Steric Effects in the Tuning of the Diastereoselectivity of the Intramolecular Free-Radical Cyclization to an Olefin As Exemplified through the Synthesis of a Carba-Pentofuranose Scaffold

Two free-radical cyclization reactions with the radical at the chiral C4 of the pentose sugar and the intramolecularly C1-tethered olefin (on radical precursors 8 and 17) gave a new diastereospecific C4-C8 bond in dimethylbicyclo[2.2.1]heptane 9, whereas the new C4-C7 bond in 7-methyl-2-oxabicyclo[2.2.1]heptanes 18a/18b gave trans and cis diastereomers, in which the chirality of the C4 center is fully retained as that of the starting material. It has been shown how the chemical nature of the fused carba-pentofuranose scaffolds, dimethylbicyclo[2.2.1]heptane 9 vis-a-vis 7-methyl-2-oxabicyclo[2.2.1]heptanes 18a/18b (C7-Me in the former versus 2-O- in the latter), dictates the stereochemical outcome both at the Grignard reaction step as well as in the free-radical ring-closure reaction. The formation of pure 1,8-trans-bicyclo[2.2.1]heptane 9 from 8 suggests that the boat-like transition state is favored due to the absence of steric clash of the bulky 1(S)-O-p-methoxybenzyl (PMB) and 7(R)-Me substituents (both in the α-face) with that of the 8(R)-CH(2)(?) radical in the β-face. The conversion of 17 → 18a-7(S) and 18b-7(R) in 6:4 ratio shows that the participation of both the chair- and the boat-like transition states is likely.     

Synthesis of 2',4'-propylene-bridged (carba-ENA) thymidine and its analogues: the engineering of electrostatic and steric effects at the bottom of the minor groove for nuclease and thermodynamic stabilities and elicitation of RNase H

2',4'-Propylene-bridged thymidine (carba-ENA-T) and five 8'-Me/NH(2)/OH modified carba-ENA-T analogues have been prepared through intramolecular radical addition to C═N of the tethered oxime-ether. These carba-ENA nucleosides have been subsequently incorporated into 15mer oligodeoxynucleotides (AON), and their affinity toward cDNA and RNA, nuclease resistance, and RNase H recruitment capability have been investigated in comparison with those of the native and ENA counterparts. These carba-ENAs modified AONs are highly RNA-selective since all of them led to slight thermal stabilization effect for the AON:RNA duplex, but quite large destabilization effect for the AON:DNA duplex. It was found that different C8' substituents (at the bottom of the minor groove) on carba-ENA-T only led to rather small variation of thermal stability of the AON:RNA duplexes. We, however, observed that the parent carba-ENA-T modified AONs exhibited higher nucleolytic stability than those of the ENA-T modified counterparts. The nucleolytic stability of carba-ENA-T modified AONs can be further modulated by C8' substituent to variable extents depending on not only the chemical nature but also the stereochemical orientation of the C8' substituents: Thus, (1) 8'S-Me on carba-ENA increases the nucleolytic stability but 8'R-Me leads to a decreased effect; (2) 8'R-OH on carba-ENA had little, if any, effect on nuclease resistance but 8'S-OH resulted in significantly decreased nucleolytic stability; and (3) 8'-NH(2) substituted carba-ENA leads to obvious loss in the nuclease resistance. The RNA strand in all of the carba-ENA derivatives modified AON:RNA hybrid duplexes can be digested by RNase H1 with high efficiency, even at twice the rate of those of the native and ENA modified counterpart.     

The determination of acetaminophen using a carbon nanotube:graphite-based electrode

The oxidation of acetaminophen was studied at a glassy carbon electrode modified with multi-walled carbon nanotubes and a graphite paste. Cyclic voltammety, differential pulse voltammetry and square wave voltammetry at various pH values, scan rates, and the effect of the ratio of nanotubes to graphite were investigated in order to optimize the parameters for the determination of acetaminophen. Square wave voltammetry is the most appropriate technique in giving a characteristic peak at 0.52 V at pH 5. The porous nanostructure of the electrode improves the surface area which results in an increase in the peak current. The voltammetric response is linear in the range between 75 and 2000 ng.mL^?1, with standard deviations between 0.25 and 7.8%, and a limit of detection of 25 ng.mL^?1. The method has been successfully applied to the analysis of acetaminophen in tablets and biological fluids.     

The daily radon dose in body organs caused by drinking milk and water

Milk is considered as the richest nutrition, being used by people. When drinking milk or water the radon gas will transfer from air to them rapidly. Since milk is majorly composed of water, probably radon existence in livestock consumable water could be the main cause of its presence in milk. Different portion of milk changed by radon gamma ray and consumption of radon included water or milk has its effects on the human body. For investigation the effect of radon in water or milk on human organs, this study has been done in two phases with MCNPX software. In the first phase, the dose rate of absorbed gamma ray by different portion of milk which is indoctrinated by 1 Bq/m³ of radon during a day is calculated. Moreover, the effects shown by milk and its components in radon gamma spectrum, which is demonstrator of milk absorption spectrum, are also surveyed. In the second phase as well, according to the human body phantom, the absorbed gamma dose caused by daily consumption of indoctrinated water or milk with 1 Bq/m³ radon is calculated. The production rate of free radicals in milk and its different components are derived according to escape data of MCNPX code.     

Measurement of isomeric yield ratios of the 104m,g,106m,gAg in the 45- and 55-MeV bremsstrahlung induced reactions of natural silver

The isomeric yield ratios for the ^natAg(γ,xn)^{104m,g,106m,g}Ag reactions with the end-point bremsstrahlung energies of 45- and 55-MeV have been determined by the off-line γ-ray spectrometric technique using 100 MeV electron linac at Pohang accelerator laboratory, Korea. The present data were compared with literature data in comparable compound nucleus from the ^natAg(γ,xn), ^natPd(p,xn), and ¹⁰³Rh(α,xn) reactions to examine the effects of an excitation energy and an input angular momentum. It is observed that the isomeric yield ratios of ^104,106Ag in ^natAg(γ,xn), ^natPd(p,xn) and ¹⁰³Rh(α,xn) reactions increase with the end-point bremsstrahlung energy, proton and alpha energy, which indicate the role of excitation energy. It is also found that for the similar compound nucleus at same excitation energy, the isomeric yield ratio of ^104m,gAg is higher in the ^natPd(p,xn) and ¹⁰³Rh(α,xn) reactions than those in ^natAg(γ,xn) reaction, which indicate the effect of an input angular momentum.     

Effect of methyl groups substitution on the strength of intramolecular hydrogen bonding of naphthazarin: DFT and NBO studies

A density functional theory (DFT) study-based method B3LYP/6-311++G** was carried out to investigate the methyl groups substitution effect on the structure and the strength of intramolecular hydrogen bonding in naphthazarin (NZ) (5,8-dihydroxy-1,4-naphthoquinone). The full geometry optimization of molecular structures, the difference between the energies of hydrogen-bonded and non-hydrogen-bonded rotamers, and the proton chemical shift of the hydroxyl groups in NZ and its methyl substituents obtained at the B3LYP/6-311++G** level. The vibrational frequencies of all samples and their deuterated analogues were calculated at the same theoretical level. The ¹H chemical shifts for NZ and its methyl substituents were computed at the B3LYP/6-311++G** level using the gauge-including atomic orbital method. Furthermore, in order to investigate the changes in bond order, electron density, electron delocalization, and steric effects caused by methyl substituents, natural bond orbital analysis were carried out at the B3LYP/6-311++G** level. After comparing these effective parameters in methyl substituents with those of their parent, NZ, we concluded that, in general, intramolecular hydrogen bonding strength increases by substituting methyl groups in the different positions of NZ.     

Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot Spot

The SERS-based detection of protein sequences with single-residue sensitivity suffers from signal dominance of aromatic amino acid residues and backbones, impeding detection of non-aromatic amino acid residues. Herein, we trap a gold nanoparticle in a plasmonic nanohole to generate a single SERS hot spot for single-molecule detection of 2 similar polypeptides (vasopressin and oxytocin) and 10 distinct amino acids that constitute the 2 polypeptides. Significantly, both aromatic and non-aromatic amino acids are detected and discriminated at the single-molecule level either at individual amino acid molecules or within the polypeptide chains. Correlated with molecular dynamics simulations, our results suggest that the signal dominance due to large spatial occupancy of aromatic rings of the polypeptide sidechains on gold surfaces can be overcome by the high localization of the single hot spot. The superior spectral and spatial discriminative power of our approach can be applied to single-protein analysis, fingerprinting, and sequencing.     

Heteropolyacid supported on amine-functionalized halloysite nano clay as an efficient catalyst for the synthesis of pyrazolopyranopyrimidines via four-component domino reaction

An efficient heterogeneous hybrid catalyst was developed by functionalization of halloysite clay nanotubes by γ-aminopropyltriethoxysilane and then immobilization of a Keggin type heteropolyacid, phosphotungstic acid. This hybrid catalyst was characterized by SEM/EDX, FTIR and XRD and its catalytic activity for the synthesis of pyrazolopyranopyrimidine derivatives via four-component domino reaction of barbituric acid, hydrazine hydrate, ethyl acetoacetate and benzaldehyde was investigated. The results indicated that the hybrid system can promote the reaction to afford the desired products in high yields and short reaction times. The superior catalytic activity of this system was confirmed when compared with those reported, previously. Moreover, this novel heterogeneous catalyst was found to be easily separable and recyclable. It was re-used at least three times with negligible loss of activity. Significantly, this protocol can be extended to nonconventional green heating sources such as microwave and ultrasonic irradiations.