Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids.

The use of transdermal delivery for nucleic acid administration is an interesting approach to overcoming limitations of systemic administration routes, such as first-pass effects, the painful needle injection, or their poor biodistribution. Thus, the use of a microneedle-based patch could represent a turning point for nucleic acid delivery, thanks to the possibility of self-administration of the actives in a painless and easy procedure. However, the design of transdermal systems with a higher degree of precision release is a clear need that has not been fully resolved.

From propenolysis to enyne metathesis: tools for expedited assembly of 4,8-azaboranaphthalene and extended polycycles with embedded BN.

The synthesis of BN-containing molecules, which have an interesting isosteric relationship to their parent all-C cores, has drawn a great deal of attention as an avenue to alter and tune molecular function. Nevertheless, many cores with embedded BN are still hard to synthesize, and thus, further effort is required in this direction. Herein, we present an integrated approach to BN-containing polycycles rooted in an exceptionally clean B-N condensation of amines with a tri-allylborane.

Cyclic Homo- and Heterohalogen Di-λ-diarylhalonium Structures.

In the context of the ever-growing interest in the cyclic diaryliodonium salts, this work presents synthetic design principles for a new family of structures with two hypervalent halogens in the ring. The smallest bis-phenylene derivative, [(CH)I], was prepared through oxidative dimerization of a precursor bearing the -disposed iodine and trifluoroborate groups. We also report, for the first time, the formation of cycles containing two different halogen atoms.

Ammonium trifluoroborate-modified poly(β-aminoesters): A case study for PET-guided in vivo pharmacokinetic studies of a non-viral gene delivery system.

Nucleic acid-based therapies have become a game-changing player in our way of conceiving pharmacology. Nevertheless, the inherent lability of the phosphodiester bond of the genetic material with respect to the blood nucleases severely hampers its delivery in naked form, therefore making it necessary to use delivery vectors. Among the potential non-viral vectors, polymeric materials such as the poly(β-aminoesters) (PBAEs) stand out as promising gene carriers thanks to their ability to condense nucleic acids in the form of nanometric polyplexes.

PET Imaging of Self-Assembled F-Labelled Pd L Metallacages for Anticancer Drug Delivery.

To advance the design of self-assembled metallosupramolecular architectures as new generation theranostic agents, the synthesis of F-labelled [Pd L ] metallacages is reported. Different spectroscopic and bio-analytical methods support the formation of the host-guest cage-cisplatin complex. The biodistribution profiles of one of the cages, alone or encapsulating cisplatin have been studied by PET/CT imaging in healthy mice in vivo, in combination to ICP-MS ex vivo.

Large-Scale Monitoring of the Frequency of Ryanodine Receptor Target-Site Mutations Conferring Diamide Resistance in Brazilian Field Populations of Fall Armyworm, (Lepidoptera: Noctuidae).

Fall armyworm (FAW), , is an important lepidopteran pest in the Americas, and recently invaded the Eastern Hemisphere. In Brazil, FAW is considered the most destructive pest of corn and cotton. FAW has evolved resistance to many insecticides and (Bt) proteins.

Expanding the Diversity at the C-4 Position of Pyrido[2,3-]pyrimidin-7(8)-ones to Achieve Biological Activity against ZAP-70.

Pyrido[2,3-]pyrimidin-7(8)-ones have attracted widespread interest due to their similarity with nitrogenous bases found in DNA and RNA and their potential applicability as tyrosine kinase inhibitors. Such structures, presenting up to five diversity centers, have allowed the synthesis of a wide range of differently substituted compounds; however, the diversity at the C4 position has mostly been limited to a few substituents. In this paper, a general synthetic methodology for the synthesis of 4-substituted-2-(phenylamino)-5,6-dihydropyrido[2,3-]pyrimidin-7(8)-ones is described.

Exploring benzylic -C(sp)-boron-silicon and boron-tin centers as a synthetic platform.

A stepwise build-up of multi-substituted C carbon centers is an attractive, conceptually simple, but often synthetically challenging type of disconnection. To this end, this report describes how -α,α-dimetalloid-substituted benzylic reagents bearing boron/silicon or boron/tin substituent sets are an excellent stepping stone towards diverse substitution patterns. These -dimetalloids were readily accessed, either by known carbenoid insertion into C-B bonds or by the newly developed scalable deprotonation/metallation approach.

The Versatile Reaction Chemistry of an Alpha-Boryl Diazo Compound.

The first α-boryl diazo compound that is capable of engaging in classic synthetic organic diazo reaction chemistry is described. The diazomethyl-1,2-azaborine , which is a BN isostere of phenyldiazomethane, is significantly more stable than phenyldiazomethane; its reaction chemistry ranges from C-H activation, O-H activation, [3+2] cycloaddition, and halogenation, to Ru-catalyzed carbonyl olefination. The demonstrated broad range of reactivity of diazomethyl-1,2-azaborine makes it an exceptionally versatile synthetic building block for the 1,2-azaborine heterocyclic motif.

Boron-Wittig olefination with gem-bis(boryl)alkanes.

The condensation of easy manageable lithium α-bis(boryl)carbanions with carbonyl derivatives, the so-called boron-Wittig reaction, allows for the straightforward and often stereoselective formation of synthetically highly versatile metalloid-substituted alkenes, which are key building blocks on route to all-carbon substituted olefins. In this Tutorial review the concept behind this olefination reaction and its application to ketones, aldehydes and other carbonyl derivatives, such amides, ester and carboxylic acids, are presented in a systematic manner. A special emphasis has been placed on parameters controlling the stereochemical outcome of these transformations.

Iodane-Guided ortho C-H Allylation.

A metal-free C-H allylation strategy is described to access diverse functionalized ortho-allyl-iodoarenes. The method employs hypervalent (diacetoxy)iodoarenes and proceeds through the iodane-guided "iodonio-Claisen" allyl transfer. The use of allylsilanes bearing electron-withdrawing functional groups unlocks the functionalization of a broad range of substrates, including electron-neutral and electron-poor rings.

The Power of Iodane-Guided C-H Coupling: A Group-Transfer Strategy in Which a Halogen Works for Its Money.

Hypervalent organoiodane reagents are ubiquitous in organic synthesis, both as oxidants and as electrophilic group-transfer agents. In addition to these hallmark applications, a complementary strategy is gaining momentum that exploits the ability of λ -iodanes to undergo iodine-to-arene group transfer, for example, via iodonio-Claisen-type rearrangement processes. This Minireview discusses recent advances in the use of this method to access a variety of the C-H-functionalized iodoarenes.

Transition-metal-free B-B and B-interelement reactions with organic molecules.

This review is a guided tour along the activation modes and reactivity of B-B, B-Si, B-N, B-S, B-Se and B-P reagents, in the absence of any transition metal complex. Here are disclosed the general concepts related to the homolytic and heterolytic cleavage of B-B and B-interelement bonds, as well as the generation of new C-B and C-interelement bonds, in a selective way. The greener consequences of these novel routes facilitate the gram scale preparations of target functionalised organic compounds.

Opportune gem-Silylborylation of Carbonyl Compounds: A Modular and Stereocontrolled Entry to Tetrasubstituted Olefins.

An easy access to highly versatile gem-silylboronate synthons is achieved by means of a new olefination reagent, HC(Bpin) (SiMe ). Subsequent silicon or boron-based selective functionalization allows for the modular and stereocontrolled synthesis of all-carbon tetrasubstituted alkenes. A particular attraction of this approach is the iododesilylation reaction, which becomes a pivotal tool for C-Si functionalization.

Strategic Trimethylsilyldiazomethane Insertion into pinB-SR Followed by Selective Alkylations.

The insertion of the diazo derivative Me3SiCHN2 into pinB-SR σ bonds (R = Ph, Tol, Bn) allows a direct synthesis of multisubstituted H-C(SR)(Bpin)(SiMe3) compounds. Consecutive base-assisted transformations of HC(S)(B) (Si) systems lead to deborylative alkylations, Sommelet-Haüser rearrangements, and deprotoalkylations. Intramolecular cyclizations can be selectively performed either via desilylative or deborylative manifolds by fine-tuning the base employed.

Synthesis of a Naphthodiazaborinine and Its Verification by Planarization with Atomic Force Microscopy.

Aiming to study new motifs, potentially active as functional materials, we performed the synthesis of a naphthodiazaborinine (the BN isostere of the phenalenyl anion) that is bonded to a hindered di-ortho-substituted aryl system (9-anthracene). We used atomic force microscopy (AFM) and succeeded in both the verification of the original nonplanar structure of the molecule and the planarization of the skeleton by removing H atoms that cause steric hindrance. This study demonstrated that planarization by atomic manipulation is a possible route for extending molecular identification by AFM to nonplanar molecular systems that are difficult to probe with AFM directly.

Undeniable Confirmation of the syn-Addition Mechanism for Metal-Free Diboration by Using the Crystalline Sponge Method.

The stereochemical outcome of the recently developed metal-free 1,2-diboration of aliphatic alkenes has, until now, only been elucidated by indirect means (e.g. derivatization).

Correction: Unsymmetrical 1,1-diborated multisubstituted sp(3)-carbons formed via a metal-free concerted-asynchronous mechanism.

Correction for 'Unsymmetrical 1,1-diborated multisubstituted sp(3)-carbons formed via a metal-free concerted-asynchronous mechanism' by Ana B. Cuenca et al., Org.

Unsymmetrical 1,1-diborated multisubstituted sp(3)-carbons formed via a metal-free concerted-asynchronous mechanism.

We have experimentally proved the unsymmetrical 1,1-diboration of diazo compounds, formed in situ from aldehydes and cyclic and non-cyclic ketones, in the absence of any transition metal complex. The heterolytic cleavage of the mixed diboron reagent, Bpin-Bdan, and the formation of two geminal C-Bpin and C-Bdan bonds has been rationalised based on DFT calculations to occur via a concerted-asynchronous mechanism. Diastereoselection is attained on substituted cyclohexanones and DFT studies provide understanding on the origin of the selectivity.

Gold(I)-catalysed cascade reactions in the synthesis of 2,3-fused indole derivatives.

A gold(I)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3-unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction.

Mixed diboration of alkenes in a metal-free context.

Experimental and theoretical rationalization on regioselective mixed diboration of alkenes, with the unsymmetrical diboron reagent Bpin-Bdan, providing the protecting Bdan moiety in the internal position.

FeCl3·6H2O-catalyzed Mukaiyama-aldol type reactions of enolizable aldehydes and acetals.

Mukaiyama-aldol type reactions of acetals derived from enolizable aldehydes with FeCl3·6H2O, an eco-friendly, low-cost, and stable catalyst, lead to β-methoxycarbonyl compounds with nearly quantitative yields. The methodology is extended to the parent aldehydes as starting materials, leading to the corresponding aldols with lower yields, but efficiently. Different alkyl and aryl substituted acetals and aldehydes have been tested in the reaction with linear and cyclic silyl enol ethers.

Competitive gold-activation modes in terminal alkynes: an experimental and mechanistic study.

The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species.

Osmium(III) complexes with POP pincer ligands: preparation from commercially available OsCl(3)·3H(2)O and their X-ray structures.

Complexes OsCl(3){dbf(P(i)Pr(2))(2)} [1; dbf(P(i)Pr(2))(2) = 4,6-bis(diisopropylphosphino)dibenzofuran], OsCl(3){xant(P(i)Pr(2))(2)} [2; xant(P(i)Pr(2))(2) = 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene], and OsCl(3){xant(PPh(2))(2)} [3; xant(PPh(2))(2) = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene] have been obtained in high yield by the reaction of the corresponding diphosphine with OsCl(3)·3H(2)O. The ruthenium(III) counterparts RuCl(3){dbf(P(i)Pr(2))(2)} (4), RuCl(3){xant(P(i)Pr(2))(2)} (5), and RuCl(3){xant(PPh(2))(2)} (6) are similarly obtained from RuCl(3)·3H(2)O in moderate yields. The X-ray structures of dbf(P(i)Pr(2))(2) and complexes 1-3 are also reported.