Photocontrolled Release of the Anticancer Drug Chlorambucil with Caged Harmonic Nanoparticles

While chemotherapy is one of the most used treatments in oncology, the systemic administration of chemotherapeutics generally results in undesired damages to healthy tissues and cells, side effects such as severe nausea and leukopenia, and reduced efficacy due to multidrug resistance and poor target accessibility. The limitations of conventional chemotherapy formulation have prompted the development of alternative nanomaterials-based strategies to achieve targeted and stimuli sensitive payload delivery to reach optimal local drug concentration at tumor sites. In this study, the anticancer drug chlorambucil (Clb) was conjugated to the surface of silica coated lithium niobate (LNO) harmonic nanoparticles (HNPs) using a photocaging tether based on coumarin-4-yl methyl derivative. Upon laser pulsed femtosecond irradiation at 790 nm, the second harmonic emission from the metal oxide core induced the efficient release of Clb, with concomitant contribution from the nonlinear absorption of the coumarin (CM)-based moiety.     

On the Effect of Tether Composition on cis/trans Selectivity in Intramolecular Diels–Alder Reactions

Intramolecular Diels–Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6‐31+G(d) and CBS‐QB3 levels of theory for a series of 1,3,8‐nonatrienes, H₂C?CH? CH?CH? CH₂? X? Z? CH?CH₂ [? X? Z? =? CH₂? CH₂? ( 1 ); ? O? C(?O)? ( 2 ); ? CH₂? C(?O)? ( 3 ); ? O? CH₂? ( 4 ); ? NH? C(?O)? ( 5 ); ? S? C(?O)? ( 6 ); ? O? C(?S)? ( 7 ); ? NH? C(?S)? ( 8 ); ? S? C(?S)? ( 9 )]. For each system studied ( 1 – 9 ), cis‐ and trans‐TS isomers, corresponding, respectively, to endo‐ and exo‐positioning of the ? C? X? Z? tether with respect to the diene, have been located and their relative energies (E_rel^TS) employed to predict the cis/trans IMDA product ratio. Although the E_rel^TS values are modest (typically <3 kJ mol^?1), they follow a clear and systematic trend. Specifically, as the electronegativity of the tether group X is reduced (X?O→NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis‐TS, namely (1) unfavorable torsional (eclipsing) strain about the C4? C5 bond, that is caused by the ? C? X? C(?Y)? group’s strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo‐(thio)carbonyl group, C?Y, and the diene. The former interaction predominates when X is weakly electronegative (X?N, S), while the latter is dominant when X is more strongly electronegative (X?O), or a methylene group (X?CH₂) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1 , 2 , 3 , and 4 (published work) and 5 , 6 , and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans‐selectivities in IMDAs that are normally only weakly selective. Experimental verification of the validity of this claim comes in the form of fumaramide 14 , which undergoes a more trans‐selective IMDA reaction than the corresponding ester tethered precursor 13 .     

Nonlinear dynamics of flexible tethered satellite system subject to space environment

The paper studies the nonlinear dynamics of a flexible tethered satellite system subject to space environments, such as the J ₂ perturbation, the air drag force, the solar pressure, the heating effect, and the orbital eccentricity. The flexible tether is modeled as a series of lumped masses and viscoelastic dampers so that a finite multidegree-of-freedom nonlinear system is obtained. The stability of equilibrium positions of the nonlinear system is then analyzed via a simplified two-degree-freedom model in an orbital reference frame. In-plane motions of the tethered satellite system are studied numerically, taking the space environments into account. A large number of numerical simulations show that the flexible tethered satellite system displays nonlinear dynamic characteristics, such as bifurcations, quasi-periodic oscillations, and chaotic motions.     

空间电动力绳系统理论及实验研究

本文关注在轨航天器中具有导电性能的电动力绳系统,因其复杂动响应特征及潜在应用前景值得学者们深入研究。论文阐述了电动力绳系统的工作原理,对系统的力学建模、动力学行为、控制、应用、在轨实验及地面实验方法等研究进展进行了详细总结,同时提出电动力绳系统有待进一步探究的科学与技术问题。     

High‐valent Molybdenum Imido Complexes with Tethered Olefins

Against the background of the (propene)Mo(=O)(=NH) and (allyl)Mo(=O)(=NH) surface species suggested as intermediates of the SOHIO process the potential of H₂N–C₆H₄–CH₂– CH=CH–CH₃, ( I ), for the introduction of chelating imido/olefin or imido/allyl ligands at highvalent Mo centres was tested. Reaction of I with Na₂[MoO₄] and trimethylchlorosilane yielded [Cl₂Mo(=N–C₆H₄–CH₂–CH=CH–CH₃)₂(dme)] ( 1 ), containing pendant olefinic arms. All attempts to introduce the olefin into the coordination sphere of the Mo centre failed. The same observation was made with [Cl₂Mo(=O)(=N–C₆H₄–CH₂–CH=CH–CH₃)(dme)] ( 2 ), synthesised via a commutation reaction from 1 and[(dme)Cl₂Mo(=O)₂]. Reaction of three equivalents of I with [CpMoCl_4′] yields [CpCl₂Mo(=N–C₆H₄–CH₂–CH=CH–CH₃)], ( 3 ), again with a pendant olefin arm; the products of experiments aiming at coordinating it to the Mo atom eluded isolation. I thus does not seem suitable for the synthesis of complexes with imido/olefin or imido/allyl ligands. However, products 1 – 3 , (two of which ( 1 , 3 ) were also characterised by single crystal X‐ray diffraction) are nevertheless interesting, e.g., with respect to the grafting of molybdenum complexes on the surfaces of solid supports to obtain heterogeneous oxidation catalysts.     

Lagrangian description and numerical analysis of a discrete model of flexible systems

An approach is proposed to derive the equations of motion for one-dimensional discrete-continuous flexible systems with one-sided deformation characteristics. To implement this approach, the stationarity principle is generalized to dynamic problems. Solution algorithms are based on cubic spline functions. The capabilities of the approach are demonstrated by the example of a beacon buoy connected by a flexible tether to a submersible that moves along a prescribed trajectory.__________Translated from Prikladnaya Mekhanika, Vol. 40, No. 12, pp. 107–116, December 2004.     

Synthesis of the C12-C24 fragment of peloruside A by silyl-tethered diastereomer-discriminating RCM

The C12-C24 fragment of peloruside A has been synthesized using, as a key step, a silyl-tethered ring closing metathesis reaction to form the C16-C17 (Z)-alkene. The metathesis reaction discriminates between diastereoisomers of the starting material. A diphenylsilyl bis-ether provides simultaneous protection for the C15 and C24 hydroxyl groups, and is expected to lead to high 1,5-anti selectivity in subsequent aldol reactions of the methyl ketone, allowing for a convergent stereoselective synthesis of peloruside A.     

New concepts for regio- and stereoselective bis- and triscyclopropanations of C60

The synthesis of isomerically multiple adducts of C(60) with a defined three-dimensional structure is still one of the most challenging tasks of exohedral fullerene chemistry. The inherent regioselectivity of successive additions of addends such as malonates to the fullerene's [6,6]-double bonds is only moderate. In most cases difficult-to-isolate mixtures of regioisomers are obtained. The regioselectivity can be significantly improved if multifunctional addends able to undergo two or more additions are allowed to react with C(60). Preorganization and minimization of strain energy within the addend skeleton reduce the number of sterically allowed addition patterns. Improved concepts for highly regio- and stereoselective bis- and triscyclopropanations of C(60) are described. Two examples of the bisadditions with complete regioselectivity leading to trans-2- and cis-2 are presented. Here, the two malonate binding sites are linked by rigid tetraphenylporphyrin and calix-[4]-arene spacers. Selective trisadditions were achieved with the easy-to-synthesize and easy-to-modify tripodal addends 5-7, where the malonates are held together by a focal aryl moiety. Another very elegant approach for bis- and trisadditions involves cyclo-[n]-alkylmalonates. Selection between addition patterns with and without rotational axes is possible by choosing the right combinations of the flexible alkyl chains connecting the malonates. If alkyl chains of identical lengths are used bis- and trisadducts such as 19-21 and 25 with rotational symmetry are formed with high regioselectivity. These addition patterns are avoided if cyclo-[n]-malonates containing alkyl chains of different lengths are employed. In this case adducts such as 26 and 27 with C(s)-symmetry are formed. The use of the chiral cyclo-[3]-malonate 28 allows for the regio- and stereoselective synthesis of the enantiomerically pure e,e,e-trisadducts 29 and 30 containing an inherently chiral addition pattern with C(3)-symmetry.     

Indole Synthesis through Sequential Electrophilic N−H and C−H Bond Activation Using Iodine(III) Reactivity

An intramolecular approach towards the regioselective construction of 2,3‐diarylated indoles is reported. The reaction follows an intramolecular electrophilic N?H and C?H bond functionalization between the aniline and acetylene. This methodology employs the concept of a traceless tether to provide access to the free 2,3‐diarylated indole products comprising a total of 18 examples. Hypervalent iodine reagents were identified as suitable promoters and four different protocols are provided, including stoichiometric and catalytic transformations.     

Piperidine‐appended imidazolium ionic liquids as task‐specific catalysts: computational study,synthesis, and multinuclear NMR

Imidazolium ionic liquids (IMILs) with a piperidine moiety appended via variable length methylene spacers (with n = 1–4) were studied computationally to assess their potential to act as internal base for N‐heterocyclic carbene (NHC) generation. Proton transfer energies computed by B3LYP/6‐311+G(2d,p) were least endothermic for the basic‐IL with n = 3, whose optimized structure showed the shortest C₂‐H‐‐‐‐N(piperidine) distance. Inclusion of counter anion (Cl or NTf₂) caused dramatic conformational changes to enable close contact between the acidic C₂‐H and the anions. To examine the prospect for internal C₂‐H‐‐‐‐N coordination, multinuclear NMR data (¹H, ¹⁵N, and ¹³C) were computed by gauge independent atomic orbitals–density functional theory (GIAO‐DFT) in the gas phase and in several solvents by the PCM method for comparison with the experimental NMR data for the basic ILs (with n = 2–4) synthesized in the laboratory. These studies indicate that interactions with solvent and counter ion are dominant forces that could disrupt internal C₂‐H‐‐‐‐N coordination/proton transfer, making carbene generation from these basic‐ILs unlikely without an added external base. Therefore, the piperidine‐appended IMILs appear suitable for application as dual solvent/base in organic/organometallic transformations that require the use of mild base, without the necessity to alkylate at C‐2 to prevent N‐heterocyclic carbene formation. Copyright © 2016 John Wiley & Sons, Ltd.