A novel RNA motif based on the structure of unusually stable 2',5'-linked r(UUCG) loops

We have recently shown that hairpins containing 2',5'-linked RNA loops exhibit superior thermodynamic stability compared to native hairpins comprised of 3',5'-RNA loops [Hannoush, R. N.; Damha, M. J. J. Am. Chem. Soc. 2001, 123, 12368-12374]. A remarkable feature of the 2',5'-r(UUCG) tetraloop is that, unlike the corresponding 3',5'-linked tetraloop, its stability is virtually independent of the hairpin stem composition. Here, we determine the solution structure of unusually stable hairpins of the sequence 5'-G(1)G(2)A(3)C(4)-(U(5)U(6)C(7)G(8))-G(9)(U/T(10))C(11)C(12)-3' containing a 2',5'-linked RNA (UUCG) loop and either an RNA or a DNA stem. The 2',5'-linked RNA loop adopts a new fold that is completely different from that previously observed for the native 3',5'-linked RNA loop. The 2',5'-RNA loop is stabilized by (a). U5.G8 wobble base pairing, with both nucleotide residues in the anti-conformation, (b). extensive base stacking, and (c). sugar-base and sugar-sugar contacts, all of which contribute to the extra stability of this hairpin structure. The U5:G8 base pair stacks on top of the C4:G9 loop-closing base pair and thus appears as a continuation of the stem. The loop uracil U6 base stacks above U5 base, while the cytosine C7 base protrudes out into the solvent and does not participate in any of the stabilizing interactions. The different sugar pucker and intrinsic bonding interactions within the 2',5'-linked ribonucleotides help explain the unusual stability and conformational properties displayed by 2',5'-RNA tetraloops. These findings are relevant for the design of more effective RNA-based aptamers, ribozymes, and antisense agents and identify the 2',5'-RNA loop as a novel structural motif.     

Synthesis of Dihydropyridine Derivatives under Eco‐friendly Approach and Investigation of Cytotoxic Activity

In an effort for development of innovative biologically active agents, a sequence of 1,4‐dihydropyridine analogues was synthesized through the green synthetic method. In addition, all compounds were evaluated for their cytotoxic activities against three human cancer cell lines and mouse melanoma and figured out the most active compounds. Besides, promoter reusability, easy handling of the chemical reagent, simple reaction process, time minimization, ethanol–water solvent compatibility, and cost reduction reagent are key tools for this fruitful path. Thus, these examinations recommended that dihydropyridine and their derivatives are motivating moieties for the discovery of new anticancer drugs.     

Quasi-harmonic approximation of thermodynamic properties of ice Ih, II, and III

Several thermodynamic properties of ice Ih, II, and III are studied by a quasi-harmonic approximation and compared to results of quantum path integral and classical simulations. This approximation allows to obtain thermodynamic information at a fraction of the computational cost of standard simulation methods, and at the same time permits studying quantum effects related to zero-point vibrations of the atoms. Specifically, we have studied the crystal volume, bulk modulus, kinetic energy, enthalpy, and heat capacity of the three ice phases as a function of temperature and pressure. The flexible q-TIP4P/F model of water was employed for this study, although the results concerning the capability of the quasi-harmonic approximation are expected to be valid independently of the employed water model. The quasi-harmonic approximation reproduces with reasonable accuracy the results of quantum and classical simulations showing an improved agreement at low temperatures (T< 100 K). This agreement does not deteriorate as a function of pressure as long as it is not too close to the limit of mechanical stability of the ice phases.     

Solvation free energies calculated using the GB/SA model: Sensitivity of results on charge sets,protocols, and force fields

The sensitivity of aqueous solvation free energies (SFEs), estimated using the GB/SA continuum solvent model, on charge sets, protocols, and force fields, was studied. Simple energy calculations using the GB/SA solvent model were performed on 11 monofunctional organic compounds. Results indicate that calculated SFEs are strongly dependent on the charge sets. Charges derived from electrostatic potential fitting to high level ab initio wave functions using the CHELPG procedure and “class IV” charges from AM1/CM1a or PM3/CM1p calculations yielded better results than the corresponding Mulliken charges. Calculated SFEs were similar to MC/FEP energies obtained in the presence of explicit TIP4P water. Further improvements were obtained by using GVB/6-31G** and MP2/6-31+G** (CHELPG) charge sets that included correlation effects. SFEs calculated using charge sets assigned by the OPLSA* force field gave the best results of all standard force fields (MM2*, MM3*, MMFF, AMBER*, and OPLSA*) implemented in MacroModel. Comparison of relative and absolute SFEs computed using either the GB/SA continuum model or MC/FEP calculations in the presence of explicit TIP4P water showed that, in general, relative SFEs can be estimated with greater accuracy. A second set of 20 mono- and difunctional molecules was also studied and relative SFEs estimated using energy minimization and thermodynamic cycle perturbation (TCP) protocols. SFEs calculated from TCP calculations using the GB/SA model were sensitive to bond lengths of dummy bonds (i.e., bonds involving dummy atoms). In such cases, keeping the bond lengths of dummy bonds close to the corresponding bond lengths of the starting structures improved the agreement of TCP-calculated SFEs with energy minimization results. Overall, these results indicate that GB/SA solvation free energy estimates from simple energy minimization calculations are of similar accuracy and value to those obtained using more elaborate TCP protocols. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 769–780, 1998     

Palladium(II)‐catalyzed catalytic aminocarbonylation and alkoxycarbonylation of terminal alkynes: regioselectivity controlled by the nucleophiles

The aminocarbonylation and alkoxycarbonylation reactions of terminal alkynes took place smoothly and efficiently using a catalyst system Pd(OAc)₂–dppb–p‐TsOH? CH₃CN? CO under relatively mild experimental conditions. The catalytic system was tested and optimized using two different nucleophiles: alcohols and amines. Phenylacetylene (1a) was considered as an alkyne along with diisobutylamine (2b₁) and methanol (2c₁) as nucleophiles. The results showed significant differences in the conversion of 1a and in the selectivity towards the gem or trans unsaturated esters or amides with these nucleophiles. The effects of the type of palladium catalysts, the type of ligands, the amount of dppb and the solvents were carefully studied. With diisobutylamine (2b₁), excellent regioselectivity towards the 2‐acrylamides (gem isomer, 3ab₁) was almost always observed, while trans‐α,β‐unsaturated esters 4ac₁ was the predominant product with methanol (2c₁) as a nucleophile. This remarkable sensitivity in the selectivity of the reaction indicates two different possible mechanistic pathways for these carbonylation reactions. Copyright © 2009 John Wiley & Sons, Ltd.     

Ab initio quantum mechanics-based free energy perturbation method for calculating relative solvation free energies

A free energy perturbation (FEP) method was developed that uses ab initio quantum mechanics (QM) for treating the solute molecules and molecular mechanics (MM) for treating the surroundings. Like our earlier results using AM1 semi empirical QMs, the ab initio QM/MM-based FEP method was shown to accurately calculate relative solvation free energies for a diverse set of small molecules that differ significantly in structure, aromaticity, hydrogen bonding potential, and electron density. Accuracy was similar to or better than conventional FEP methods. The QM/MM-based methods eliminate the need for time-consuming development of MM force field parameters, which are frequently required for drug-like molecules containing structural motifs not adequately described by MM. Future automation of the method and parallelization of the code for Linux 128/256/512 clusters is expected to enhance the speed and increase its use for drug design and lead optimization.     

Spectrophotometric determination of dopamine in pharmaceutical formulations

A new spectrophotometric method was developed for the estimation of dopamine. The method is based on the bromination of the dopamine with a solution of excess brominating mixture. After bromination, the excess brominating mixture is treated with potassium iodide to produce a yellow solution. The absorbance of yellow solution was measured at 350 nm on a Spectronic 1001 spectrophotometer against distilled water as a blank.From Zhurnal Analiticheskoi Khimii, Vol. 60, No. 3, 2005, pp. 2842285.Original English Text Copyright © 2005 by Rami Reddy, Sreedevi, Prabhavathi, Chakravarthy.This article was submitted by the authors in English.     

A silica-supported palladium-bis(oxazoline) complex efficiently catalyzes the synthesis of cinnamic acid derivatives via Mizoroki–Heck coupling reactions

A palladium(II)-bis(oxazoline) complex supported on silica (Pd-BOX-Si) was prepared, characterized and applied as a catalyst in Mizoroki–Heck cross-coupling reactions. The bis(oxazoline) (BOX) ligand has a hydroxyl group that can be anchored to 4-benzyl chloride-functionalized silica gel, followed by the coordination of palladium(II) chloride. The catalytic activity and the recyclability of Pd-BOX-Si have been investigated in the production of cinnamic acid derivatives via Mizoroki–Heck coupling reactions of acrylates with aryl halides; The Pd-BOX-Si catalyst demonstrated excellent catalytic activity. Characterization of the recycled Pd-BOX-Si catalyst revealed its good stability under the reaction conditions employed.     

Reactivity ratios of ethyl acrylate,n-butyl methacrylate copolymer system by 1H-NMR

Ethyl acrylate (EA) and n-butyl methacrylate (n-BMA) copolymers were prepared in solution and the composition of the copolymer samples was estimated by ¹H-NMR spectroscopic techniques. Because the characteristic signals, which vary with the composition of the copolymer, were absent, the ratio of intensities of down-field protons to that of the total protons was used for the estimation of copolymer composition. Reactivity ratios were calculated from these values by using the Kelen-Tudos differential linear equation.     

Few nucleon transfer versus fragmentation in the production of projectile-like fragments in the40Ar+68Zn reaction at 27.6 MeV/nucleon

The isotope distributions, momentum width distributions, and velocities of the projectile-like fragments in the⁴⁰Ar on⁶⁸Zn reaction have been measured at 27.6 MeV/nucleon incident energy. The results show the existence of a fragmentation process well described in the framework of the high energy fragmentation model. However, important contributions from direct nucleon transfer and damped collisions are present.