Two isomorphous benzene­sulfon­amide crystal structures determined by intermolecular C—H⃛O,C—H⃛π and C—H⃛Cl interactions

The title compounds, N‐[5‐(4‐chloro­phenyl)­furan‐2‐yl­methyl]‐4‐methyl‐N‐(prop‐2‐ynyl)­benzene­sulfon­amide, (Ia), and N‐[5‐(2‐chloro­phenyl)­furan‐2‐yl­methyl]‐4‐methyl‐N‐(prop‐2‐ynyl)­benzene­sulfon­amide, (Ib), both C₂₁H₁₈ClNO₃S, have isomorphous crystal structures. The crystal packing is mainly determined by intermolecular C—H?O and C—H?π interactions. These interactions are very similar in (Ia) and (Ib). Additional intermolecular C—H?Cl interactions appear less important and are different in (Ia) and (Ib). The different positions of the Cl atoms result in small variations of the crystal packing of the two compounds.     

Molecular hydrophobic attraction and ion-specific effects studied by molecular dynamics

Much is written about "hydrophobic forces" that act between solvated molecules and nonpolar interfaces, but it is not always clear what causes these forces and whether they should be labeled as hydrophobic. Hydrophobic effects roughly fall in two classes, those that are influenced by the addition of salt and those that are not. Bubble adsorption and cavitation effects plague experiments and simulations of interacting extended hydrophobic surfaces and lead to a strong, almost irreversible attraction that has little or no dependence on salt type and concentration. In this paper, we are concerned with hydrophobic interactions between single molecules and extended surfaces and try to elucidate the relation to electrostatic and ion-specific effects. For these nanoscopic hydrophobic forces, bubbles and cavitation effects play only a minor role and even if present cause no equilibration problems. In specific, we study the forced desorption of peptides from nonpolar interfaces by means of molecular dynamics simulations and determine the adsorption potential of mean force. The simulation results for peptides compare well with corresponding AFM experiments. An analysis of the various contributions to the total peptide-surface interactions shows that structural effects of water as well as van der Waals interactions between surface and peptide are important. Hofmeister ion effects are studied by separately determining the effective interaction of various ions with hydrophobic surfaces. An extension of the Poisson-Boltzmann equation that includes the ion-specific potential of mean force yields surface potentials, interfacial tensions, and effective interactions between hydrophobic surfaces. There, we also analyze the energetic contributions to the potential of mean force and find that the most important factor determining ion-specific adsorption at hydrophobic surfaces can best be described as surface-modified ion hydration.     

Comparative analysis of CE‐SSCP to standard RFLP‐CE‐FLA method in quantification of known viral variants within an RNA virus quasispecies

RNA viruses display the highest replication error rate in our biosphere, leading to highly diverse viral populations termed quasispecies. The gold standard method for detection and quantification of variants in a quasispecies is cloning and sequencing, but it is expensive, laborious and time consuming. Therefore, other mutation detection approaches, including SSCP, are often used. In this study, we demonstrate development and the usage of a CE‐SSCP method for quantification of two nearly identical viral variants in heterogenic population of a mumps virus strain and its comparison to RFLP‐CE‐fragment length analysis (RFLP‐CE‐FLA). Analyzed PCR fragments were of the same size (245 bp) with one difference in their nucleotide sequence. The limit of detection of both methods was at 5% of the minor variant. When PCR amplicons of the two variants were pooled, methods' results were very similar. On the contrary, the quantification results of samples in which variants were mixed prior to PCR showed substantial difference between the two methods. Our results indicate that although both methods can be used for detection and monitoring of a specific mutation within a viral population, caution should be taken when quantitative analysis of complex samples is based solely on results of one method.     

One tool to bring them all: Au-catalyzed synthesis of B,O- and B,N-doped PAHs from boronic and borinic acids

The isoelectronic replacement of C C bonds with ⁻B N⁺ bonds in polycyclic aromatic hydrocarbons (PAHs) is a widely used tool to prepare novel optoelectronic materials. Far less well explored are corresponding B,O-doped PAHs, although they have a similarly high application potential. We herein report on the modular synthesis of B,N- and B,O-doped PAHs through the [Au(PPh₃)NTf₂]-catalyzed 6-endo-dig cyclization of BN–H and BO–H bonds across suitably positioned C C bonds in the key step. Readily available, easy-to-handle o-alkynylaryl boronic and borinic acids serve as starting materials, which are either cyclized directly or first converted into the corresponding aminoboranes and then cyclized. The reaction even tolerates bulky mesityl substituents on boron, which later kinetically protect the formed B,N/O-PAHs from hydrolysis or oxidation. Our approach is also applicable for the synthesis of rare doubly B,N/O-doped PAHs. Specifically, we prepared 1,2-B,E-naphthalenes and -anthracenes, 1,5-B₂-2,6-E₂-anthracenes (E = N, O) as well as B,O₂-containing and unprecedented B,N,O-containing phenalenyls. Selected examples of these compounds have been structurally characterized by X-ray crystallography; their optoelectronic properties have been studied by cyclic voltammetry, electron spectroscopy, and quantum-chemical calculations. Using a new unsubstituted (B,O)₂-perylene as the substrate for late-stage functionalization, we finally show that the introduction of two pinacolatoboryl (Bpin) substituents is possible in high yield and with perfect regioselectivity via an Ir-catalyzed C–H borylation approach.

Singly and doubly B,E-doped PAHs were synthesized using a protocol that starts from easy-to-handle boronic and borinic acids and offers the possibility to choose between the preparation of B,O- and B,N-PAHs in the final reaction step.     

Fully Synthetic Self‐Adjuvanting Thioether‐Conjugated Glycopeptide?Lipopeptide Antitumor Vaccines for the Induction of Complement‐Dependent Cytotoxicity against Tumor Cells

Glycopeptides of tumor‐associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune‐response‐stimulating T‐cell epitopes and the Pam₃Cys lipopeptide to induce strong immune responses in mice. A new thioether‐ligation method for the synthesis of two‐ and three‐component vaccines that contain MUC1 glycopeptides as the B‐cell epitopes, a T‐cell epitope peptide, and the Pam₃CSK₄ lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund′s adjuvant or in aqueous PBS buffer. The three‐component vaccines that contained the Tetanus Toxoid P2 T‐cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement‐dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.     

Synthesis of intrinsically flame‐retardant copolyamides and their employment in PA6‐fibers

Flame‐retarded polyamide 6.6 (FR‐PA6.6) was prepared by the cocondensation of hexamethylene diammonium adipate (AH‐salt) with the corresponding salts of hexamethylene diamine and two different organophosphorus compounds, namely, 3‐hydroxyphenylphosphinylpropanoic acid (3‐HPP, 1) and 9,10‐dihydro‐10‐[2,3‐di (hydroxycarbonylpropyl]‐10‐phosphaphenanthrene‐10‐oxide (DDP, 2). The incorporation of the phosphorus comonomers and the thermal and physical properties of the resulting copolyamides have been studied. The phosphorus‐modified FR‐PA6.6 possesses high relative viscosities of 2.0 to 2.4, good thermal stability, and was used for the production of polyamide blends by merging FR‐PA6.6 with commercial PA6. This offered access to flame‐retarded PA6 multifilaments, which possess tensile strengths up to 0.7 GPa and elastic moduli up to 6.2 GPa. Knitted fabrics of FR‐PA6 exhibit high limiting oxygen index (LOI) values between 36 and 38 and executed burning tests demonstrate that the incorporation of phosphorus‐based comonomers improve flame retardancy significantly. The approach presented here offers a straightforward access to effective flame retardancy in nylon 6.     

Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines

In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the allylic HYCRON or the fluoride-sensitive PTMSEL anchor, the antigenic glycopeptide structures were constructed on the solid phase utilizing pre-assembled glycosyl amino acid building blocks prepared in solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced applying a construct composed of a sialyl-T(N) MUC1-glycopeptide conjugated with a tetanus toxin T cell peptide epitope.