Helical structure determines different susceptibilities of dsDNA, dsRNA, and tsDNA to counterion-induced condensation.

Recent studies of counterion-induced condensation of nucleic acid helices into aggregates produced several puzzling observations. For instance, trivalent cobalt hexamine ions condensed double-stranded (ds) DNA oligomers but not their more highly charged dsRNA counterparts. Divalent alkaline earth metal ions condensed triple-stranded (ts) DNA oligomers but not dsDNA. Here we show that these counterintuitive experimental results can be rationalized within the electrostatic zipper model of interactions between molecules with helical charge motifs. We report statistical mechanical calculations that reveal dramatic and nontrivial interplay between the effects of helical structure and thermal fluctuations on electrostatic interaction between oligomeric nucleic acids. Combining predictions for oligomeric and much longer helices, we also interpret recent experimental studies of the role of counterion charge, structure, and chemistry. We argue that an electrostatic zipper attraction might be a major or even dominant force in nucleic acid condensation.

Towards high-performance, low-cost quartz sensors with high-density, well-separated, vertically aligned ZnO nanowires by low-temperature, seed-less, single-step, double-sided growth.

Resonant sensors with nanostructured surfaces have long been considered as an emergent platform for high-sensitivity transduction because of the potentially very large sensing areas. Nevertheless, until now only complex, time-consuming, expensive and sub-optimal fabrication procedures have been described; in fact, especially with reference to in-liquid applications, very few devices have been reported. Here, we first demonstrate that, by immersing standard, ultra-low-cost quartz resonators with un-polished silver electrodes in a conventional zinc nitrate/HMTA equimolar nutrient solution, the gentle contamination from the metallic package allows direct growth on the electrodes of arrays of high-density (up to 10 µm⁻²) and well-separated (no fusion at the roots) ZnO nanowires without any seed layer or thermal annealing. The combination of high-density and good separation is ideal for increasing the sensing area; moreover, this uniquely simple, single-step process is suitable for conventional, ultra-low-cost and high-frequency quartzes, and results in devices that are already packaged and ready to use. As an additional advantage, the process parameters can be effectively optimized by measuring the quartz admittance before and after growth. As a preliminary test, we show that the sensitivity to the liquid properties of high-frequency (i.e. high sensitivity) quartzes can be further increased by nearly one order of magnitude and thus show the highest ever reported frequency shifts of an admittance resonance in response to immersion in both ethanol and water.

Concise NMR approach for molecular dynamics characterizations in organic solids.

Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics.

A robust metal-organic framework constructed from alkoxo-bridged binuclear nodes and hexamethylenetetramine spacers: crystal structure and sorption studies.

A neutral 3D metal-organic framework, (3)(∞)[Cu(2)(mand)(2)(hmt)]·H(2)O (1), was constructed from binuclear Cu(2)O(2) alkoxo-bridged nodes, generated by the doubly deprotonated mandelic acid. The nodes are connected by hexamethylenetetramine (hmt) spacers, which act as biconnective bridging ligands, and by carboxylato groups. Channels are observed along the crystallographic c axis. The water molecules from the channels can be easily removed, preserving the architecture of the crystal, which is stable up to 280 °C. The Langmuir surface area was found to be 610 m(2) g(-1). The sorption ability of 1 was investigated using H(2) and CO(2).

Identifying urotropine derivatives as co-donors of formaldehyde and nitric oxide for improving antitumor therapy.

A pharmacophore integration strategy was utilized to develop the first co-donor of formaldehyde and nitric oxide (FANO), composed of urotropine derived nitramine/nitrosamine. FANO simultaneously generated formaldehyde and nitric oxide on-demand, resulting in synergistic anticancer effects. Importantly, liposomal formulation of FANO effectively inhibited tumor growth with minimal side-effects, providing a potent combined nitric oxide therapy for malignancy.

A simplified mass isotopomer approach to estimate gluconeogenesis rate in vivo using deuterium oxide.

We compare a new simplified (2)H enrichment mass isotopomer analysis (MIA) against the laborious hexamethylentetramine (HMT) method to quantify the contribution of gluconeogenesis (GNG) to total glucose production (GP) in calves. Both methods are based on the (2)H labeling of glucose after in vivo administration of deuterium oxide. The (2)H enrichments of plasma glucose at different C-H positions were measured as aldonitrile pentaacetate (AAc) and methyloxime-trimethylsilyl (MoxTMS) derivatives or HMT by gas chromatography/mass spectrometry (GC/MS). Two pre-ruminating fasted Holstein calves (51 kg body mass, BM, age 7 days) received two oral bolus doses of (2)H(2)O (10 g/kg BM, 70 atom% (2)H) at 7:00 h and 11:00 h after overnight food withdrawal. Blood samples for fractional GNG determination were collected at -24 and between 6 and 9 h after the first (2)H(2)O dose. The ratio of (2)H enrichments C5/C2 represents the contribution of GNG to GP. The (2)H enrichment at C2 was calculated based on the ion fragments at m/z 328 (C1-C6) - m/z 187 (C3-C6) of glucose AAc. The (2)H enrichment at C5 was approximated either by averaging the (2)H enrichment at C5-C6 using the ion fragment of glucose MoxTMS at m/z 205 or by conversion of the C5 of glucose into HMT. The fractional GNG calculated by the C5-C6 average (2)H enrichment method (41.4 +/- 6.9%) compared to the HMT method (34.3 +/- 11.4%) was not different (mean +/- SD, n = 6 replicates). In conclusion, GNG can be estimated with less laborious sample preparation by means of our new C5-C6 average (2)H enrichment method using AAc and MoxTMS glucose derivatives.

Facile and efficient aromatization of 1,4-dihydropyridines with M(NO3)2.XH2O, TNCB, TBAP and HMTAI and preparation of deuterium labeled dehydronifedipine from nifedipine-d3.

The easy and efficient aromatization of various 1,4-dihydropyridines was investigated using various metal nitrates, trinitratocerium(IV) bromate (TNCB), and tetrabutyl ammonium periodate (TBAP) as oxidant in acetic acid at 100 degrees C, as well as hexamethylenetetramine-iodine (HMTAI) reflux in methanol. The efficient conversion of nifedipine-d(3) to dehydronifedipine-d(3) as an internal standard can be used in the measurement of nifedipine concentration in a body.

Structure and binding in crystals of cagelike molecules: hexamine and platonic hydrocarbons.

In this paper, we show that first-principle calculations using a van der Waals density functional (vdW-DF) [M. Dion, H. Rydberg, E. Schroder, D. C. Langreth, and B. I. Lundqvist, Phys. Rev. Lett. 92, 246401 (2004)] permit the determination of molecular crystal structure within density functional theory (DFT). We study the crystal structures of hexamine and the platonic hydrocarbons (cubane and dodecahedrane). The calculated lattice parameters and cohesion energy agree well with experiments. Further, we examine the asymptotic accounts of the van der Waals forces by comparing full vdW-DF with asymptotic atom-based pair potentials extracted from vdW-DF. The character of the binding differs in the two cases, with vdW-DF giving a significant enhancement at intermediate and relevant binding separations. We analyze consequences of this result for methods such as DFT-D and question DFT-D's transferability over the full range of separations.

Preservatives in cosmetics: reactivity of allergenic formaldehyde-releasers towards amino acids through breakdown products other than formaldehyde.

BACKGROUND: Compounds slowly releasing formaldehyde, the so-called formaldehyde-releasers, are commonly employed as preservatives in cosmetics instead of free formaldehyde, which is a strong skin sensitizer. It has been long accepted that formaldehyde-releaser sensitization is attributable to released formaldehyde. However, clinical studies show the existence of patients allergic to formaldehyde-releasers but not to formaldehyde itself. OBJECTIVES: To prove that, for certain formaldehyde-releasers, reactive intermediates other than formaldehyde could be involved in the formation of the hapten-protein antigenic complex, a key step of the sensitization process, thus explaining their sensitizing potential. MATERIALS/METHODS: DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol and methenamine were synthesized, (13) C-labelled at the position(s) precursor of formaldehyde. Their reactivity towards amino acids was followed by one-dimensional and two-dimensional (13) C-nuclear magnetic resonance. RESULTS: Many adducts formed by reacting formaldehyde-releasers with amino acids resulted from a direct interaction of the releaser or from reaction of a breakdown product, and not from a reaction involving simply released formaldehyde. DMDM hydantoin was reactive per se, and 2-bromo-2-nitropropane-1,3-diol and methenamine decomposed in water, producing bromoethanol and diaminomethane, respectively, which were reactive towards some of the amino acids tested. CONCLUSION: The reactivity of distinctive formaldehyde-releasers towards amino acids is not limited to formaldehyde release.

The Production and Potential Detection of Hexamethylenetetramine-Methanol in Space.

Numerous laboratory studies of astrophysical ice analogues have shown that their exposure to ionizing radiation leads to the production of large numbers of new, more complex compounds, many of which are of astrobiological interest. We show here that the irradiation of astrophysical ice analogues containing H2O, CH3OH, CO, and NH3 yields quantities of hexamethylenetetramine-methanol (hereafter HMT-methanol; C7N4H14O) that are easily detectible in the resulting organic residues. This molecule differs from simple HMT, which is known to be abundant in similar ice photolysis residues, by the replacement of a peripheral H atom with a CH2OH group. As with HMT, HMT-methanol is likely to be an amino acid precursor. HMT has tetrahedral (Td) symmetry, whereas HMT-methanol has C1 symmetry. We report the computed expected infrared spectra for HMT and HMT-methanol obtained using ab initio quantum chemistry methods and show that there is a good match between the observed and computed spectra for regular HMT. Since HMT-methanol lacks the high symmetry of HMT, it produces rotational transitions that could be observed at longer wavelengths, although establishing the exact positions of these transitions may be challenging. It is likely that HMT-methanol represents an abundant member of a larger family of functionalized HMT molecules that may be present in cold astrophysical environments.

High-performance immunolatex possessing a mixed-PEG/antibody coimmobilized surface: highly sensitive ferritin immunodiagnostics.

To create a high-performance immunoassay system based on a nanosphere/antibody complex, pentaethylenehexamine-ended poly(ethylene glycol), N6-PEG comprising N6-PEG-5k (M(n) = 6000 g/mol) and N6-PEG-2k (M(n) = 2000 g/mol) was employed as a novel blocking agent to modify the surface of nanospheres. Both the antibody (antiferritin) and the N6-PEG were covalently bonded onto the nanospheres by the linkage of their amino groups with the activated carboxyl groups of those particles. The quantification of antiferritin and tethered N6-PEG polymer was carried out using the copper reduction/bicinchoninic acid reaction (the Micro BCA method). Dynamic-light-scattering (DLS) and electrophoretic mobility (mu(e)) measurements were performed to characterize the nanosphere/antiferritin/N6-PEG complex, which was prepared under various conditions. Simultaneously, the immune response of the complex obtained in this manner was measured by the turbidimetric monitoring method in phosphate buffer (10 mM, pH = 7.4). On the basis of all the results, the optimum conditions for preparing an acceptable nanosphere/antiferritin/N6-PEG complex were determined. Interestingly, compared to the blocking treatment with bovine serum albumin (BSA), which is a well-known blocking agent, surface modification with N6-PEG, especially that using a mixture of N6-PEG-5k and N6-PEG-2k, improved the performance (increased immune response yield and decreased detection limit) of the nanosphere/antiferritin complex to a remarkable degree in both phosphate buffer and 100% fetal bovine serum (FBS), thus significantly demonstrating the potential of the nanosphere/antibody/mixed-PEG complex as central to a high-performance immunoassay system.

Studies on the adsorption property and structure of polyamine-ended poly(ethylene glycol) derivatives on a gold surface by surface plasmon resonance and angle-resolved X-ray photoelectron spectroscopy.

The adsorption properties and structure of polyamine-ended poly(ethylene glycol) (PEG) derivatives on a flat gold surface were studied by means of surface plasmon resonance (SPR) and X-ray photoelectron spectroscopy (XPS) using PEG(5k)-block-poly[2-(N,N-dimethylamino)ethyl methacrylate](7.5k) [PEG-b-PAMA(5k/7.5k)] and pentaethylenhexamine-ended PEG(5k) [N6-PEG(5k)], which had 48 and 6 amino groups at the omega-end, respectively. The SPR analysis showed that the amount of PEG-b-PAMA(5k/7.5k) adsorbed onto the gold surface was not affected by the change in pH, and the desorption of this copolymer from the surface was not observed upon the addition of a solution at high salt concentration. The angle-resolved XPS (ARXPS) analysis revealed the structure of the PEG-b-PAMA polymer layer constructed on the gold surface: the PAMA segments were concentrated and located at the interface between the PEG layer and the gold surface. On the other hand, in the case of the PEG-graft-PAMA copolymer (PAMA-g-PEG)-modified gold surface, both the PAMA and the PEG segments homogeneously migrated to all regions of the constructed copolymer layer. The adsorbed amounts of N6-PEG(5k) under different pH conditions were constant and 2-3 times higher than those caused by the adsorption of single amino group-terminated PEG(5k) [PEG-NH(2)(5k)] and hydroxyl group-terminated PEG(5k) [PEG-OH(5k)]. The N6-PEG(5k)-modified gold surface showed a higher nonfouling property toward the adsorption of bovine serum albumin compared with the bare and the N6-modified gold surface. These results indicate that polyamine-ended PEGs were strongly immobilized onto the gold surface by polyamine anchors, even though electrostatic interaction between the polyamine and the gold substrate was not the dominant factor in this adsorption event. Furthermore, the formation of an almost complete phase-separated PEG/polyamine layer on the gold surface by polyamine-ended PEGs was strongly suggested.

Relationship between solution structure and phase behavior: a neutron scattering study of concentrated aqueous hexamethylenetetramine solutions.

The water-hexamethylenetetramine system displays features of significant interest in the context of phase equilibria in molecular materials. First, it is possible to crystallize two solid phases depending on temperature, both hexahydrate and anhydrous forms. Second, saturated aqueous solutions in equilibrium with these forms exhibit a negative dependence of solubility (retrograde) on temperature. In this contribution, neutron scattering experiments (with isotopic substitution) of concentrated aqueous hexamethylenetetramine solutions combined with empirical potential structure refinement (EPSR) were used to investigate the time-averaged atomistic details of this system. Through the derivation of radial distribution functions, quantitative details emerge of the solution coordination, its relationship to the nature of the solid phases, and of the underlying cause of the solubility behavior of this molecule.

Synthesis, crystal structure and luminescent properties of one coordination polymer of cadmium(II) with mixed thiocyanate and hexamethylenetetramine ligands.

A novel Cd(II) coordination polymer [Cd(SCN)(2)(hmt)(1/2)(H(2)O)](2).H(2)O (hmt=hexamethylenetetramine) has been synthesized and characterized by IR, elemental analysis, TG technique and X-ray crystallography. Cd(II) atom has an distorted octahedral environment with an N(3)S(2)O donor set. Every six Cd(II) centers are linked by hmt and thiocyanato bridges to form a planar 2D coordination polymer containing hexagonal metallocyclic rings [Cd(6)(SCN)(8)(hmt)(2)]. A 2D layer structure is held together with its neighboring ones via a set of hydrogen-bonding interactions to form a 3D supramolecular structure. The luminescent properties of the title complex in the solid state were investigated.

Formaldehyde Release From Personal Care Products: Chromotropic Acid Method Analysis.

BACKGROUND: Preservatives such as formaldehyde and formaldehyde releasers (F/FRs) are found in personal care products. Studies from Europe and Israel have indicated that products with undeclared F/FRs on product labels may have detectable levels of formaldehyde. OBJECTIVE: The aim of the study was to determine the presence of formaldehyde in samples of US personal care products. METHODS: Fifty-four baby and adult products were tested with the chromotropic acid method. A blinded investigator graded the color change as mild, moderate, or strong. RESULTS: All 8 products declaring F/FRs resulted in a deep purple color change, indicating a strong reaction. Of the 46 products with undeclared F/FRs, 4 (8.6%) were found to release formaldehyde. All 4 resulted in a light purple color change, indicating a mild reaction. CONCLUSIONS: Overall, 4 of 54 products (7.4%) had label information, which did not match chromotropic acid method testing results. Clinicians and formaldehyde-allergic individuals should be aware of the limitations of product ingredient labeling in managing allergic contact dermatitis to formaldehyde.

Green protocol for the preparation of hydrophilic molecularly imprinted resin in water for the efficient selective extraction and determination of plant hormones from bean sprouts.

In this study, a novel and green synthesis of a new hydrophilic molecularly imprinted 3-aminophenol-hexamethylenetetramine (MIAPH) resin for the selective recognition and separation of plant hormones was developed. The MIAPH resin was obtained using 3-aminophenol as multifunctional monomer which introduced hydroxyl, amino, and imino groups simultaneously, and adenine was used as a dummy template for molecular imprinting. Meanwhile, hexamethylenetetramine released formaldehyde slowly through hydrolysis which was used as the cross-linking agent to avoid the direct and excessive use of toxic formaldehyde. The entire procedure was performed under mild conditions, and was facile, environmentally friendly and energy-efficient. The obtained MIAPH resin showed high specific recognition toward plant hormones and higher recoveries in bean sprouts compared to NIAPH, HLB, and C18. Various parameters affecting the extraction efficiency were optimized, and the calibration linearity of the MIAPH‒SPE‒HPLC method was determined from 0.07 to 2.86 mg kg-1 with a correlation coefficient (r) ≥ 0.9994 under the optimal conditions. Recoveries of spiked standards ranged from 90.2 to 99.1% for bean sprout with a relative standard deviation of ≤5.3%. Finally, the established MIAPH‒SPE‒HPLC method was successfully applied for the selective extraction and sensitive detection of plant hormones in a variety of complex vegetable matrices.

High-efficacy adsorption of Cr(VI) and anionic dyes onto ß-cyclodextrin/chitosan/hexamethylenetetramine aerogel beads with task-specific, integrated components.

To significantly enhance the adsorption efficacy of hexavalent chromium from aqueous medium, a novel and non-toxic chitosan-based composite beads were prepared by integrating task-specific components into one sample, namely ß-cyclodextrin/chitosan/hexamethylenetetramine (ß-CD-CS@HMTA). The pseudo- second-order kinetic and Langmuir isotherm model was used to describe the adsorption process. The maximum capacity Cr(VI) removal reached 333.8 mg/g which was superior to most of reported CS derivative adsorbents. The sorption mechanism of composite was investigated by employing FT-IR, SEM-EDS and XPS techniques. It showed that the reason for efficient removal of Cr(VI) onto resultant sample including chemisorption and reduction of Cr(VI) to the non-toxic Cr(III), and the two components of ß-CD and HMTA with task-specific had played a crucial role during the adsorption process. Most importantly, for fixed-bed column sorption testing, the breakthrough curves were well fitted by Thomas model under different flow rates (1, 2 and 3 mL/min). Moreover, the ß-CD-CS@HMTA had also manifested perfect adsorption capability towards anionic dyes in initial concentration 500 mg/L. This research indicated that as-fabricated chitosan-based composite beads are promising adsorbents for Cr(VI) and anionic dyes because of its superiority of low-cost, easy regeneration and environmental friendly.

Copper(I) cyanide networks: synthesis, structure, and luminescence behavior. Part 2. Piperazine ligands and hexamethylenetetramine.

A variety of photoluminescent, and in some cases thermochromic, metal-organic networks of CuCN were self-assembled in aqueous reactions with amine ligands: (CuCN) 2(Pip) ( 1a), (CuCN) 20(Pip) 7 ( 1b), (CuCN) 7(MePip) 2 ( 2), (CuCN) 2(Me 2Pip) ( 3a), (CuCN) 4(Me 2Pip) ( 3b), (CuCN) 7(EtPip) 2 ( 4), (CuCN) 4(Et 2Pip) ( 5), (CuCN) 3(BzPip) 2 ( 6a), (CuCN) 5(BzPip) 2 ( 6b), (CuCN) 7(BzPip) 2 ( 6c), (CuCN) 4(BzPip) ( 6d), (CuCN) 2(Bz 2Pip) ( 7), (CuCN)(Ph 2CHPip) ( 8a), (CuCN) 2(Ph 2CHPip) ( 8b), (CuCN) 3(HMTA) 2 ( 9a), (CuCN) 5(HMTA) 2 ( 9b), and (CuCN) 5(HMTA) ( 9c) (Pip = piperazine, MePip = N-methylpiperazine, Me 2Pip = N, N'-dimethylpiperazine, EtPip = N-ethylpiperazine, Et 2Pip = N, N'-diethylpiperazine, BzPip = N-benzylpiperazine, Bz 2Pip = N, N'-dibenzylpiperazine, Ph 2CHPip = N-(diphenylmethyl)piperazine, and HMTA = hexamethylenetetramine). New X-ray structures are reported for 1b, 2, 3b, 4, 5, 6a, 6d, 7, 8b, 9b, and 9c. An important structural theme is the formation of (6,3) (CuCN) 2(piperazine) sheets with or without threading of independent CuCN chains. Strong luminescence at ambient temperature is observed for all but complexes 6 and 7. All luminescent compounds show a broad emission band in the blue region at about 450 nm attributable to metal-to-ligand charge transfer behavior based on the large Stokes shift between excitation and emission maxima. 3, 8, and 9 are thermochromic due to an additional lower energy emission band, which is absent at 77 K.

GMS is superior to PAS for diagnosis of onychomycosis.

BACKGROUND: Onychomycosis is a common cause of deformed nails. Periodic acid-Schiff (PAS) stains are more sensitive than fungal cultures for diagnosing onychomycosis. We performed a retrospective study comparing the use of PAS and Gomori methenamine silver (GMS) stains for histopathologic diagnosis of onychomycosis. METHODS: GMS stains were performed on 20 PAS-positive and 51 PAS-negative cases from nail biopsies with a clinical diagnosis of onychomycosis. The PAS stained slides and GMS stained slides were evaluated for the presence of fungal hyphae. The results were analyzed with McNemar's test. RESULTS: All 20 PAS-positive cases were also positive with GMS stains. Of the 51 PAS-negative cases, GMS stains detected an additional five cases with fungal hyphae. GMS stains were quantitatively superior (p < 0.0253). GMS stains were also qualitatively superior. More fungal hyphae were highlighted and fungal hyphae were more easily recognized on low or medium power magnification. CONCLUSIONS: GMS stains are superior to PAS stains for the routine diagnosis of onychomycosis.