DNA Interstrand Cross‐Links of an Antitumor Trinuclear Platinum(II) Complex: Thermodynamic Analysis and Chemical Probing

The trinuclear platinum compound [{trans‐PtCl(NH₃)₂}₂(μ‐trans‐Pt(NH₃)₂{NH₂(CH₂)₆NH₂}₂)]⁴⁺ (BBR3464) belongs to the polynuclear class of platinum‐based anticancer agents. These agents form in DNA long‐range (Pt,Pt) interstrand cross‐links, whose role in the antitumor effects of BBR3464 predominates. Our results show for the first time that the interstrand cross‐links formed by BBR3464 between two guanine bases in opposite strands separated by two base pairs (1,4‐interstrand cross‐links) exist as two distinct conformers, which are not interconvertible, not only if these cross‐links are formed in the 5′‐5′, but also in the less‐usual 3′‐3’ direction. Analysis of the conformers by differential scanning calorimetry, chemical probes of DNA conformation, and minor groove binder Hoechst 33258 demonstrate that each of the four conformers affects DNA in a distinctly different way and adopts a different conformation. The results also support the thesis that the molecule of antitumor BBR3464 when forming DNA interstrand cross‐links may adopt different global structures, including different configurations of the linker chain of BBR3464 in the minor groove of DNA. Our findings suggest that the multiple DNA interstrand cross‐links available to BBR3464 may all contribute substantially to its cytotoxicity.     

Reduced Kinetic Schemes of Complex Reaction Systems: Fossil and Biomass‐Derived Transportation Fuels

The kinetic modeling of the pyrolysis and combustion of liquid transportation fuels is a very complex task for two different reasons: the challenging characterization of the complex mixture of several hydrocarbon isomers and the complexity of the oxidation mechanisms of large hydrocarbon and oxygenated molecules. While surrogate mixtures of reference components allow to tackle the first difficulty, the complex behavior of the oxidation mechanisms is mostly overcome by reducing the total number of involved species by adopting a lumping approach. After a first investigation of the different liquid fuels (gasoline, kerosene, and diesel fuels), a short discussion on the lumping techniques allows to highlight the advantages of this approach. The lumped POLIMI pyrolysis and oxidation mechanism of hydrocarbon and oxygenated fuels is then used for generating several skeletal mechanisms for typical surrogate mixtures, moving from pure n‐heptane up to heavy diesel fuels. These skeletal models are simply reduced with a reaction flux analysis, and they involve between 100 and 200 species. While these sizes already allow detailed computational fluid dynamics (CFD) calculations in internal combustion engines, further reduction phases are necessary when the interest is toward more complex CFD computations. To maintain the standard structure of the skeletal mechanisms, successive reduction phases are not considered. Moreover, new regulations pushed toward a greater use of renewable fuels. For these reasons, the skeletal models are also extended to biogasolines including methanol, ethanol, and n‐butanol. Similarly, skeletal models of diesel and biodiesel fuels, including methyl esters, are also provided. Several comparisons with experimental data and complete validations in the operating range of internal combustion engines are also reported. The whole set of comparisons with experimental data obtained in a wide range of conditions not only validate the reduced models of specific transportation fuels but also the complete kinetic scheme POLIMI_1404.     

钴(II)-联吡啶-α-氨基酸的热力学和动力学研究

关于联吡啶为第一配体的二元、三元配合物的热力学和动力学性质的研究,以铜（Ⅱ）作为中心离子最为多见,而以钴（Ⅱ）作为中心离子的报导较少．实验表明,过渡金属钻（Ⅱ）能与大多数的生物配体、大π共轭体系形成相当稳定的二元、三元配合物,是生物功能模拟的一个具有应用价值的中心离子·钴（Ⅱ）卟啉可以代替铁（Ⅱ）卟啉,模拟血红蛋白、肌红蛋白[1],在生物体内起到输送氧的作用．为了充分了解钴（Ⅱ）与生物配体的配伍能力、配位方式以及其配位过程的动态行为,为推动钴（Ⅱ）配合物及其生物功能的模拟研究,本文分别采用PH电位法…     

Multi‐Morphological Complex Aggregates Formed from Amphiphilic Poly(ethylene oxide)‐block‐Polydimethylsiloxane‐block‐Poly(ethylene oxide) Triblock Copolymers

Summary: Amphiphilic triblock copolymers (PEO_x‐b‐PDMS_y‐b‐PEO_x) with different block lengths were synthesized and multi‐morphological complex crew‐cut, star‐like, and short‐chain aggregates were prepared by self‐assembly of the given copolymers. The morphologies and dimensions of the aggregates can be well controlled by variation of the preparation conditions. TEM, SEM, FFR‐TEM, and LLS studies show the resulting morphologies range from LCMs, unilamellar or multilayer vesicles, LCVs, porous spheres to nanorods.

TEM images of the vesicles formed from PEO‐b‐PDMS‐b‐PEO.     

An N‐Heterocyclic Silylene‐Stabilized Digermanium(0) Complex

The synthesis of an N‐heterocyclic silylene‐stabilized digermanium(0) complex is described. The reaction of the amidinate‐stabilized silicon(II) amide [LSiN(SiMe₃)₂] ( 1 ; L=PhC(NtBu)₂) with GeCl₂?dioxane in toluene afforded the Si^II–Ge^II adduct [L{(Me₃Si)₂N}Si→GeCl₂] ( 2 ). Reaction of the adduct with two equivalents of KC₈ in toluene at room temperature afforded the N‐heterocyclic carbene silylene‐stabilized digermanium(0) complex [L{(Me₃Si)₂N}Si→ Ge?Ge←Si{N(SiMe₃)₂}L] ( 3 ). X‐ray crystallography and theoretical studies show conclusively that the N‐heterocyclic silylenes stabilize the singlet digermanium(0) moiety by a weak synergic donor–acceptor interaction.     

A Chemical Kinetic Mechanism for 2‐Bromo‐3,3,3‐trifluoropropene (2‐BTP) Flame Inhibition

In this work, we report a detailed chemical kinetic mechanism to describe the flame inhibition chemistry of the fire‐suppressant 2‐bromo‐3,3,3‐trifluoropropene (2‐BTP), under consideration as a replacement for CF₃Br. Under some conditions, the effectiveness of 2‐BTP is similar to that of CF₃Br; however, like other potential halon replacements, it failed an U.S. Federal Aviation Authority (FAA) qualifying test for its use in cargo bays. Large overpressures are observed in that test and indicate an exothermic reaction of the agent under those conditions. The kinetic model reported herein lays the groundwork to understand the seemingly conflicting behavior on a fundamental basis. The present mechanism and parameters are based on an extensive literature review supplemented with new quantum chemical calculations. The first part of the present article documents the information considered and provides traceability with respect to the reaction set, species thermochemistry, and kinetic parameters. In additional work, presented more fully elsewhere, we have combined the 2‐BTP chemical kinetic mechanism developed here with several other submodels from the literature and then used the combined mechanism to simulate premixed flames over a range of fuel/air stoichiometries and agent loadings. Overall, the modeling results qualitatively predicted observations found in cup‐burner tests and FAA Aerosol Can Tests, including the extinguishing concentrations required and the lean‐to‐rich dependence of mixtures. With these data in hand, in a second phase of the present work, we perform a reaction path analysis of major species under several modeled conditions. This analysis leads to a qualitative understanding of the ability of 2‐BTP to act as both an inhibitor and a fuel, depending on the conditions and suggests areas of the kinetic model that should be further investigated and refined.     

Multi‐Channel Surface Acoustic Wave Sensors Based on Principal Component Analysis (PCA) and Linear Discriminate Analysis (LDA) for Organic Vapors

A multi‐channel surface acoustic wave (SAW) detection system which is employed to detect various organic molecules in a static system was prepared using 315 MHz one‐port quartz resonators and a home‐made computer interface for signal acquisition and data process. The oscillating frequency of the quartz crystal decreases on adsorption of organic molecules on the coating materials. The principal component analysis (PCA) method with SAS software was applied to select the appropriate coating materials onto the SAW crystals for organic vapors, e.g. hexane, 1‐hexene, 1‐hexyne, 1‐propanol, propionaldehyde, propionic acid, and 1‐propylamine. A dataset for a multi‐channel sensor with 19 SAW crystals for 7 analyses was collected after comparing the correlation between the 19 coating materials and the first six principal component (PC) factor. Furthermore, linear discriminate analysis (LDA) with SPSS software and a profile discrimination map were also applied and discussed for the discrimination of these organic vapors. These organic molecules could be clearly distinguished by the six‐channel SAW static sensor. The effect of concentration for various organic vapors was investigated and discussed.     

The Evolution of Bonding and Thermodynamic Properties of Boron‐Doped Small Carbon Clusters: An Ab Initio Study

Theoretical studies on BC_n (n=1–6) clusters are carried out using density functional theory, Møller–Plesset second‐order perturbation theory (MP2), coupled‐cluster calculations including up to triple excitations (CCSD(T)), and higher‐level approaches. All possible isomers depending on the positions of the boron atom are generated and the lowest‐energy isomers are determined for doublet and quartet electronic states. The three potential evolution paths of the clusters are determined as a function of their size. The energetic and electronic consequences for the increased size of structures differ significantly, which leads to representatives of the ground electronic state from different structural groups. The ab initio calculated thermal functions allow enhancements to the available atomization energies and improve the agreement between the calculated and experimental heat content.     

Multi‐Dimensional Cobalt(II) and Nickel(II) Coordination Polymers

A series of metal coordination polymers, [Co₂(NB)₄(bpp)₂(H₂O)]·H₂O ( 1 ), [Co₂(e,e‐trans‐chdc)(e,a‐cis‐chdc)(bpp)₂] ( 2 ), [Ni(e,e‐trans‐chdc)(bpp)(H₂O)₂] ( 3 ), [Ni₂(PDA)₂(bpp)₂(H₂O)₃]·H₂O ( 4 ), and [Ni‐(mBDC)(bpp)] ( 5 ) (NB = 3‐nitrobenzoate anion; bpp = 4,4′‐trimethylene dipyridine; chdc = cyclohexane‐1,4‐dicarboxylate anion; PDA = 1,4‐phenylenediacetate anion; mBDC = 1,3‐benzene dicarboxylate anion), were synthesized from metal ions and organic mixed‐ligands by hydrothermal reactions. The single crystal structure analysis revealed that 1, 3, and 4 were 2D sheets with bilayer (1 and 4) and 2‐fold interpenetrated layers (3), 2 is a 3D binodal (4,5)‐connected framework, and 5 is a 1D chains. The non‐covalent interactions of H‐bonds and π–π stacking caused this conformation of highly cross‐linked networks. Compounds 1‐5 were further characterized by thermal gravimetric analysis, powder X‐ray diffraction, UV‐vis, infrared, and PL spectroscopy.     

The NICS‐XY‐Scan: Identification of Local and Global Ring Currents in Multi‐Ring Systems

Nucleus‐independent chemical shift (NICS)‐based methods are very popular for the determination of the induced magnetic field under an external magnetic field. These methods are used mostly (but not only) for the determination of the aromaticity and antiaromaticity of molecules and ions, both qualitatively and quantitatively. The ghost atom that serves as the NICS probe senses the induced magnetic field and reports it in the form of an NMR chemical shift. However, the source of the field cannot be determined by NICS. Thus, in a multi‐ring system that may contain more than one induced current circuit (and therefore more than one source of the induced magnetic field) the NICS value may represent the sum of many induced magnetic fields. This may lead to wrong assignments of the aromaticity (and antiaromaticity) of the systems under study. In this paper, we present a NICS‐based method for the determination of local and global ring currents in conjugated multi‐ring systems. The method involves placing the NICS probes along the X axis, and if needed, along the Y axis, at a constant height above the system under study. Following the change in the induced field along these axes allows the identification of global and local induced currents. The best NICS type to use for these scans is NICS_πZZ, but it is shown that at a height of 1.7 Å above the molecular plane, NICS_ZZ provides the same qualitative picture. This method, namely the NICS‐XY‐scan, gives information equivalent to that obtained through current density analysis methods, and in some cases, provides even more details.     

Amphiphilic Polymethacrylate‐ and Polystyrene‐Based Chemical Delivery Systems for Damascones

Amphiphilic polystyrene‐ and polymethacrylate‐based β‐acyloxy ketones were investigated as potential delivery systems for the controlled release of damascones by retro‐1,4‐addition in applications of functional perfumery. A series of random copolymers being composed of the hydrophobic damascone‐release unit and a second hydrophilic monomer were obtained by radical polymerization in organic solution by using 2,2′‐azobis[2‐methylpropanenitrile] (AIBN) as the radical source (Schemes 2 and 3). A first evaluation of the polymer conjugates in acidic or alkaline buffered aqueous solution, and in the presence of a surfactant, showed that polymethacrylates and polystyrenes having a carboxylic acid function as hydrophilic group are particularly interesting for the targeted applications (Table 2). The release of δ‐damascone ( 1 ) from polymers with poly(methacrylic acid) and poly(vinylbenzoic acid) comonomers in different stoichiometric ratios was thus followed over several days at pH 4, 7, and 9 by comparison of fluorescence probing, solvent extraction, and particle‐size measurements (Tables 3 and 4). In acidic media, the polymers were found to be stable, and almost no δ‐damascone ( 1 ) was released. In neutral or alkaline solution, where the carboxylic acid functions are deprotonated, the concentration of 1 increased over time. In the case of the polymethacrylates, the fluorescence probing experiments showed an increasing hydrophilicity of the polymer backbone with increasing fragrance release, whereas in the case of the polystyrene support, the hydrophilicity of the environment remained constant. These results suggest that the nature of the polymer backbone may have a stronger influence on the fragrance release than the ratio of hydrophilic and hydrophobic monomers in the polymer chain.     

Photo‐Tethers for the (Multi‐)Cyclic,Conformational Caging of Long Oligonucleotides

Intramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne‐modified photolabile nucleosides into DNA sequences, followed by a Cu^I‐catalyzed alkyne–azide cycloaddition with bis‐azido linker molecules. We determined a range of ring sizes, in which the caged circular oligonucleotides exhibit superior duplex destabilizing properties. Specific binding of a full‐length 90 nt C10 aptamer recognizing human Burkitt's lymphoma cells was then temporarily inhibited by locking the aptamer in a bicircularized structure. Irradiation restored the native aptamer conformation resulting in efficient cell binding and uptake. The photo‐tether strategy presented here provides a robust and versatile tool for the light‐activation of longer functional oligonucleotides, noteworthy without prior knowledge on the structure and the importance of specific nucleotides within a DNA aptamer.     

Photo‐Tethers for the (Multi‐)Cyclic,Conformational Caging of Long Oligonucleotides

Intramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne‐modified photolabile nucleosides into DNA sequences, followed by a Cu^I‐catalyzed alkyne–azide cycloaddition with bis‐azido linker molecules. We determined a range of ring sizes, in which the caged circular oligonucleotides exhibit superior duplex destabilizing properties. Specific binding of a full‐length 90 nt C10 aptamer recognizing human Burkitt's lymphoma cells was then temporarily inhibited by locking the aptamer in a bicircularized structure. Irradiation restored the native aptamer conformation resulting in efficient cell binding and uptake. The photo‐tether strategy presented here provides a robust and versatile tool for the light‐activation of longer functional oligonucleotides, noteworthy without prior knowledge on the structure and the importance of specific nucleotides within a DNA aptamer.     

Contra‐Thermodynamic,Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two‐Dimensional Chemical Space

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z‐α‐substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp²)?B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E‐α‐substituted styrenyl BPins to generate the corresponding Z‐isomers with high fidelity. Preliminary validation of this contra‐thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z‐configured trisubstituted alkenes, as well as in a concise synthesis of the anti‐tumor agent Combretastatin A4.     

Contra‐Thermodynamic,Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two‐Dimensional Chemical Space

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z‐α‐substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp²)−B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E‐α‐substituted styrenyl BPins to generate the corresponding Z‐isomers with high fidelity. Preliminary validation of this contra‐thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z‐configured trisubstituted alkenes, as well as in a concise synthesis of the anti‐tumor agent Combretastatin A4.