Porosity Switching in Polymorphic Porous Organic Cages with Exceptional Chemical Stability

Porous solids that can be switched between different forms with distinct physical properties are appealing candidates for separation, catalysis, and host–guest chemistry. In this regard, porous organic cages (POCs) are of profound interest because of their solution‐state accessibility. However, the application of POCs is limited by poor chemical stability. Synthesis of an exceptionally stable imine‐linked (4+6) porous organic cage ( TpOMe‐CDA ) is reported using 2,4,6‐trimethoxy‐1,3,5‐triformyl benzene (TpOMe) as a precursor aldehyde. Introduction of the ‐OMe functional group to the aldehyde creates significant steric and hydrophobic characteristics in the environment around the imine bonds that protects the cage molecules from hydrolysis in the presence of acids or bases. The electronic effect of the ‐OMe group also plays an important role in enhancing the stability of the reported POCs. As a consequence, TpOMe‐CDA reveals exceptional chemical stability in neutral, acidic and basic conditions, even in 12 m NaOH. Interestingly, TpOMe‐CDA exists in three different porous and non‐porous polymorphic forms (α, β, and γ) with respect to differences in crystallographic packing and the orientation of the flexible methoxy groups. All of the polymorphs retain their crystallinity even after treatment with acids and bases. All the polymorphs of TpOMe‐CDA differ significantly in their properties as well as morphology and could be reversibly switched in the presence of an external stimulus.     

Photocatalytic Organic Syntheses: Selective Cyclization of Amino Acids in Aqueous Suspensions

Photocatalytic reactions occurring at semiconductor particles/solution interfaces can be applied to organic syntheses. In this review article, examples of photocatalytic syntheses of cyclic amino acids by suspended semiconductor particles, e.g., titanium(IV) oxide or cadmium(II) sulfide are introduced and interpreted. Different from the photocatalytic decomposition of pollutants under aerobic conditions, selective conversion of organic compounds can be driven by the photocatalytic reactions under deaerated conditions.     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

An extensive study on isosorbide-5-mononitrate acid adducts for quantification in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry and its application to bioequivalence sample analysis

A rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the determination of isosorbide-5-mononitrate (5-ISMN), used in the treatment of angina pectoris, in human plasma is described. The quantification of 5-ISMN was performed via stable acetate adduct formation with a high relative abundance. The plasma filtrate obtained after solid-phase extraction (SPE), using a polymer based, hydrophilic-lipophilic balanced (HLB) cartridge, was submitted directly to reversed-phase high-performance liquid chromatography separation followed by ESI and detection of the resulting ions using triple-quadrupole mass spectrometry in selected reaction monitoring (SRM) mode. There was no significant matrix effect on the analysis. For validation of the method, the recovery of the free analyte response was compared to that obtained from an optimized extraction method. The analyte stability was examined under conditions mimicking the sample storage, handling, and analytical procedures. The extraction procedure yielded extremely clean extracts with a recovery of 95.51% and 93.98% for iossorbide-5-mononitrate and topiramate (internal standard (IS)), respectively. The calibration curves were linear for the dynamic range of 10.0 to 1000.0 ng/mL with a correlation coefficient r > or = 0.9985. The intra-assay and inter-assay precision for the samples at the lower limit of quantification (LLOQ) were 9.02 and 13.30%, respectively. The intra-assay accuracies at LLOQ, LQC, MQC and HQC levels varied from 98.13 to 118.15, 102.34 to 105.21, 100.69 to 109.68, and 95.76 to 102.92%, respectively, while the inter-assay accuracies ranged from 93.10 to 118.15, 93.03 to 107.04, 86.97 to 109.68 and 86.18 to 105.85%, respectively, at these levels. The method is rugged and fast with a total run time of 2 min. The method was successfully applied for a bioequivalence study in 24 human subject samples after oral administration of 60 mg extended release (ER) formulations.     

Study of approximate coupled cluster methods for first-order static properties

In this paper, we analyse the algebraic structure of the equations for calculating the first order static properties using several approximate versions of Coupled Cluster (CC) methods. In particular, the non-variational and the variational method using a CC wavefunction corresponding to an appropriately defined perturbed Hamiltonian as well as the simple expectation value expression using a CC stationary state are studied under different approximations. Two different models are proposed: (a) use of maximum overlap orbitals where the pertinent approximations are TT ₂, T ⁽¹⁾ T ₂ ⁽¹⁾, (b) use of Hartree-Fock orbitals and T(T ₁+T ₂), T ⁽¹⁾(T ₁ ⁽¹⁾ +T ₂ ⁽¹⁾ ) approximations. It is analytically shown that in both these models certain approximate versions of the methods under purview yield identical results for first order static properties.NCL Communication No. 3725     

Lanthanide-mediated supramolecular cages and host-guest interactions

The structure and thermodynamic properties of lanthanide complexes with a new tripodal ligand L2 have been elucidated using different physicochemical methods. At stoichiometric ratios, the tetrahedral three-dimensional complexes with lanthanide cations are formed in acetonitrile with good stabilities. Despite minor structural changes comparing to previously investigated tripodal ligands, the resulting assembly exhibits different features revealed with the crystal structure of [Eu(4)L2(4)](OH)(ClO(4))(11) (orthorhombic, Pbcn). Interestingly, the highly charged edifice contains an inner cage encapsulating a perchlorate anion. Such lanthanide mediated cage-like assemblies are rare, and may be of interest for different sensing applications. Indeed, the anionic guest can be exchanged with different anions. The related host-guest equilibria were investigated with NMR techniques. Various aspects of these reactions are qualitatively discussed.     

AlCl3 induced C-N bond formation followed by Pd/C-Cu mediated coupling-cyclization strategy: synthesis of pyrrolo[2,3-b]quinoxalines as anticancer agents

AlCl₃ facilitated C-N bond forming reaction between 2,3-dichloroquinoxaline and anilines affording a convenient method for the preparation of N-aryl substituted 3-chloroquinoxalin-2-amines. A related N-benzyl derivative, however, was prepared via a conventional method. These N-alkyl/aryl substituted 3-chloroquinoxalin-2-amines on coupling with terminal alkynes in toluene under Pd/C-Cu catalysis afforded a range of 1,2-disubstituted pyrrolo[2,3-b]quinoxalines within 3-5 h in good to excellent yields. Some of the compounds synthesized showed promising anti-proliferative properties when tested in vitro against two cancer cell lines. Docking studies indicated that these molecules interact well with human Akt in silico.