Nucleotides In Aqueous Solution Research Articles

Investigation of Melphalan interaction as an alkylating agent with nucleotides by using surface enhanced Raman spectroscopy (SERS)

SERS (Surface Enhanced Raman Spectroscopy) is a new Raman spectroscopy which relies on Surface Plasmon Resonance (SPR) of metal nanoparticles. We have applied colloidal silver and gold nanoparticles as amplifier agents to enhance nucleotide Raman signals. It is observed that without these enhancing agents, it is impossible to investigate nucleotide spectrum due to weak Raman signals. Interaction mechanism of Melphalan, an anticancer drug with four nucleotides (Adenine, Cytosine, Guanine, Thymine) was investigated using SERS to detect and identify changes due to alkylating process in Raman spectra. After incubating Melphalan drug with nucleotides for 24 h at 37 °C, some changes occurred in SERS spectrum and interpretation of SERS spectra revealed the influence of the alkyl substitution on peaks and Raman shifts. After incubation of Melphalan with each nucleotide, intensity of relevant SERS signals assigned to Amid III group of Cytosine and Amid I of Thymine decreased significantly, confirming alkylating taking place. In this study, we also investigated the effect of nanoparticles type on nucleotide spectrum. We could not obtain useful information in the cases of guanine nucleotide. The SERS spectrum of Cytosine as an example of nucleotides in aqueous solution compared to solid state and results demonstrated that in solid state better signals were obtained than in liquid state.

Hyper Rayleigh scattering from DNA nucleotides in aqueous solution.

Nucleotides are organic compounds consisting of a phosphate group, a nitrogenous base, namely adenine (A), thymine (T), cytosine (C), or guanine (G), and a sugar, here deoxyribose. The magnitude of the first hyperpolarizability β of these four DNA nucleotides was determined in aqueous solution with the nonlinear optical technique of hyper rayleigh scattering under non resonant conditions at a fundamental wavelength of 800nm. The smallest value is found to be 1.67 ± 0.15 × 10-30 esu for thymidine-5'-monophosphate and the highest is 1.76 ± 0.16 × 10-30 esu for 2'-guanosine-5'-monophosphate. Polarization resolved studies were also performed to question the symmetry of the first hyperpolarizability tensor and access the ratio of some elements of the first hyperpolarizability tensor. These experimental results were then compared to the theoretical values of these first hyperpolarizabilities obtained with the density functional theory at the level of the PCM-B3LYP/6-31G+(d) basis and taking into account the solvent.

Molecular Receptors for Recognition and Sensing of Nucleotides.

Nucleotides are constituents of nucleic acids and they have a variety of functions in cellular metabolism. Synthetic receptors and sensors are required to reveal the role of nucleotides in living organisms and mechanisms of signal transduction events. In recent years, a large number of nucleotide-selective synthetic receptors have been devised, which utilize different molecular designs and sensing mechanisms. This Minireview presents recent progress in the design of synthetic molecular receptors for selective recognition of nucleotides in aqueous solution. The binding properties of receptors and the origins of their selectivity for a particular nucleotide are discussed.

Mathematical Structure for Electromagnetic Frequencies that May Reflect Pilot Waves of Bohm’s Implicate Order

The mathematical basis for the earlier reported spectrum of discrete electromagnetic field (EMF) frequencies that were shown to affect health and disease is substantiated and generalized in the present paper. The particular EMF pattern was revealed by a meta-analysis of, now, more than 500 biomedical publications that reported life-sustaining as well as life-decaying EMF frequencies. These discrete eigenfrequency values can be related to supposed bio-resonance of solitons or polaron quasi particles in life systems. Bio-solitons are conceived as self-reinforcing solitary waves that are constituting local fields, being involved in intracellular geometric ordering and patterning, as well as in intra- and inter-cellular signalling. Literature search, revealed very similar frequency patterns for wave resonances of nucleotides in aqueous solution, for a candidate RNA-catalyst, as well as for sound-induced vibrations evoked in thin vibrating membranes. This collective evidence points at a generalized biophysical algorithm underlying complexity in nature, evidently manifest in both animate and non-animate modalities. The detected EMF eigenfrequencies could be arithmetically scaled according to an adapted Pythagorean tuning. The mathematical analysis shows that the derived arithmetical scale exhibits a sequence of unique products of integer powers of 2, 3 and a factor . This generalized semi-harmonic frequency spectrum may reflect a discrete pilot-wave structure that can be interpreted as a, so called, hidden variable in Bohm’s causal interpretation of quantum field theory.

Reactivity of prehydrated electrons toward nucleobases and nucleotides in aqueous solution.

DNA damage induced via dissociative attachment by low-energy electrons (0 to 20 eV) is well studied in both gas and condensed phases. However, the reactivity of ultrashort-lived prehydrated electrons ([Formula: see text]) with DNA components in a biologically relevant environment has not been fully explored to date. The electron transfer processes of [Formula: see text] to the DNA nucleobases G, A, C, and T and to nucleosides/nucleotides were investigated by using 7-ps electron pulse radiolysis coupled with pump-probe transient absorption spectroscopy in aqueous solutions. In contrast to previous results, obtained by using femtosecond laser pump-probe spectroscopy, we show that G and A cannot scavenge [Formula: see text] at concentrations of ≤50 mM. Observation of a substantial decrease of the initial yield of hydrated electrons ([Formula: see text]) and formation of nucleobase/nucleotide anion radicals at increasing nucleobase/nucleotide concentrations present direct evidence for the earliest step in reductive DNA damage by ionizing radiation. Our results show that [Formula: see text] is more reactive with pyrimidine than purine nucleobases/nucleotides with a reactivity order of T > C > A > G. In addition, analyses of transient signals show that the signal due to formation of the resulting anion radical directly correlates with the loss of the initial [Formula: see text] signal. Therefore, our results do not agree with the previously proposed dissociation of transient negative ions in nucleobase/nucleotide solutions within the timescale of these experiments. Moreover, in a molecularly crowded medium (for example, in the presence of 6 M phosphate), the scavenging efficiency of [Formula: see text] by G is significantly enhanced. This finding implies that reductive DNA damage by ionizing radiation depends on the microenvironment around [Formula: see text].

Understanding the Interaction between Low-Energy Electrons and DNA Nucleotides in Aqueous Solution.

Reactions that can damage DNA have been simulated using a combination of molecular dynamics and density functional theory. In particular, the damage caused by the attachment of a low energy electron to the nucleobase. Simulations of anionic single nucleotides of DNA in an aqueous environment that was modeled explicitly have been performed. This has allowed us to examine the role played by the water molecules that surround the DNA in radiation damage mechanisms. Our simulations show that hydrogen bonding and protonation of the nucleotide by the water can have a significant effect on the barriers to strand breaking reactions. Furthermore, these effects are not the same for all four of the bases.

Streptomycin Hydrazone Derivatives: Synthesis and Molecular Recognition in Aqueous Solution

Five hydrazone derivatives of streptomycin were synthetized (D0h, D1ph, D2bt, D3dctf, D4ag) and characterized by IR, 1H and 13C NMR spectroscopy, mass spectrometry and elemental analysis. Protonation constants were determined by potentiometry for all derivatives. D1ph and D2bt derivatives were investigated as receptors of dicarboxylates and adenine nucleotides in aqueous solution by potentiometric and 1H NMR titrations. D1ph and D2bt derivatives have the highest affinity with AMP and ATP, respectively, which shows that electrostatic forces are not always the dominant factor in binding of streptomycin derivatives with nucleotides, but the conformational fit between them. Calculated structures at the DFT level of the D1ph derivative bonded with either AMP or ADP showed that the complexes are stabilized by the formation of multiple interactions with the receptors. The antibiotic activity of the derivatives was explored and compared with native streptomycin.

Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution.

The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5'-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to π* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5'-monophosphate, and adenosine 5'-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety.

The dielectric response of interfacial water—from the ordered structures to the single hydrated shell

Water is the universal solvent in nature. Does this imply, however, that its interaction with its environment is also a universal feature? While this question maybe too fundamental to be answered by one method only, we present evidence that the broadening of the dielectric spectra of water presents universal features of dipolar interactions with different types of matrixes. If in aqueous solutions the starting point of water’s state can be considered as bulk, with only partial interactions with the solute, then the state of water adsorbed in heterogeneous materials is determined by various hydration centers of the inhomogeneous material (the matrix) and it is significantly different from the bulk. In both cases, the dielectric spectrum of water is symmetrical and can be described by the Cole–Cole (CC) function. The phenomenological model that describes a physical mechanism of the dipole–matrix interaction in complex systems underlying the CC behavior has been applied to water adsorbed in porous glasses. It was then extended to analyses of the dynamic and structural behavior of water in nonionic and ionic aqueous solutions. The same model is then used to analyze the CC relaxation processes observed in clays, aqueous solutions of nucleotides, and amino acids.

Discrimination of nucleotides by single fluorescence sensor under solvent-dependent recognition patterns

Abstract The chemosensor based on Zn complex of 1-[bis(pyridine-2-ylmethyl)amino]methylpyrene ( 1 · Zn ) was synthesized for detection of nucleotides in aqueous solution. This sensor has a high selectivity for PPi in aqueous solution. However, in the solution of DMSO:HEPES (0.01 M, pH 7.4, 90:10, v/v), 1 · Zn selectively bound nucleoside polyphosphates such as ATP and UTP with a large fluorescence enhancement. Tremendously different recognition patterns of 1 · Zn toward various phosphate anion based nucleotides in the two solvent systems encouraged us to discriminate the structurally similar nucleotide anions. The principal component analysis (PCA) was applied to discriminate 10 nucleotides in two solvent systems. This approach permits the identification of 10 phosphate analytes with nearly 100% accuracy from a single sensor in two solvent systems. To illustrate the utility of this approach for ATP hydrolysis application, the ratios between the product of reaction (PPi) and the reactant (ATP) were plotted versus the ratios of fluorescence intensity. The graph can be used for quantitative prediction of the PPi and ATP ratios with the detection limit of 2:8.

ChemInform Abstract: One-Electron-Reduction Potentials of Pyrimidine Bases, Nucleosides, and Nucleotides in Aqueous Solution. Consequences for DNA Redox Chemistry.

The reduction potentials in aqueous solution of the pyrimidine bases, nucleosides, and nucleotides of uracil (U) and thymine (T) were determined using the technique of pulse radiolysis with time-resolved spectrophotometric detection. The electron adducts of U and T were found to undergo reversible electron exchange with a series of ring-substituted N-methylpyridinium cations with known reduction potential. From the concentrations of the pyrimidine electron adducts and the reduced N-methylpyridinium compounds at electron-transfer equilibrium, the thermodynamical equilibrium constants wereobtained and from these the reduction potentials

Vertical Ionization Potentials of Nucleobases in a Fully Solvated DNA Environment

Vertical ionization potentials (IPs) of nucleobases embedded in a fully solvated DNA fragment (12-mer B-DNA fragment + 22 sodium counterions + 5760 water molecules equilibrated to 298 K) have been calculated using a combined quantum mechanical molecular mechanics (QM/MM) approach. Calculations of the vertical IP of the anion Cl(-) are reported that support the accuracy of the application of a QM/MM method to this problem. It is shown that the pi nucleotide HOMO origin for the emitted electron is localized on the base by the hydration structure surrounding the DNA in a way similar to that recently observed for pyrimidine nucleotides in aqueous solutions (Slavicek, P.; et al. J. Am. Chem. Soc. 2009, 131, 6460). In a first step, a high level of theory, CCSD(T)/aug-cc-pVDZ, was used to calculate the vertical IP of each of the four single bases isolated in the QM region while the remaining DNA fragment, counterions, and water solvent molecules were included in the MM region. The calculated vertical IPs show a large positive shift of 3.2-3.3 eV compared to the corresponding gas-phase values. This shift is similar for all four DNA bases. The origin of the large increase in vertical IPs of nucleobases is found to be the long-range electrostatic interactions with the solvation structure outside the DNA helix. Thermal fluctuations in the fluid can result in IP changes of roughly 1 eV on a picosecond time scale. IPs of pi-stacked and H-bonded clusters of DNA bases were also calculated using the same QM/MM model but with a lower level of theory, B3LYP/6-31G(d=0.2). An IP shift of 4.02 eV relative to the gas phase is found for a four-base-pair B-DNA duplex configuration. The primary goal of this work was to estimate the influence of long-range solvation interactions on the ionization properties of DNA bases rather than provide highly precise IP evaluations. The QM/MM model presented in this work provides an attractive method to treat the difficult problem of incorporating a detailed long-range structural model of physiological conditions into investigations of the electronic processes in DNA.

Extent of metal ion–sulfur binding in complexes of thiouracil nucleosides and nucleotides in aqueous solution

Previously published stability constants of several metal ion (M 2+) complexes formed with thiouridines and their 5′-monophosphates, together with recently obtained log K M ( U ) M versus p K U H plots for M 2+ complexes of uridinate derivatives (U −) allowed now a quantitative evaluation of the effect that the exchange of a (C)O by a (C)S group has on the stability of the corresponding complexes. For example, the stability of the Ni 2+, Cu 2+ and Cd 2+ complexes of 2-thiouridinate is increased by about 1.6, 2.3, and 1.3 log units, respectively, by the indicated exchange of groups. Similar results were obtained for other thiouridinates, including 4-thiouridinate. The structure of these complexes and the types of chelates formed (involving (N3) − and (C)S) are discussed. A recently advanced method for the quantification of the chelate effect allows now also an evaluation of several complexes of thiouridinate 5′-monophosphates. In most instances the thiouracilate coordination dominates the systems, allowing only the formation of small amounts of phosphate-bound isomers. Among the complexes studied only the one formed by Cu 2+ with 2-thiouridinate 5′-monophosphate leads to significant amounts of the macrochelated isomer, which means that in this case Cu 2+ is able to force the nucleotide from the anti to the syn conformation, allowing thus metal ion binding to both potential sites and this results in the formation of about 58% of the macrochelated isomer. The remaining 42% are species in which Cu 2+ is overwhelmingly coordinated to the thiouracilate residue; Cu 2+ binding to the phosphate group occurs in this case only in trace amounts.

Pattern-based sensing of nucleotides in aqueous solution with a multicomponent indicator displacement assay

A multicomponent indicator displacement assay (MIDA) based on an organometallic receptor and three dyes can be used for the identification and quantification of nucleotides in aqueous solution at neutral pH.

Extent of metal ion-sulfur binding in complexes of thiouracil nucleosides and nucleotides in aqueous solution

Extent of metal ion-sulfur binding in complexes of thiouracil nucleosides and nucleotides in aqueous solution

Electron Attachment to Nucleotides in Aqueous Solution

Understanding DNA strand breaks: The study of electron attachment to the nucleotides 5′-dTMPH and 5′-dTMP− (see figure) in aqueous solution demonstrates that the electron affinities of nucleotides are nearly independent of the existence of counterions in aqueous solution. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2267/2006/z600294_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Corrigendum: Synthesis of 1,3-{Di-[N-bis(dimethylamino)methane]}-benzyl-diamide and its Molecular Recognition of Nucleotides in Aqueous Solution

Corrigendum: Synthesis of 1,3-{Di-[N-bis(dimethylamino)methane]}-benzyl-diamide and its Molecular Recognition of Nucleotides in Aqueous Solution

Synthesis of 1,3-{Di-[N-bis(dimethylamino)methane]}- benzyl-diamide and its Molecular Recognition of Nucleotides in Aqueous Solution

1,3-Di-{N-[bis(dimethylamino)methane]}benzyl-diamide 1 was synthesized by the reaction of isophthaloyl dichloride with 1,1,3,3-tetramethylguanidine (TMG). Its structure was confirmed by IR, 1H NMR, EI-MS and elemental analysis. 1H NMR results of the interaction of 1 with phosphate-containing biomolecules showed it has the ability of selective molecular recognition for nucleotides.

The substitution mechanism of [Ruiii(edta)(H2O)]− with DNA bases, nucleoside and nucleotides in aqueous solution revisited

The substitution reactions of [RuIII(edta)(H2O)]− (edta = ethylenediaminetetraacetate) with adenine, adenosine and the corresponding 5′-nucleotides (Nu), viz. adenosine-5′-monophosphate (AMP), adenosine-5′-diphosphate (ADP) and adenosine-5′-triphosphate (ATP), have been studied kinetically as a function of nucleotide concentration at various temperatures (5 to 30 °C) at a fixed pH of 4.6 to contribute to the mechanistic understanding of the binding of adenine base nucleotides. Based on the kinetic results, it is suggested that the binding of the 5′-nucleotides (AMP, ADP and ATP) takes place in a rapid nucleophile concentration-dependent step, followed by a concentration-independent ring-closure reaction. Kinetic data and activation parameters have been interpreted in terms of an associative mechanism and discussed in reference to the data reported before.

The self-organization of adenosine 5′-triphosphate and adenosine 5′-diphosphate in aqueous solution as determined from ultraviolet hypochromic effects

The self-association of adenosine 5′-triphosphate (ATP) and of adenosine 5′-diphosphate (ADP) was studied in aqueous solution at different pH values, over the concentration range from 5×10 −6 to 5×10 −2 M, by ultraviolet spectroscopy. Measures of the molar absorptivity of the ultraviolet bands of these compounds with increasing concentration have shown two hypochromic effects, at concentrations below 10 −3 and above 10 −3 M, respectively. These results can be interpreted in terms of self-association processes involving the formation of dimers and of polymers. From the fitting of the experimental curves of hypochromic effects, self-association constants for dimerization and polymerization were calculated. The results obtained are discussed in relation to the values reported in the literature and indicate the influence of the concentration range not only on the numerical value but also on the order of magnitude of the association constants. Comparison of ATP with ADP shows that the length of the phosphate chain may be a relevant feature in the nature of the self-organization processes in these adenine nucleotides in aqueous solution.