Organic-inorganic telechelic molecules: solution properties from simulations

We report molecular dynamics simulations for telechelic molecules composed of two polyhedral oligomeric silsesquioxane (POSS) cages connected by one hydrocarbon backbone dissolved in liquid normal hexane. Silsesquioxanes are novel hybrid organic-inorganic molecules that are useful as building blocks for the synthesis of nanostructured materials. By including POSS molecules within a polymeric material it is possible to modify mechanical properties such as resistance to heat and glass transition temperatures. Unfortunately, the molecular mechanisms responsible for these enhancements are at present not completely understood. In an effort to elucidate the molecular phenomena responsible for these effects, we have studied the conformation of telechelic POSS molecules in solution, as well as their self-diffusion coefficients, as a function of the length of the hydrocarbon backbone. We focus on molecules in which the radius of gyration of the alkane backbone is comparable to the size of the silsesquioxane cages. Our results indicate that the backbone has a significant influence on both the equilibrium and the transport properties of dissolved telechelic hybrid molecules. These observations are useful for developing strategies to direct the self-assembly of nanostructured materials.     

Separation of fluorinated amino acids and oligopeptides from their non-fluorinated counterparts using high-performance liquid chromatography

Chromatographic conditions for the separation of fluorinated amino acids and oligopeptides from their non-fluorinated counterparts were explored. The separation of six pairs of analytes, including both aromatic and aliphatic fluorocarbons, was investigated at various temperatures using both hydrocarbon and fluorocarbon columns and eluents. Our results show that when hydrocarbon eluents are used, fluorocarbon column provides better separation of fluorinated amino acids or oligopeptides from their non-fluorinated counterparts; when fluorocarbon eluents are used, hydrocarbon column provides better separation of fluorinated amino acids or oligopeptides from their non-fluorinated counterparts. These chromatographic behaviors reflect the fluorophilicity possessed by fluorinated amino acids and oligopeptides.     

Bile Acid Conjugates with Anticancer Activity: Most Recent Research

The advantages of a treatment modality that combines two or more therapeutic agents in cancer therapy encourages the study of hybrid functional compounds for pharmacological applications. In light of this, we reviewed recent works on hybrid molecules based on bile acids. Due to their biological properties, as well as their different chemical/biochemical reactive moieties, bile acids can be considered very interesting starting molecules for conjugation with natural or synthetic bioactive molecules.     

Inclusion of poly-aromatic hydrocarbon (PAH) molecules in a functionalized layered double hydroxide

The internal surface of an Mg-Al layered double hydroxide has been functionalized by anchoring carboxy-methyl derivatized β-cyclodextrin cavities to the gallery walls. Neutral polyaromatic hydrocarbon (PAH) molecules have been included within the functionalized solid by driving the hydrophobic aromatic molecules from a polar solvent into the less polar interior of the anchored cyclodextrin cavities by a partitioning process. The optical (absorption and emission) properties of the PAH molecules included within the functionalized Mg-Al layered double hydroxide solid are similar to that of dilute solutions of the PAH in non-polar solvents. The unique feature of these hybrid materials is that they are thermally stable over a wide temperature range with their emission properties practically unaltered. Dedicated to Prof J Gopalakrishnan on his 62nd birthday.     

Molecular mechanisms of ion-specific effects on proteins

The specific binding sites of Hofmeister ions with an uncharged 600-residue elastin-like polypeptide, (VPGVG)(120), were elucidated using a combination of NMR and thermodynamic measurements along with molecular dynamics simulations. It was found that the large soft anions such as SCN(-) and I(-) interact with the polypeptide backbone via a hybrid binding site that consists of the amide nitrogen and the adjacent α-carbon. The hydrocarbon groups at these sites bear a slight positive charge, which enhances anion binding without disrupting specific hydrogen bonds to water molecules. The hydrophobic side chains do not contribute significantly to anion binding or the corresponding salting-in behavior of the biopolymer. Cl(-) binds far more weakly to the amide nitrogen/α-carbon binding site, while SO(4)(2-) is repelled from both the backbone and hydrophobic side chains of the polypeptide. The Na(+) counterions are also repelled from the polypeptide. The identification of these molecular-level binding sites provides new insights into the mechanism of peptide-anion interactions.     

Hybrid QM/MM simulation of the hydration phenomena of dipalmitoylphosphatidylcholine headgroup

The polar headgroup of dipalmitoylphosphatidylcholine (DPPC) molecule both in gas phase and aqueous solution is investigated by the hybrid quantum mechanical/molecular mechanical (QM/MM) method, in which the polar head of DPPC molecule and the bound water molecules are treated with density functional theory (DFT), while the apolar hydrocarbon chain of DPPC molecule is treated with MM method. It is demonstrated that the hybrid QM/MM method is both accurate and efficient to describe the conformations of DPPC headgroup. Folded structures of headgroup are found in gas phase calculations. In this work, both monohydration and polyhydration phenomena are investigated. In monohydration, different water association sites are studied. Both the hydration energy and the quantum properties of DPPC and water molecules are calculated at the DFT level of theory after geometry optimization. The binding force of monohydration is estimated by using the scan method. In polyhydration, more extended conformations are found and hydration energies in different polyhydration styles are estimated.     

Early events in radiation chemistry and in photoionization

Real-time studies of aliphatic and aromatic hydrocarbons by pulse radiolysis and laser photoionization reveal the chemistry of the ionic species in the condensed phase. The occurrence of radical cation reactions with solvent molecules provides the core mechanism capable of explaining a wide range of observations in photoionization and radiation chemistry. The study of products and transients in photoionization of aromatic solutes in hydrocarbon and alcohol solvents illustrates several details of this “high-energy” chemistry. A reaction pathway involving ion-molecule reaction of excited ions is indicated for a series of polycyclic aromatic hydrocarbons photoionized using intense excimer laser (248 and 308 nm) pulses in hydrocarbon and alcohol solutions. We have found that condensed-phase ion-molecule reactions in radiolysis are ubiquitous and we speculate on their overall role in hydrocarbon radiolysis.     

Design,Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.     

Deaggregation behavior of the phenol gemini derivatives

The phenol gemini compounds were synthesized by rebuilding the substituents and lateral chain on the phenyl ring. Two parts of the molecules were connected by a spacer of hydrocarbon chain via ester groups. The deaggregation behaviors of target molecules were investigated by studying coaggregation behaviors, evaluating the deaggregating abilities in terms of fluorescence measurements, the measurements of their aggregation number and the effects on restraining the cell adhesion. In present cases, all of these experiments give the same results; that is, in these molecules, the longer branched methyl hydrocarbon chain and the combination of methoxy with hydroxyl groups on the phenyl ring possess the higher deaggregating abilities in the studied situation. The molecules with two hydrocarbon chains, i.e., the phenol gemini compounds, are more effective to deaggregate the aggregated probes than the molecules with one hydrocarbon chain. To find an effective deaggregator might be helpful to design the medicine for the cure of arteriosclerosis.     

Exploiting enzymatic regioselectivity: a facile methodology for the synthesis of polyhydroxylated hybrid compounds

Polyhydroxylated hybrid molecules have been synthesized using a protocol based on the regioselective acylation of the target compounds with activated dicarboxylic acids catalyzed by Novozym-435. The procedure implies that the mixed ester derivatives prepared and isolated from the first esterification step act as acylating agents in the second esterification step.     

Synthesis of conformationally constrained C-glycosyl alpha- and beta-amino acids and sugar-carbamino sugar hybrids via Diels-Alder reaction

[structure: see text] Sugar-derived dienes undergo Diels-Alder reactions with methyl alpha-nitro acrylate and ethyl beta-nitro acrylate to form the corresponding cycloadducts which have been converted into conformationally constrained C-glycosyl alpha- and beta-amino acids. Further, these beta-amino acids are converted into sugar-carbamino sugar hybrid molecules.     

Modified Nucleosides,Nucleotides and Nucleic Acids via Click Azide-Alkyne Cycloaddition for Pharmacological Applications

The click azide = alkyne 1,3-dipolar cycloaddition (click chemistry) has become the approach of choice for bioconjugations in medicinal chemistry, providing facile reaction conditions amenable to both small and biological molecules. Many nucleoside analogs are known for their marked impact in cancer therapy and for the treatment of virus diseases and new targeted oligonucleotides have been developed for different purposes. The click chemistry allowing the tolerated union between units with a wide diversity of functional groups represents a robust means of designing new hybrid compounds with an extraordinary diversity of applications. This review provides an overview of the most recent works related to the use of click chemistry methodology in the field of nucleosides, nucleotides and nucleic acids for pharmacological applications.     

ON THE PHENOMENOLOGICAL THERMODYNAMICS OF HYDROPHOBIC BONDING

This paper is a review of the points of view of Frank and Evans, Shinoda and the author regarding the hydrophobic hydration of hydrocarbon molecules, with the emphasis on the contribution of the author. It is demonstrated that the enthalpic free energy change, due to the interactions between the hydrocarbon molecules and water, is compensated by the entropic free energy change, due to the ordering caused by the hydrocarbon molecules in the neighboring water molecules. Further, it is shown that the free energy change due to the iceberg formation is negative. Some simplifying assumptions make it possible to conclude that the absolute value of the free energy for iceberg formation can be as large as 1/3 of the free energy change associated with the formation of a cavity. The thermodynamic approach employed can also explain the existence of a minimum in the temperature dependence of the hydrocarbon solubility in water.     

FT-Raman studies of langmuir-blodgett monolayer components containing absorbing chromophores

Structural studies of Langmuir-Blodgett monolayers and multilayers have revealed that both the hydrophilic and the hydrophobic parts of an amphiphilic molecule can influence the exent of 2-dimensional packing which occurs within a film. In particular, dye chromophores to which are appended long hydrocarbon tails will usually form films dominated by the interaction of the chromophores unless a small amount of hydrocarbon liquid is added. In this case the packing will be dominated by the intermolecular interaction of the hydrocarbon tails. FT-Raman studies of these amphiphilic molecules provides information about both parts of the molecule without resonance enhancement since the laser wavelength used for excitation is far removed from any absorption maxima of the dye chromophore. Specific examples of thiocyanine and merocyanine dyes will be discussed.     

Phospholipid monolayers

Summary The action of polymerized silicic acid on lecithin and cephalin monolayers brings about changes in its physical state, molecular area, and pressure of collapse. These changes are more notable in the case of lecithins, varying not only with the substrate pH, but also with the length of the hydrocarbon chains of the fatty acids that esterify glycerol in the molecules of these substances. The different actions observed between silicic acid and the lecithin and cephalin monolayers are explained with the help of different models.With 11 figures     

Gauge-origin-independent magnetizabilities of solvated molecules using the polarizable continuum model

We present an implementation of the polarizable continuum model in its integral equation formulation for the calculation of the magnetizabilities of solvated molecules. The gauge-origin independence of the calculated magnetizabilities and the fast basis set convergence are ensured through the use of London atomic orbitals. Our implementation can use Hartree-Fock and multiconfigurational self-consistent-field (MCSCF) wave functions as well as density-functional theory including hybrid functionals such as B3LYP. We present the results of dielectric continuum effects on water and pyridine using MCSCF wave functions, as well as dielectric medium effects on the magnetizability of the aromatic amino acids as a model for how a surrounding protein environment affects the magnetizability of these molecules. It is demonstrated that the dielectric medium effects on the magnetizability anisotropies of the aromatic amino acids may be substantial, being as large as 25% in the case of tyrosine.     

含有十核羧酸一水杂化簇合物的二维铜配位聚合物的构筑

以新生的氢氧化铜、2,2’-二苯基二羧酸（H2bpda）以及柔性配体l,3二（4．吡啶）丙烷（bpp）N原料,超声反应条件下,在甲醇．水混合溶剂中合成了1个新型配合物,{[cu2（bpp）2（H20）2（bpda）2]．6H2O}。（1）,并对该配合物进行了元素分析、红外光谱分析、热重分析、脱水／重新吸水分析以及晶体结构研究X射线单晶结构分析表明,配合物1中含有一种由类似椅式构象的六核水簇及两个水分子所组成的八核水簇．该八核水簇结构类似环脂烃（1r,4r）二甲基-环己烷,显示出水分子簇与有机分子结构上的相似性．有趣的是,该八核水簇与周围羧酸根中的氧原子通过氢键作用形成了类似于（H2O）10纯水簇的十核羧酸一水杂化簇合物．此外,该配合物具有可逆的脱水／重新吸水性能．     

Applications of electrospray ionization mass spectrometry to neutral organic molecules including fullerenes

The use of electrospray ionization mass spectrometry (ESI/MS) for the detection of neutral organic molecules becomes possible by their derivation with specific ESI/MS tagging reagents that have either proton or metal ion binding sites. We used the neutral crown ether group in several reagents to attach a metal binding site to substrate molecules. Application of this method to steroids, amino acids, vitamin D, fatty acids, and fullerenes is described. Besides characterization, tagged molecules can be used for studying organic reactions by ESI/MS. This work demonstrates that ESI/MS provides a unique window on fullerene solution chemistry. ESI/MS is not only an excellent tool for the analysis of biopolymers but is also useful for studying the organic chemistry of small neutral molecules.