Organometallic polymers. XXIV. Radical-initiated copolymerization of ferrocenylmethyl acrylate and methacrylate with acrylonitrile,maleic anhydride,and N-vinyl-2-pyrrolidone

Ferrocenylmethyl acrylate (I) and ferrocenylmethyl methacrylate (II) have been readily copolymerized with maleic anhydride in benzene–ethyl acetate solutions. Similarly, II has been copolymerized with both acrylonitrile and N-vinyl-2-pyrrolidone in benzene solutions to give higher molecular weight copolymers in high yields. In all cases azobisisobutyronitrile has been the initiator. Based on e values obtained, the metal carbonyl substituent acts as an electron-withdrawing group. Over a wide range of comonomers (N-vinyl-2-pyrrolidone, styrene, vinyl acetate, methyl acrylate, acrylonitrile, and maleic anhydride) I and II exhibit r₁ values lower than (and r₂ values higher than) similar copolymerizations with methyl acrylate or methyl methacrylate. Further more, the Q values found for I (0.03–0.11) and II (0.08–0.18) are smaller than those for methyl acrylate (0.46) and methyl methacrylate (0.74). Thus, I and II are less reactive than expected, presumably due to steric effects.     

Coupling of bulky,electron-deficient partners in aryl amination in the preparation of tridentate bis(oxazoline) ligands for asymmetric catalysis

A new class of tridentate bis(oxazoline) ligands 7, in which an N-phenylaniline unit links the two oxazoline rings, has been prepared. The key step in their synthesis is a Hartwig-Buchwald type Pd-catalyzed aryl amination between the two bulky o-substituted coupling partners, 2-(2'-bromophenyl)oxazolines 8 and 2-(o-aminophenyl)oxazolines 9. By varying the substituent on the coupling partners, a range of 10 ligands has been prepared in good yield. During the synthesis of 2-(o-aminophenyl)oxazolines 9a-d, a number of products of unexpected side reactions were isolated in two of the three steps. Alternatively, the required 2-(o-aminophenyl)oxazolines 9 were obtained by a DAST-promoted cyclodehydration of hydroxyamides 12a-d without formation of any byproducts.     

Organometallic polymers. XXIX. Synthesis and characterization of ferrocene-containing siloxane polymers from bis(dimethylamino)silane–disilanol condensation

A new monomer, 1,1′-bis(dimethylaminodimethylsilyl)ferrocene, was synthesized by two routes and polymerized with three aryl disilanols: dihydroxydiphenylsilane, 1,4-bis(hydroxydimethylsilyl)benzene, and 4,4′-bis(hydroxydimethylsilyl)biphenyl, yielding three different polysiloxanes. Melt polymerizations carried out at 1 torr pressure and 100°C resulted in the highest molecular weight polymers. Intramolecular cyclization competed with intermolecular chain extension in polymerization of the bis(aminosilane) with dihydroxydiphenylsilane, resulting in isolation of a bridged derivative, 1,3,5-trisila-2,4-dioxa-1,1,5,5-tetramethyl-3,3-diphenyl[5]ferrocenophane. Cyclization did not compete significantly during the formation of polymers from this bisaminosilane and the two remaining diols, as evidenced by higher yields and greater molecular weights. These polymers could be cast as tough flexible films, and fibers could be drawn from their melts. TGA and DSC data showed the polymer formed from 1,1′-bis(dimethylaminodimethylsilyl)ferrocene and 1,4-bis(hydroxydimethylsilyl)benzene to be at least as thermally stable as an arylene siloxane polymer which differed from the ferrocenylsiloxane structure only in the replacement of the ferrocene moiety with a p-substituted phenylene linkage. The ferrocene-containing polymers were generally hydrolytically stable under conditions of refluxing THF–H₂O(10 : 1) for 1 hr. The polymer-forming reaction was found to follow second-order kinetics, and the specific rate constants for formation of two of the polymers were measured.     

DNA aptamer folding on gold nanoparticles: from colloid chemistry to biosensors

We have investigated the effect of the folding of DNA aptamers on the colloidal stability of gold nanoparticles (AuNPs) to which an aptamer is tethered. On the basis of the studies of two different aptamers (adenosine aptamer and K+ aptamer), we discovered a unique colloidal stabilization effect associated with aptamer folding: AuNPs to which folded aptamer structures are attached are more stable toward salt-induced aggregation than those tethered to unfolded aptamers. This colloidal stabilization effect is more significant when a DNA spacer was incorporated between AuNP and the aptamer or when lower aptamer surface graft densities were used. The conformation that aptamers adopt on the surface appears to be a key factor that determines the relative stability of different AuNPs. Dynamic light scattering experiments revealed that the sizes of AuNPs modified with folded aptamers were larger than those of AuNPs modified with unfolded (but largely collapsed) aptamers in salt solution. From both the electrostatic and steric stabilization points of view, the folded aptamers that are more extended from the surface have a higher stabilization effect on AuNP than the unfolded aptamers. On the basis of this unique phenomenon, colorimetric biosensors have been developed for the detection of adenosine, K+, adenosine deaminase, and its inhibitors. Moreover, distinct AuNP aggregation and redispersion stages can be readily operated by controlling aptamer folding and unfolding states with the addition of adenosine and adenosine deaminase.     

Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd II-catalyzed ring-opening strategy

New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)-norchelidonine.     

Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.     

Gas-Phase Enrichment of Multiply Charged Peptide Ions by Differential Ion Mobility Extend the Comprehensiveness of SUMO Proteome Analyses

The small ubiquitin-like modifier (SUMO) is a member of the family of ubiquitin-like modifiers (UBLs) and is involved in important cellular processes, including DNA damage response, meiosis and cellular trafficking. The large-scale identification of SUMO peptides in a site-specific manner is challenging not only because of the low abundance and dynamic nature of this modification, but also due to the branched structure of the corresponding peptides that further complicate their identification using conventional search engines. Here, we exploited the unusual structure of SUMO peptides to facilitate their separation by high-field asymmetric waveform ion mobility spectrometry (FAIMS) and increase the coverage of SUMO proteome analysis. Upon trypsin digestion, branched peptides contain a SUMO remnant side chain and predominantly form triply protonated ions that facilitate their gas-phase separation using FAIMS. We evaluated the mobility characteristics of synthetic SUMO peptides and further demonstrated the application of FAIMS to profile the changes in protein SUMOylation of HEK293 cells following heat shock, a condition known to affect this modification. FAIMS typically provided a 10-fold improvement of detection limit of SUMO peptides, and enabled a 36% increase in SUMO proteome coverage compared to the same LC-MS/MS analyses performed without FAIMS.

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Graphical Abstract ?

     

4-Methoxypyridine-(pyridine-2,6-dicarboxylato-N,O,O′) copper(II)

The synthesis and X-ray crystal structure of [Cu(C₇H₃NO₄)(C₆H₇NO)], [Cu(dipic)(4-MeO-Py)], (dipic = pyridine-2,6-dicarboxylate, 4-MeO-Py = 4-methoxypyridine), is described. Molecules of [Cu(dipic)(4-MeO-Py)] are formed {via} coordination of the copper(II) cation to two nitrogen atoms, from the dipic and 4-MeO-Py ligands respectively, and to two oxygen atoms from the carboxylate groups of the dipic ligand. The molecules pack in a non-centrosymmetric manner, stacked eclipsed with respect to one another along the b-axis and aligned parallel in a head-to-tail motif. The title compound crystallizes in the orthorhombic space group, Pca2(1), with a = 27.339(3) Å, b = 3.7130(4) Å, c = 11.6859(12) Å, V = 1186.2(2) ų, and Z = 4. The structure was solved by direct methods and refined by least-squares methods to a final R-factor of 0.0327 for 2648 independent reflections.