low (~1 μF cm−2), therefore the charge density at the gold surface was small. Changing the electrode potential had a minimal effect on the complexation between the cytosine moieties and guanine molecules due to small changes in the static electric field across the membrane. This behavior favored the formation of the guanine–cytosine complex.

Synthesis of Pd immobilized on functionalized hexagonal mesoporous silica (HMS–CPTMS–Cy–Pd) for coupling Suzuki–Miyaura and Stille reactions

In this paper, Pd–cytosine complex immobilized on functionalized hexagonal mesoporous silica (HMS–CPTMS–Cy–Pd) as a novel mesoporous catalyst with high activity for the Stille and Suzuki coupling reactions was successfully fabricated. All products were obtained in good to excellent yields at low time reaction. The prepared catalyst has been characterized using various techniques such as FT-IR, XRD, BET, SEM, EDX-MAP, TGA and ICP. Recovery test confirm that the synthesized catalyst can be able to reuse for several times.

Cu(II) complexes of cytosine and 1-methylcytosine with bromide: old motifs and new structures

The preparation from aqueous solutions and crystal structures of the compounds trans-[Cu(1-Mecyt)2Br2] (1), trans-[Cu(cyt)2Br2] (2), [Cu(cyt)4]Br2·2H2O (3), and [Cu(cyt)Br3][Hcyt] (4) (where 1-Mecyt = 1-Methylcytosine and cyt = cytosine) is reported. Compounds 1 and 2 are made of trans-CuL2Br2 molecules [L = 1-Mecyt (1) or cyt (2)]. In 1, the coordination geometry around the central Cu(II) is distorted square pyramidal, while in 2 no such distortion is observed. Two solid-state polymorphs of 1 have been isolated, 1a and 1b, both of which contain no crystallization solvent and thus only differ in the relative disposition of vicinal [Cu(1-Mecyt)2Br2] units through space. As far as we know, 1 is the first example of a 1:2 Cu(II) complex with 1-Mecyt showing a trans arrangement of the ligands. The obtaining of 2 is also worth of note, as this species was previously reported as elusive. Compound 3 comprises tetra-cytosine-Cu(II) cations and bromides, these latter building, together with water molecules, a H-bonded tetrameric [Ow2Br2] motif. Compound 4 is constituted by [Cu(cyt)Br3]− anions and Hcyt+ cations, the cytosinium cations being in the outer metal coordination sphere. Likely, a pH-mediated equilibrium between 2 and 4 exists, 4 being only observable in traces as the neutral 1:2 complex with two metal–cyt direct bonds (2) is the thermodynamically favored product.

Synthesis, Antibacterial Activity, Interaction with Nucleobase and Molecular Docking Studies of 4-Formylbenzoic Acid Based Thiazoles.

Synthesis, characterization and investigation of antibacterial activity of ten novel Schiff base derivatives of 4-formylbenzoic acid is presented. Their structures were determined using 1H and 13CNMR, EI(+)-MS and elemental analyses. Additionally, DFT calculations of interaction energies in complexes of the novel drugs and DNA bases are carried out. Design and synthesis of thiazole derivatives with benzoic acid scaffold to obtain compounds with an improved antibacterial activity. The examined compounds were screened in vitro for antibacterial activity using the broth microdilution method. Geometrical parameters of the investigated complexes were optimized within the Density Functional Theory (DFT) approximation using the B3LYP functional and the 6-311G** basis set. The docking simulations were performed using the FlexX docking module. Among the derivatives, compound 4b showed very strong bacterial activity against staphylococci, MIC 1.95-3.91 µg/ml, micrococci, MIC 0.98 µg/ml, and Bacillus spp., MIC 7.81-15.62 µg/ml. The compounds 4c, 4d, 4e and 4j also showed high bioactivity against staphylococci, MIC 3.91-31.25 µg/ml, and micrococci, MIC 0.98-15.62 µg/ml. Interaction energy values for investigated guanine complexes are about 2 kcal/mol lower than for the corresponding cytosine complexes. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target. To conclude, an efficient and economic method for the synthesis of thiazoles containing benzoic acid moiety has been developed. The results of antibacterial screenings reveal that some obtained compounds show high to very strong antibacterial activity. The DFT calculations showed that interaction of the obtained drugs with guanine is stronger than with cytosine. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target.

Electrochemical DNA probe for Hg2+ detection based on a triple-helix DNA and Multistage Signal Amplification Strategy

In this work, an ultrasensitive electrochemical sensor was developed for detection of Hg2+. Gold nanoparticles decorated bovine serum albumin reduction of graphene oxide (AuNP-BSA-rGO) were used as subsurface material for the immobilization of triple-helix DNA. The triple-helix DNA containing a thiol labelled single-stranded DNA (sDNA) and a thymine-rich DNA (T-rich DNA), which could be unwinded in the present of Hg2+ to form more stable thymine–Hg2+–thymine (T–Hg2+–T) complex. T–Hg2+–T complex was then removed and the sDNA was left on the electrode. At this time, gold nanoparticle carrying thiol labelled cytosine-rich complementary DNA (cDNA-AuNP) could bind with the free sDNA. Meanwhile, the other free cDNA on AuNP could bind with each other in the present of Ag+ to form the stable cytosine–Ag+–cytosine (C–Ag+–C) complex and circle amplification. Plenty of C–Ag+–C could form silver nanoclusters by electrochemical reduction and the striping signal of Ag could be measured for purpose of the final electrochemical detection of Hg2+. This sensor could detect Hg2+ over a wide concentration range from 0.1 to 130nM with a detection limit of 0.03nM.

Analysis of the structural and thermodynamic parameters of the hydrogen bond in complementary pairs of DNA and RNA bases

Density functional methods involving the B3LYP functional and M062X, WB97XD, and B97D ones optimized for calculations of long-range interactions are used to carry out theoretical analysis of the structural and thermodynamic parameters of complementary adenine-thymine, adenine-uracil, and guanine-cytosine base pairs with hydrogen bonds. The calculated values of the structural and thermodynamic parameters are corrected according to the basis superposition error. The enthalpy factor is demonstrated to prevail over the entropy one during the formation of the guanine—cytosine complex, indicating that the equilibrium constant is of great importance. It is discussed whether the M062X, WB97XD, and B97D functionals can be applied to describe hydrogen-bonded systems.

Crystal structure of [{Cu(tren)}2(cytosinato)]·(ClO4)3·0.5H2O (tren = tris(2-aminoethyl)amine) and an overview on intra-molecular interligand interactions affecting metal binding sites of cytosine

Treatment of cytosine with tris(2-aminoethyl)amine (tren) and Cu(ClO4)2·6H2O under alkaline conditions gave a ternary tren–Cu2+–cytosine complex, [{Cu(tren)}2(cytosinato)]·(ClO4)3·0.5H2O, whose crystal structure was determined by X-ray diffraction. In the structure of the [{Cu(tren)}2(cytosinato)]3+ cation, two tren-capped square-pyramidal Cu2+ ions bind to a cytosinate anion, one through the deprotonated N(1) of cytosine with the formation of an intra-molecular interligand hydrogen bond between the keto substituent O(2) of the base and the amino group of tren and the other through both the ring nitrogen N(3) and the exocyclic O(2) of the base, forming a four-membered chelate-ring. An overview on metal bonding properties of N(1)-unsubstituted cytosine observed in so far reported crystal structures is given, emphasizing the significance of intra-molecular interligand interaction as a factor that affects metal-binding sites of cytosine.

From Evaporative to Cooling Crystallisation: An Initial Co-Crystallisation Study of Cytosine and Its Fluorinated Derivative with 4-chloro-3,5-dinitrobenzoic Acid

Two new multi-component molecular complexes of cytosine and 5-fluorocytosine with 4-chloro-3,5-dinitrobenzoic acid are presented. Materials synthesis was achieved initially by evaporative crystallisation and the crystal structures determined. The process was then successfully transferred into a controlled small scale cooling crystallisation environment, with bulk samples shown to be representative of the multi-component product phase, by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) methods. Turbidity measurements are shown to be a valuable process analytical technology probe for characterising the initial stages of molecular complex formation in solution. The significance of these findings for scale-up of crystallisation of multi-component molecular materials and for future transfer into continuous cooling crystallisation is discussed.

Gas Phase Structure of Metal Mediated (Cytosine)2Ag+ Mimics the Hemiprotonated (Cytosine)2H+ Dimer in i-Motif Folding.

The study of metal ion-DNA interaction aiming to understand the stabilization of artificial base pairing and a number of noncanonical motifs is of current interest, due to their potential exploitation in developing new technological devices and expanding the genetic code. A successful strategy has been the synthesis of metal-mediated base pairs, in which a coordinative bond to a central metal cation replaces a H-bond in a natural pair. In this work, we characterized, for the first time, the gas phase structure of the cytosine···Ag+···cytosine (C-Ag+-C) complex by means of InfraRed-MultiPhoton-Dissociation (IR-MPD) spectroscopy and theoretical calculation. The IR-spectrum was confidently assigned to one structure with the Ag+ acting as a bridge between the heteronitrogen atoms in each cytosine (both in the keto-amino form). This structure is biologically relevant since it mimics the structure of the hemiprotonated C-H+-C dimer responsible for the stabilization of the i-motif structure in DNA, with the replacement of the NH···N bond by a stronger N···Ag+···N bond. Moreover, since the structure of the C-Ag+-C complex is planar, it allows an optimum intercalation between pairs of the two antiparallel strand duplex in the DNA i-motif structure.

Watson–Crick and Sugar-Edge Base Pairing of Cytosine in the Gas Phase: UV and Infrared Spectra of Cytosine·2-Pyridone

While keto-amino cytosine is the dominant species in aqueous solution, spectroscopic studies in molecular beams and in noble gas matrices show that other cytosine tautomers prevail in apolar environments. Each of these offers two or three H-bonding sites (Watson-Crick, wobble, sugar-edge). The mass- and isomer-specific S1 ← S0 vibronic spectra of cytosine·2-pyridone (Cyt·2PY) and 1-methylcytosine·2PY are measured using UV laser resonant two-photon ionization (R2PI), UV/UV depletion, and IR depletion spectroscopy. The UV spectra of the Watson-Crick and sugar-edge isomers of Cyt·2PY are separated using UV/UV spectral hole-burning. Five different isomers of Cyt·2PY are observed in a supersonic beam. We show that the Watson-Crick and sugar-edge dimers of keto-amino cytosine with 2PY are the most abundant in the beam, although keto-amino-cytosine is only the third most abundant tautomer in the gas phase. We identify the different isomers by combining three different diagnostic tools: (1) methylation of the cytosine N1-H group prevents formation of both the sugar-edge and wobble isomers and gives the Watson-Crick isomer exclusively. (2) The calculated ground state binding and dissociation energies, relative gas-phase abundances, excitation and the ionization energies are in agreement with the assignment of the dominant Cyt·2PY isomers to the Watson-Crick and sugar-edge complexes of keto-amino cytosine. (3) The comparison of calculated ground state vibrational frequencies to the experimental IR spectra in the carbonyl stretch and NH/OH/CH stretch ranges strengthen this identification.

Reversible Ag+-crosslinked DNA hydrogels

DNA hydrogels, consisting of Y-shaped nucleic acid subunits or of nucleic acid-functionalized acrylamide chains, undergo switchable gel-to-solution transitions. The Ag(+)-stimulated formation of cytosine-Ag(+)-cytosine complexes results in the crosslinking of the units to yield the hydrogels, while the cysteamine-induced elimination of the Ag(+) ions dissociates the hydrogels into a solution phase.

Ternary complex formation between vanadium(III) cytosine and some amino acids

In this work we present the results of the speciation of the ternary vanadium(III)–Cytosine (HCyt) complexes with the amino acids Glycine (HGly), Proline (HPro), α-Alanine (HαAla) and β-Alanine (HβAla), studied by means of electromotive force measurements emf (H) using 3.0mol.dm−3 KCl as the ionic medium at 25°C. The experimental data were analyzed by means of the computational least-squares program LETAGROP, taking into account the hydrolysis of the vanadium(III) cation and the respective stability constants of the binary complexes and the acid base reactions of the amino acids which were kept fixed during the analysis. In the binary vanadium(III)–Cytosine system the formation of the complexes [V(HCyt)]3+, [V(Cyt)]2+, [V(Cyt)(OH)]+, V(Cyt)(OH)2, [V(Cyt)2]+ and V(Cyt)3 was observed. In the ternary systems studied were observed the complexes with the amino acids Glycine, Proline and β-Alanine [V(HCyt)(HL)]3+, [V(Cyt)(HL)]2+, [V(Cyt)(L)]+, V(Cyt)(L)(OH) and [V(Cyt)(L)(OH)2]− were HL represent the neutral form of the amino acid, with α-Alanine were detected the ternary complexes [V(HCyt)(HL)]3+, [V(Cyt)(HL)]2+, [V(Cyt)(L)]+, V(Cyt)(L)(OH). The species distribution diagrams as a function of pH were briefly discussed.

Quantum-chemical study on cytosine nitrosonium complexes

Cytosine complexes with nitrosonium ion were studied by the RI-MP2/L1 method. Addition of nitrosonium ion to cytosine tautomers leads to formation of a set of nitrosonium complexes with different structures (1η–3η). n-Complexes formed via NO+ coordination to the nitrogen and oxygen atoms are energetically more favorable than π-complexes. The complex of cytosine as 4-aminopyrimidin-2(1H)-one tautomer with nitrosonium ion coordinated to the carbonyl oxygen atom occupies the global minimum on the potential energy surface. Structural features of the complexes are discussed.

DNA Base–Gold Nanocluster Complex as a Potential Catalyzing Agent: An Attractive Route for CO Oxidation Process

The important contribution of DNA to modern day nanobiotechnology is sometimes ascribed to its potential role as a programmable building block for the assembly of nanomaterials. In this work, our density functional theory (DFT) based study explores the possibilities of using complexes of DNA bases (viz., adenine (A), thymine (T), guanine (G), and cytosine (C)) as well as DNA base pairs (such as A-T, C-G, and G4-quadruplex) with the gold cluster Au3 as a model catalyst system for oxidation of CO to CO2. The complexes are energetically stable, and our calculated binding energies of the gold cluster–DNA base complexes are found to match closely with the experimentally obtained heat of desorption of DNA bases on Au films. Our results also reveal that the oxidation of CO on these complexes takes place exclusively via an Eley–Rideal (E-R) type of mechanism whereas both E-R and Langmuir–Hinshelwood (L-H) mechanisms for this reaction are observed for a bare Au3 cluster. More interestingly, the CO oxidation reaction on the gold cluster (in the complexes) is found to be more facile, with a lesser activation barrier and higher heat of formation of the products, as compared to that of a pristine Au3 cluster. Our results suggest that DNA base–gold cluster complexes can be an attractive and efficient catalytic model system that can have wider ramifications. Since the nanoscale gold is already known as a potential catalyst for variety of chemical reactions, our approach will richly supplement to the expanding horizons of catalysis involving gold.

Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid

For several years, the non-steroidal anti-inflammatory drug mefenamic acid, MA, has been known to exist as dimorphs (I and II). We report a new metastable polymorph (III) of MA obtained during attempted co-crystallization experiments and establish its stability relationship with existing forms. At elevated temperatures I and III convert to II, as evident from DSC experiments. On the basis of the lattice energy calculations in conjunction with thermal analysis, the stability order is proposed to be I > II > III at ambient conditions, whereas at elevated temperature the order is II > I > III. In either condition III is a metastable form and hence transforms to I at ambient conditions and to II at higher temperatures. Also we report the structural studies of a DMF solvate and a cytosine complex.