Retention Behavior of Nucleic Acid Bases and Purine Derivatives on Titania

The retention of nucleic acid bases and purine derivatives on titania was studied using a 0.4 mM acetic acid–sodium acetate buffer (pH 6.0) and 70% aqueous methanol as mobile phases. We observed that the retention strength of tested analytes on titania was dependent on the structural differences between pyrimidine and purine skeletons and the variety and number of substituents. The retention order was purine derivatives with methyl groups, pyrimidine bases and purine derivatives with hydrophilic functional groups, which were retained most strongly on titania. We concluded that the retention of each analyte was caused by the analyte’s hydrophobicity in the case of purine derivatives with methyl groups and pyrimidine bases. In the case of purine and its derivatives with hydrophilic functional groups, it was considered that the retention was dependent on the analyte’s ability to form chelates, and the variety and number of functional groups on C6 and C2.     

Relationship between retention and molecular structure of pyrimidine bases

Summary The influence of the type and position of CH₃, NH₂ and OH groups in the pyrimidine ring, the eluent composition and the surface chemistry of the stationary phase on the retention of pyrimidine bases in reversed-phase liquid chromatography was investigated. On the basis of the hypothesis about the additivity of the adsorption energy the contribution of various structural groups on retention has been established.     

Double dative bond configuration: pyrimidine on Ge(100)

The adsorption of pyrimidine onto Ge(100) surfaces has been investigated using real-time scanning tunneling microscopy (STM), temperature-programmed desorption (TPD), and density-functional theory (DFT) calculations. Our results show that the adsorbed pyrimidine molecules are tilted about 40 degrees with respect to the Ge surface, and through a Lewis acid-base reaction form bridges between the down-Ge atoms of neighboring Ge dimer rows by double Ge-N dative bonding without loss of aromaticity. For coverages of pyrimidine up to 0.25 ML, a well-ordered c(4x2) structure results from states that appear in STM micrographs as oval-shaped protrusions, which correspond to pyrimidine molecules datively adsorbed on every other dimer. However, above 0.25 ML, the oval-shaped protrusions gradually change into brighter zigzag lines. At 0.50 ML, a p(2x2) structure results from the states that appear in STM as zigzag lines. The zigzag lines are formed by the attachment of pyrimidine molecules to the down-Ge atoms of every Ge dimer. However, the unstable p(2x2) structure eventually reconstructs into a c(4x2) structure due to steric hindrance between the adsorbed pyrimidine molecules after stopping the exposure of pyrimidine to the surface.     

FT-IR Spectroscopic Investigation of Adsorption of Pyrimidine on Sepiolite and Montmorillonite from Anatolia

The adsorption of pyrimidine (PM) on natural montmorillonite and sepiolite from Turkey was investigated by FT-IR spectroscopy. The intercalation of PM within montmorillonite has been shown by X-ray diffraction to increase the interlayer spacing. The spectroscopic results indicate that PM molecules adsorbed on sepiolite are coordinated to Lewis acidic centers or surface hydroxyls by H-bonding interaction through one of the pyrimidine ring nitrogen lone pairs. Moreover, some of the adsorbed PM molecules may enter the interior channels of the sepiolite structure and replace zeolitic water. The intercalated PM molecules within montmorillonite are coordinated to exchangeable cations directly or indirectly through water bridges.     

Structures, energetics and vibrational frequency shifts of hydrated pyrimidine

More than 70 unique micro-hydrated structures of pyrimidine, ranging in size from 1 to 7 water molecules, have been characterized with the B3LYP density functional and the 6-311++G(2df,2pd) triple-ζ split-valence basis set. Explicitly correlated MP2-F12 single-point computations were performed on each structure with a correlation consistent triple-ζ basis set to estimate the relative and dissociation energies at the MP2 complete basis set (CBS) limit. Many of these new structures have significantly lower energies than those previously reported (by as much as 12.66 kcal?mol(-1)). For clusters with 1 and 2 water molecules, the MP2-F12 relative and dissociation energies are virtually identical to the corresponding CCSD(T)-F12 values. As the number of hydrating waters increases, the structures in which the water molecules are clustered together at one of the N atoms have lower energies than those where the water molecules are more distributed around the pyrimidine ring. Micro-hydrated structures that effectively extend the low-energy hydrogen-bonding motifs to both sides of the ring, as would be expected in the bulk phase, reproduce the experimentally observed vibrational frequency shifts of ν(1) and ν(8b) in very dilute aqueous pyrimidine solutions to within 1 cm(-1) . Micro-hydrated structures of pyrimidine in which water molecules are clustered together have lower energies than structures in which the water molecules are more evenly spread around the pyrimidine ring.     

Application of the collision-complex model to collision-induced intersystem crossing and collisional magnetic quenching of polyatomic molecules

The purpose of this paper is to apply the collision-complex model to collision-induced intersystem crossing in poly-atomic molecules (glyoxal, propynal, pyrimidine, etc.), and to the collisional magnetic quenching of polyatomic molecules, with particular emphasis on glyoxal.     

The Effect of Solvation on Electron Attachment to Pure and Hydrated Pyrimidine Clusters

The interaction of low‐energy electrons with biomolecules plays an important role in the radiation‐induced alteration of biological tissue at the molecular level. At electron energies below 15 eV, dissociative electron attachment is one of the most important processes in terms of the chemical transformation of molecules. So far, a common approach to study processes at the molecular level has been to carry out investigations with single biomolecular building blocks like pyrimidine as model molecules. Electron attachment to single pyrimidine, as well as to pure clusters and hydrated clusters, was investigated in this study. In striking contrast to the situation with isolated molecules and hydrated clusters, where no anionic monomer is detectable, we were able to observe the molecular anion for the pure clusters. Furthermore, there is evidence that solvation effectively prevents the ring fragmentation of pyrimidine after electron capture.     

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.     

Colourimetric and spectroscopic discrimination between nucleotides and nucleosides using para-sulfonato-calix[4]arene capped silver nanoparticles

The complexation of nucleosides and nucleotides by hybrid nanoparticles capped by para-sulfonato-calix[4]arene shows clear discrimination between purine and pyrimidine based molecules. For the pyrimidine nucleotides there is appearance of a new absorption band around 550 nm, and a colour change from yellow to orange red and pink.     

Are isolated nucleic acid bases really planar? A Car-Parrinello molecular dynamics study

Car-Parrinello molecular dynamics simulations of the flexibility of isolated DNA bases have been carried out. The comparison of lowest ring out-of-plane vibrations calculated by using MP2/cc-pvdz and BLYP/PW methods reveals that the DFT method with the plane wave basis set reasonably reproduces out-of-plane deformability of the pyrimidine ring in nucleic acid bases and could be used for reliable modeling of conformational flexibility of nucleobases. The conformational phase space of pyrimidine rings in thymine, cytosine, guanine, and adenine has been investigated by using the ab initio Car-Parrinello molecular dynamics method. It is demonstrated that all nucleic acid bases are highly flexible molecules and possess a nonplanar effective conformation of the pyrimidine ring despite the fact that the planar geometry corresponds to a minimum on the potential energy surface. The population of the planar geometry of the pyrimidine ring does not exceed 30%. Among the nonplanar conformations of the pyrimidine rings, the boat-like and half-chair conformations are the most populated.     

Chromatographic Characteristics of Pva Column

Abstract

The retention behavior of polyethylene glycols, carbohydrates, peptides and pyrimidine and purine bases on a newly developed PVA gel column was examined. It has been found that separation was governed by a combined mode consisting of several known factors and dependent on the type of the sample and the nature of the eluent.     

PHOTOCHEMICAL REACTIONS OF AROMATIC KETONES WITH NUCLEIC ACIDS AND THEIR COMPONENTS I—. PURINE AND PYRIMIDINE BASES AND NUCLEOSIDES*.

Abstract— The photochemical reactions of benzophenone and acetophenone with purine and pyrimidine derivatives in aqueous solutions have been investigated by flash photolysis and steady-state experiments. Upon excitation of these two ketones in aqueous solutions, two transient species are observed: molecules in their triplet state and ketyl radicals. The triplet state lifetimes are 65 μsec for benzophenone and 125 μsec for acetophenone. The ketyl radicals disappear by a second order reaction, controlled by diffusion. In the presence of pyrimidine derivatives, the triplet state is quenched and the ketyl radical concentration is decreased without any change in its kinetics of disappearance. Ketone molecules in their triplet state react with purine derivatives leading to an increase in the yield of ketyl radicals due to H-atom abstraction from the purines. Steady-state experiments show that benzophenone and acetophenone irradiated in aqueous solution at wavelengths longer than 290 nm undergo photochemical reactions. The rate of these photochemical reactions is increased in the presence of pyrimidine derivatives and even more in the presence of purine derivatives. Following energy transfer from the triplet state of benzophenone to diketopyrimidines, cyclobutane dimers are formed. The energy transfer rate decreases in the order orotic acid > thymine > uracil. Benzophenone molecules in their triplet state can also react chemically with pyrimidine derivatives to give addition photoproducts. All these results are discussed with respect to photosensitized reactions in nucleic acids involving ketones as sensitizers.     

Studies on separation mechanisms of biological molecules on a polyvinyl alcohol column

Summary The chromatographic separation mechanism on a polyvinyl alcohol (PVA) column in aqueous systems was explored utilizing several different types of compound such as polyethylene glycols, carbohydrates, pyrimidine and purine bases, fatty acids, monophosphate nucleotides and glycyl-peptides. Two types of separation mechanisms were found to occur for these substrates. The polyethylene glycols and the carbohydrates were eluted by size-exclusion chromatography. The retention behavior of the other substrates could be explained by the solvophobic theory, suggesting that the predominant separation mode was reversed-phase chromatography. The occurrence of reversed-phase chromatography was also indicated by the remarkable effect of the addition of ion-association reagents to the chromatographic system on the retention of the monophosphate nucleotides.     

Structural regularities governing sorption and gas chromatographic retention of aromatic nitrogen-containing heterocyclic compounds

The regularities governing differences in the gas chromatographic retention indices of aromatic nitrogen-containing heterocyclic compounds were studied during gas chromatographic analysis on a nonpolar capillary column. The retention indices of pyrrole, pyrazole, imidazole, 1,2,4-triazole, oxazole, thiazole, isoxazole, pyridine, pyridazine, pyrimidine, pyrazine, ands-triazine and their alkyl derivatives depend on the number, nature, and arrangement of heteroatoms and alkyl groups in the cycles. The majority of homologous series ofn-alkyl-substituted azoles and azines andn-alkylbenzenes is characterized by anomalously high differences between the retnetion indices of ethyl and methyl homologs. A scheme of calculation of retention indices of aromatic heterocyclic compounds from increments of heteroatoms was proposed.     

Reversed-phase high-performance liquid chromatography of pyrimidine bases and nucleosides. Application of solvophobic theory

The chromatographic behaviour of some natural and modified pyrimidine bases and nucleosides on an octadecyl stationary phase was studied. The retention and selectivity parameters of the separation of the compounds studied were derived on the basis of solvophobic theory. The mechanism of base and nucleoside interactions with the surface of the hydrocarbonaceous stationary phase is discussed. The best separation is observed at pH 3.5 for the bases and at pH 4.8-5.2 for the nucleosides. An increase in the solute surface tension results in an increased selectivity of separation. When the surface tension and the ionic strength of the mobile phase are not kept constant, there are considerable deviations in retention from that predicted by solvophobic theory.     

Pyrimidine Derivatives with Terminal Pyridyl Heterocycles: Facile Synthesis and Their Antiproliferative Activities

Incorporation of heterocyclic pyrimidine or pyridine motifs is common in the drug design for various therapeutic applications. Herein, we describe the facile synthesis of two molecules containing both pyrimidine and pyridine scaffolds. A variety of analytical techniques (multinuclear NMR, Fourier transform infrared, and mass spectrometry analyses) confirmed the purity of these molecules. In pristine form, their potential as antitumor drugs was screened by investigating their cytotoxicity against various cell lines (cancerous and normal cells). Experimental results confirmed that the two molecules exhibited cell growth inhibition at very low concentrations. This was evident from their IC₅₀ values that are in the range of 0.45–2.20 μM.     

Fast separation of pyrimidine derivatives by capillary electrochromatography on ion-exchange/reversed-phase mixed-mode stationary phases

This work describes the use of mixed-mode stationary phases which exhibit both strong ion-exchange (either cation-exchange, SCX, or anion-exchange, SAX) and reversed-phase chromatographic characteristics in capillary electrochromatographic separations of pyrimidine derivatives. Different packing materials, namely C6, SCX/C6 and SAX/C6, were compared and the influence of the composition of the carrier electrolyte (concentration of acetonitrile and pH) on the retention behavior of the selected solutes was investigated. A separation of all eight pyrimidine derivatives could be obtained on a 6.5 cm column packed with the SAX/C6 stationary phase in less than 3 min, with good peak shapes and efficiencies in the range 39,000 to 81,000 plates per meter.     

Five cases of beta-ureidopropionase deficiency detected by GC/MS analysis of urine metabolome

The clinical presentation of inborn errors of pyrimidine degradation varies considerably from asymptomatic to severe neurological illness. We have reported a method to screen for and make a chemical diagnosis of beta-ureidopropionase deficiency, leading to the discovery of the first asymptomatic case of this disease. In this method, the recovery of beta-ureidopropionate and beta-ureidoisobutyrate, the key biomarkers, was very high,and the adoption of GC/MS and targeted analysis enabled us to simultaneously obtain information related and unrelated to pyrimidine metabolism. The present study reports the results of a large-scale screening of 24,000 newborns using dried urine on filter paper. Identification of a total of four asymptomatic patients among newborns suggests the high incidence (1/6000) of this disease in Japan. While these newborns were asymptomatic, two additional cases detected at the age of 5 years as well as 3 months with this method for high-risk screening had autism and West syndrome, respectively.The key biomarkers and alpha-ureidobutyrate used as an internal standard were found to give not only their di-trimethylsilyl derivatives but also tri-trimethylsilyl derivatives, upon derivatization. The mass spectra and retention times of their tri-trimethylsilyl derivatives and data handling for quantification of the markers are presented.Identification of individuals with defects in pyrimidine metabolism would realize personalized medication in cancer chemotherapy with pyrimidine analogs such as 5-fluorouracil.     

Hydrogen‐bonding and C—H⋯π interactions in 7‐hydroxy‐3‐methoxy‐4‐methyl‐5,6,7,8‐tetrahydro­pyrido­[1,2‐c]pyrimidin‐1(9H)‐one

In the title compound, C₁₀H₁₄N₂O₃, a pyrimidine ring is fused with a piperidine ring. The pyrimidine ring is planar, whereas the piperidine ring adopts a half‐chair conformation. The molecules of the title compound are connected via O—H⋯O intermolecular hydrogen bonds into infinite zigzag chains. The pyrimidine ring is involved in three C—H⋯π interactions, which link the hydrogen‐bonded chains into a three‐dimensional framework.