Semisynthesis of new D-seco-C-nor-taxane derivatives containing a polyfunctionalized furanosyl or cyclopentenyl or cyclopentyl C-ring

The synthesis of new D-seco-C-nor-taxane derivatives in which the D-ring has been deleted and the C-ring has been transformed into a new pentatomic ring, i.e., the polyfunctionalized tetrahydrofuranosyl and cyclopentenyl or cyclopentyl ring, was performed starting from baccatin III derivatives. The synthetic strategy adopted took advantage of the oxetane ring opening and disconnection of the C4-C5 bond, followed by an intramolecular condensation. The formation of furanosyl or cyclopentyl rings is strictly dependent on the presence of unprotected or protected oxygen at C-7 in the starting material. The reactions proceeded with good diastereoselectivity with control of the stereochemistry of one or two stereocenters.     

Anti-Ramsey Numbers of Graphs with Small Connected Components

The anti-Ramsey number, AR(n, G), for a graph G and an integer \(n\ge |V(G)|\), is defined to be the minimal integer r such that in any edge-colouring of \(K_n\) by at least r colours there is a multicoloured copy of G, namely, a copy of G that each of its edges has a distinct colour. In this paper we determine, for large enough \(n,\, AR(n,L\cup tP_2)\) and \(AR(n,L\cup kP_3)\) for any large enough t and k, and a graph L satisfying some conditions. Consequently, we determine AR(n, G), for large enough n, where G is \(P_3\cup tP_2\) for any \(t\ge 3,\, P_4\cup tP_2\) and \(C_3\cup tP_2\) for any \(t\ge 2,\, kP_3\) for any \(k\ge 3,\, tP_2\cup kP_3\) for any \(t\ge 1,\, k\ge 2\), and \(P_{t+1}\cup kP_3\) for any \(t\ge 3,\, k\ge 1\). Furthermore, we obtain upper and lower bounds for AR(n, G), for large enough n, where G is \(P_{k+1}\cup tP_2\) and \(C_k\cup tP_2\) for any \(k\ge 4,\, t\ge 1\).     

Structural studies of supported tin catalysts

Tin oxide was supported on aluminium oxide, titanium oxide, magnesium oxide and silicon oxide, and the resulting interactions between the components in the prepared samples and after reduction were characterized by Mössbauer spectroscopy. It was observed that in the oxide state, tin is present as SnO₂ on alumina, magnesia and silica, but on titania tin occupies Ti sites in the structure. After hydrogen treatment at high temperatures, tin is reduced from Sn(4) to Sn(2) on alumina and titania; it is reduced from Sn(4) to Sn(0) on silica, and is practically not reduced on magnesia. These results reveal the degree of interaction between tin and the different supports studied.     

Synthesis of Amphiphilic Fullerene Derivatives and Their Incorporation in Langmuir and Langmuir‐Blodgett Films

Various amphiphilic fullerene derivatives were prepared by functionalization of [5,6]fullerene‐C₆₀‐I_h (C₆₀) with malonate or bis‐malonate derivatives obtained by esterification of the malonic acid mono‐esters 5 – 7 . Cyclopropafullerene 10 was obtained by protection of the carboxylic acid function of 6 as a tert‐butyl ester, followed by Bingel addition to C₆₀ and a deprotection step (Scheme 2). The preparation of 10 was also attempted directly from the malonic acid mono‐ester 6 under Bingel conditions. Surprisingly, the corresponding 3′‐iodo‐3′H‐cyclopropa[1,9][5,6]fullerene‐C₆₀‐I_h‐3′‐carboxylate 11 was formed instead of 10 (Scheme 3). The general character of this new reaction was confirmed by the preparation of 15 and 16 from the malonic acid mono‐esters 13 and 14 , respectively (Scheme 4). All the other amphiphilic fullerene derivatives were prepared by taking advantage of the versatile regioselective reaction developed by Diederich and co‐workers which led to macrocyclic bis‐adducts of C₆₀ by a cyclization reaction at the C‐sphere with bis‐malonate derivatives in a double Bingel cyclopropanation. The bis‐adducts 37 – 39 with a carboxylic acid polar head group and four pendant long alkyl chains of different length were prepared from diol 22 and acids 5 – 7 , respectively (Scheme 9). In addition, the amphiphilic fullerene derivatives 45, 46, 49, 54 , and 55 bearing different polar head groups and compound 19 with no polar head group were synthesized (Schemes 11–13, 15, and 5, resp.). The ability of all these compounds to form Langmuir monolayers at the air‐water interface was investigated in a systematic study. The films at the water surface were characterized by their surface pressure vs. molecular area isotherms, compression and expansion cycles, and Brewster‐angle microscopy. The spreading behavior of compound 10 was not good, the two long alkyl chains in 10 being insufficient to prevent aggregation resulting from the strong fullerene‐fullerene interactions. While no films could be obtained from compound 19 with no polar head group, all the corresponding amphiphilic fullerene bis‐adducts showed good spreading characteristics and reversible behavior upon successive compression/expansion cycles. The encapsulation of the fullerene in a cyclic addend surrounded by four long alkyl chains is, therefore, an efficient strategy to prevent the irreversible aggregation resulting from strong fullerene‐fullerene interactions usually observed for amphiphilic C₆₀ derivatives at the air‐water interface. The balance of hydrophobicity to hydrophilicity was modulated by changing the length of the surrounding alkyl chains or the nature of the polar head group. The best results in terms of film formation and stability were obtained with the compounds having the largest polar head group, i.e. 45 and 46 , and dodecyl chains. Finally, the Langmuir films obtained from the amphiphilic fullerene bis‐adducts were transferred onto solid substrates, yielding high‐quality Langmuir‐Blodgett films.     

Cycloaddition reactions of 1,3-diazabuta-1,3-dienes with alkynyl ketenes

The cycloaddition reactions of ‘all-carbon’ 1,3-diazabuta-1,3-dienes with a few conjugated and unconjugated alkynyl ketenes are described. The reactions provide some interesting azetidinones and dihydropyrimidinones bearing an alkynyl moiety. The regiochemistry of cycloadduct is related with the degree of conjugation of the alkynyl ketene. Moreover, two alternative approaches to ‘all-carbon’ 1,3-diazabuta-1,3-dienes are reported.     

A Hybrid DNA Aptamer–Dendrimer Nanomaterial for Targeted Cell Labeling

Antibodies are natural nanomaterials and have been widely used for targeted cell labeling. However, the applications of antibodies are often limited by their large size and instability. The purpose of this study is to develop a new type of multifunctional nanomaterial that is comprised of a nucleic acid aptamer and a dendrimer, both of which are stable. This nanomaterial is ≈8 nm in size. Moreover, it could not only carry multiple signal molecules, but also bind to target cancer cells with high affinity and specificity. This sub‐10 nm multifunctional nanomaterial is expected to be useful in basic biomedical research and clinical medicine.

     

CXMS and XRD analyses of heat treated A533B stainless steel

Heat induced surface changes on A533B stainless steel were followed by XRD and CXMS techniques. Whereas the XRD patterns of the studied A533B samples were characteristic of α-Fe phase only, the surface Mössbauer spectrum showed a broad sextet, being fitted with two magnetic patterns whose hyperfine magnetic fields were 33 and 31 T associated with a pure and perturbed α-Fe phase, respectively and a broad singlet with an isomer shift δ _A533B = ?0.115(4) mms $^{-1}/\alpha $ -Fe, characteristic of the γ-Fe phase. This singlet, probably, arising from the samples’ surface only was further analyzed by using a singlet and a quadrupole doublet. From hyperfine distribution and discrete value calculations of their corresponding hyperfine parameters, the quadrupole interaction was the most affected by thermal treatments ranging from 300° to 700 °C showing a slight decrease at 600 °C. The average values of the hyperfine parameters were δ ₁ = ? 0.110(6) mms $^{-1}/\alpha $ -Fe for the singlet, and δ ₂ = ?0.081 (6) mms $^{-1}/\alpha $ -Fe and Δ₂ = 0.143(7) mm/s) for the quadrupole doublet, respectively. In spite of the temperature dependence of the quadrupole splitting on the doublet, which was higher than that of the isomer shifts of both patterns, only a single defect type was suggested, being associated with monovacancias near the ⁵⁷Fe sites.     

Expression and Structure/Function Relationships of Human Defensin 5

The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3–5 kDa), among them defensins. In humans, defensins are the first line of defense against pathogens and their expression has been implicated in several diseases. The antibacterial activity of defensins is generally ascribed to their overall positive charge, which enables them to disrupt bacterial membrane integrity and function, but their active surface has not been fully elucidated. To perform structural and functional assays, an efficient, high-yield, easy-to-use expression and purification system must be established. Up to now, most efforts to obtain larger quantities of active recombinant defensins have been only moderately successful. Herein, we report the establishment of an efficient, high-yield expression and purification system for human defensin 5 (HD-5). Using site-directed mutagenesis, we pinpoint several arginine residues and Y27 as important for HD-5 antibacterial activity. Our expression and purification system can be harnessed for structure/activity relationship studies of defensins in particular and small polypeptides in general.     

Cold-field switching in PVDF-TrFE ferroelectric polymer nanomesas

Polarization reversal in ferroelectric nanomesas of polyvinylidene fluoride with trifluoroethylene has been probed by ultrahigh vacuum piezoresponse force microscopy in a wide temperature range from 89 to 326 K. In dramatic contrast to the macroscopic data, the piezoresponse force microscopy local switching was nonthermally activated and, at the same time, occurring at electric fields significantly lower than the intrinsic switching threshold. A "cold-field" defect-mediated extrinsic switching is shown to be an adequate scenario describing this peculiar switching behavior. The extrinsic character of the observed polarization reversal suggests that there is no fundamental bar for lowering the coercive field in ferroelectric polymer nanostructures, which is of importance for their applications in functional electronics.     

Capillary size exclusion chromatography with picogram sensitivity for analysis of monoclonal antibodies purified from harvested cell culture fluid

Size exclusion chromatography (SEC) is widely used in the characterization and quality control of therapeutic proteins to detect aggregates. Aggregation is a carefully monitored quality attribute from the earliest stages of clinical development owing to the possibility of eliciting an immunogenic response in the patient. During early stage molecule assessment for cell culture production, small-scale screening experiments are performed to permit rapid turn-around of results so as to not delay timelines. We report the development of a capillary SEC methodology for preliminary molecule assessment to support the evaluation of therapeutic candidates at an early stage of development. By making several key modifications to a commercially available liquid chromatography system, we demonstrate a platform process to perform capillary SEC with excellent precision, picogram sensitivity and good ruggedness. The limit of quantitation was determined to be approximately 15 pg; picogram sensitivity for SEC analysis of monoclonal antibodies had not been achieved prior to this work. In addition, we have developed a method to capture low levels of antibody (1 μg/mL) from harvested cell culture fluid (HCCF) for capillary SEC analysis. Up to 40% recovery efficiency was achieved using this micro-recovery method on 3 mL HCCF samples. Using early stage cell culture transient transfection samples, which typically have much lower titers than stable cell line samples, we demonstrate a consistent method for analyzing aggregates in low protein concentration HCCF samples for molecule assessment and early stage candidate screening.