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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Syntheses and in silico pharmacokinetic predictions of glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines and pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines as anti-proliferative agents

New glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines were synthesized by the reaction of respective 5-aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines (1a-d) with glucose, galactose, and xylose in ethanol. Their glycopyranosyl structures were reasoned to be in chair conformations and each have hydrazine moiety in the β-configuration. Also, pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines derivatives were synthesized by the reaction of 1a-d with benzoic acid in the presence of phosphorousoxy chloride or by the reaction with benzaldehyde derivatives followed by cyclization in the presence of bromine. All structures of the compounds were confirmed from their IR, {sup 1}H, {sup 13}C, DPET-135°, {sup 1}H-{sup 1}H COSY, {sup 1}H-{sup 13}C HMQC, {sup 13}C-{sup 1}H HMBC spectra and microanalysis. The synthesized compounds showed inhibition of proliferation of MCF-7 human breast cancer cells with IC{sub 50} values ranging from 0.56 to 8.86 µg/ml. Some of the most active compounds showed acceptable predicted pharmacokinetics and drug-likeness properties. .

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

High-resolution photoelectron spectra of the pyrimidine-type nucleobases

High-resolution photoelectron spectra of the gas phase pyrimidine-type nucleobases, thymine, uracil, and cytosine, were collected using synchrotron radiation over the photon energy range 17 ≤ hν ≤ 150 eV. These data provide the highest resolution photoelectron spectra of thymine, uracil, and cytosine published to date. By comparing integrated regions of the energy dependent photoelectron spectra of thymine, the ionization potentials of the first four ionic states of thymine were estimated to be 8.8, 9.8, 10.3, and 10.8 eV. The thymine data also show evidence for low energy shape resonances in three of the outermost valence electronic states. Comparing the uracil spectrum with the thymine spectrum, the four outermost valence electronic states of uracil likely begin at binding energies 9.3, 9.9, 10.5, and 11.0 eV. High-resolution spectra indicate only one tautomeric form of cytosine contributes significantly to the spectrum with the four outermost valence electronic states beginning at binding energies 8.9, 9.9, 10.4, and 10.85 eV.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2011

Low-energy elastic electron interactions with pyrimidine

We present results of measurements and calculations of elastic electron scattering from pyrimidine in the energy range 3-50 eV. Absolute differential and integral elastic cross sections have been measured using a crossed electron-molecule beam spectrometer and the relative flow technique. The measured cross sections are compared with results of calculations using the well-known Schwinger variational technique and an independent-atom model. Agreement between the measured differential cross sections and the results of the Schwinger calculations is good at lower energies but less satisfactory at higher energies where inelastic channels that should be open are kept closed in the calculations.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2018

Synthesis and study of the azide-tetrazole tautomerism in 2-azido-4-(trifluoromethyl)-6-R-pyrimidines (R = H, 4-ClC{sub 6}H{sub 4})

Azide-tetrazole equilibrium in azidopyrimidines bearing trifluoromethyl group on the example of 2-azidopyrimidines has been studied. The latter were synthesized via nitrosation of 2-hydrazino-4-trifluoromethylpyrimidine and reaction of NaN{sub 3} with 4-trifluoromethyl-2- chloro-6-(4-chlorophenyl)pyrimidine. The tautomeric equilibrium 5-trifluoro methyl tetrazolo[1,5-a]pyrimidine ⇆ 2-azido-4-trifluoromethylpyrimidine was observed in the absence of solvent and in DMSO-d{sub 6} solution, whereas in CDCl{sup 3} only an azide form exists. For 2-azido- 4-trifluoromethyl-6-(4-chlorophenyl)pyrimidine, only an azide isomer was detected in CDCl{sup 3} solution, and in DMSO-d{sub 6} solution it is in equilibrium with 5-(trifluoromethyl)-7-(4-chlorophenyl) tetrazolo[1,5-a]pyrimidine (the tautomer ratio is 99 : 1). Thermodynamic and kinetic parameters of 5-trifluoromethyltetrazolo[1,5-a]pyrimidine ⇆ 2-azido-4-trifluoromethylpyri midine tautomeric rearrangement in DMSO-d{sub 6} for 5-trifluoromethyltetrazolo[1,5-a]pyrimidine were determined using the exchange spectroscopy (EXSY) technique.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Unconventional hydrogen bonding to organic ions in the gas phase: Stepwise association of hydrogen cyanide with the pyridine and pyrimidine radical cations and protonated pyridine

Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes for the stepwise association of HCN molecules with the pyridine and pyrimidine radical cations forming the C{sub 5}H{sub 5}N{sup +·}(HCN){sub n} and C{sub 4}H{sub 4}N{sub 2}{sup +·}(HCN){sub n} clusters, respectively, with n = 1–4. For comparison, the binding of 1–4 HCN molecules to the protonated pyridine C{sub 5}H{sub 5}NH{sup +}(HCN){sub n} has also been investigated. The binding energies of HCN to the pyridine and pyrimidine radical cations are nearly equal (11.4 and 12.0 kcal/mol, respectively) but weaker than the HCN binding to the protonated pyridine (14.0 kcal/mol). The pyridine and pyrimidine radical cations form unconventional carbon-based ionic hydrogen bonds with HCN (CH{sup δ+}⋯NCH). Protonated pyridine forms a stronger ionic hydrogen bond with HCN (NH{sup +}⋯NCH) which can be extended to a linear chain with the clustering of additional HCN molecules (NH{sup +}⋯NCH··NCH⋯NCH) leading to a rapid decrease in the bond strength as the length of the chain increases. The lowest energy structures of the pyridine and pyrimidine radical cation clusters containing 3-4 HCN molecules show a strong tendency for the internal solvation of the radical cation by the HCN molecules where bifurcated structures involving multiple hydrogen bonding sites with the ring hydrogen atoms are formed. The unconventional H-bonds (CH{sup δ+}⋯NCH) formed between the pyridine or the pyrimidine radical cations and HCN molecules (11–12 kcal/mol) are stronger than the similar (CH{sup δ+}⋯NCH) bonds formed between the benzene radical cation and HCN molecules (9 kcal/mol) indicating that the CH{sup δ+} centers in the pyridine and pyrimidine radical cations have more effective charges than in the benzene radical cation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

Highlights: Black-Right-Pointing-Pointer We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. Black-Right-Pointing-Pointer Disruption of the cpsII gene significantly reduced the growth of epimastigotes. Black-Right-Pointing-Pointer In particular, the CPSII-null mutant severely retarded intracellular growth. Black-Right-Pointing-Pointer The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Capturing CO 2 in Quadrupolar Binding Pockets: Broadband Microwave Spectroscopy of Pyrimidine-(CO 2 ) n , n = 1,2

Pyrimidine has two in-plane CH(δ+)/N̈(δ–)/CH(δ+) binding sites that are complementary to the (δ–/2δ+/δ–) quadrupole moment of CO 2 . For this study, we recorded broadband microwave spectra over the 7.5–17.5 GHz range for pyrimidine-(CO 2 ) n with n = 1 and 2 formed in a supersonic expansion. Based on fits of the rotational transitions, including nuclear hyperfine splitting due to the two 14 N nuclei, we have assigned 313 hyperfine components across 105 rotational transitions for the n = 1 complex and 208 hyperfine components across 105 rotational transitions for the n = 2 complex. The pyrimidine-CO 2 complex is planar, with CO 2 occupying one of the quadrupolar binding sites, forming a structure in which the CO 2 is stabilized in the plane by interactions with the C–H hydrogens adjacent to the nitrogen atom. This structure is closely analogous to that of the pyridine-CO 2 complex studied previously by (Doran, J. L. J. Mol. Struct. 2012, 1019, 191–195). The fit to the n = 2 cluster gives rotational constants consistent with a planar cluster of C 2v symmetry in which the second CO 2 molecule binds in the second quadrupolar binding pocket on the opposite side of the ring. The calculated total binding energy in pyrimidine-CO 2 is –13.7 kJ mol –1 , including corrections for basis set superposition error and zero-point energy, at the CCSD(T)/ 6-311++G(3df,2p) level, while that in pyrimidine-(CO 2 ) 2 is almost exactly double that size, indicating little interaction between the two CO 2 molecules in the two binding sites. The enthalpy, entropy, and free energy of binding are also calculated at 300 K within the harmonic oscillator/rigid-rotor model. This model is shown to lack quantitative accuracy when it is applied to the formation of weakly bound complexes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Effect of pressure on heterocyclic compounds: Pyrimidine and s-triazine

We have examined the high-pressure behaviors of six-membered heterocyclic compounds of pyrimidine and s-triazine up to 26 and 26.5 GPa, respectively. Pyrimidine crystallizes in Pna2{sub 1} symmetry (phase I) with the freezing pressure of 0.3 GPa, and transforms to another phase (phase II) at 1.1 GPa. Raman spectra of several compression-decompression cycles demonstrate there is a critical pressure of 15.5 GPa for pyrimidine. Pyrimidine returns back to its original liquid state as long as the highest pressure is below 15.1 GPa. Rupture of the aromatic ring is observed once pressure exceeds 15.5 GPa during a compression-decompression cycle, evidenced by the amorphous characteristics of the recovered sample. As for s-triazine, the phase transition from R-3c to C2/c is well reproduced at 0.6 GPa, in comparison with previous Raman data. Detailed Raman scattering experiments corroborate the critical pressure for s-triazine may locate at 14.5 GPa. That is, the compression is reversible below 14.3 GPa, whereas chemical reaction with ring opening is detected when the final pressure is above 14.5 GPa. During compression, the complete amorphization pressure for pyrimidine and s-triazine is identified as 22.4 and 15.2 GPa, respectively, based on disappearance of Raman lattice modes. Synchrotron X-ray diffraction patterns and Fourier transform infrared spectra of recovered samples indicate the products in two cases comprise of extended nitrogen-rich amorphous hydrogenated carbon (a-C:H:N)

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Oral administration of indole substituted dipyrido[2,3-d]pyrimidine derivative exhibits anti-tumor activity via inhibiting AKT and ERK1/2 on hepatocellular carcinoma

Highlights: • Multicomponent reaction (MCR) is a productive and economical method for the synthesis of antitumor compounds by connecting functional moieties. • A series of indole substituted dihydropyrido[2,3-d]pyrimidines were synthesized by MCR. • 4p exhibits antitumor activity both in vitro and in vivo via inhibiting AKT and ERK1/2 pathways on hepatocellular carcinoma. Development of an effective and safe anti-cancer drug is an urgent request for hepatocellular carcinoma (HCC). In this study, we synthesized a series of novel indole substituted dihydropyrido[2,3-d]pyrimidines through the multicomponent reactions to connect pyrido[2,3-d]pyrimidine and indole moities via an one-pot three-component reaction of 3-cyanoacetyl indoles 1, various aromatic aldehyde 2, and 2,6-diaminopyrimidin-4(3H)-one 3. Subsequently, we screened their cytotoxicity via CCK-8 assay in HepG2 cells, a human hepatoma cell line and chose compound 4p that showed the lowest dosage of IC50 to study the antitumor activities to HCC. Interestingly, 4p significantly induced the cell cycle arrest and apoptosis of HepG2 via targeting AKT and ERK1/2 signaling pathways in vitro. To improve the solubility of compound 4p, we hosted this compound into the substituted glucopyranose ring of (2-Hydroxypropyl)-β-cyclodextrin (HBC), a cosolvent approved by FDA with the help of ultrasonication and heating. Finally, we showed that oral administration of HBC-hosted 4p effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice in subcutaneously xenografted model. These results suggest that multicomponent reactions connecting pyrido[2,3-d]pyrimidine and indole moities is a productive and economical method for the synthesis of anticancer compound, and oral administration of HBC-hosted 4p is an effective and safe agents for treatment of HCC, whose clinical application potency warrant further studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Computational Chemistry-Guided Design of Selective Chemoresponsive Liquid Crystals Using Pyridine and Pyrimidine Functional Groups

Computational chemistry-guided designs of chemoresponsive liquid crystals (LCs) with pyridine or pyrimidine groups that bind to metal-cation-functionalized surfaces to provide improved selective responses to targeted vapor species (dimethylmethylphosphonate (DMMP)) over nontargeted species (water) are reported. The LC designs against experiments are tested by synthesizing 4-(4-pentyl-phenyl)-pyridine and 5-(4-pentyl-phenyl)-pyrimidine and quantifying LC responses to DMMP and water. Consistent with the computations, pyridine-containing LCs bind to metal-cation-functionalized surfaces too strongly to permit a response to either DMMP or water whereas pyrimidine-containing LCs undergo a surface-driven orientational transition in response to DMMP without interference from water. The computation predictions are not strongly dependent on assumptions regarding the degree of coordination of the metal ions but are limited in their ability to predict LC responses when using cations with mostly empty d orbitals. Overall, this work identifies a promising new class of chemoresponsive LCs based on pyrimidine that exhibits enhanced tolerance to water, a result that is important because water is a ubiquitous and particularly challenging chemical interferent in chemical sensing strategies based on LCs. The work also provides further evidence of the transformative utility of computational chemistry methods to design LC materials that exhibit selective orientational responses in specific chemical environments.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2013

Pyrimidine homeostasis is accomplished by directed overflow metabolism

Cellular metabolism converts available nutrients into usable energy and biomass precursors. The process is regulated to facilitate efficient nutrient use and metabolic homeostasis. Feedback inhibition of the first committed step of a pathway by its final product is a classical means of controlling biosynthesis. In a canonical example, the first committed enzyme in the pyrimidine pathway in Escherichia coli is allosterically inhibited by cytidine triphosphate. The physiological consequences of disrupting this regulation, however, have not been previously explored. Here we identify an alternative regulatory strategy that enables precise control of pyrimidine pathway end-product levels, even in the presence of dysregulated biosynthetic flux. The mechanism involves cooperative feedback regulation of the near-terminal pathway enzyme uridine monophosphate kinase. Such feedback leads to build-up of the pathway intermediate uridine monophosphate, which is in turn degraded by a conserved phosphatase, here termed UmpH, with previously unknown physiological function. Such directed overflow metabolism allows homeostasis of uridine triphosphate and cytidine triphosphate levels at the expense of uracil excretion and slower growth during energy limitation. Disruption of the directed overflow regulatory mechanism impairs growth in pyrimidine-rich environments. Thus, pyrimidine homeostasis involves dual regulatory strategies, with classical feedback inhibition enhancing metabolic efficiency and directed overflow metabolism ensuring end-product homeostasis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C{sub 4}H{sub 4}N{sub 2}) in H{sub 2}O-rich ice mixtures that contain NH{sub 3}, CH{sub 3}OH, or CH{sub 4} leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H{sub 2}O, CH{sub 3}OH, and NH{sub 3}, with or without CH{sub 4}, to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

79 ASTRONOMY AND ASTROPHYSICS↗