Recent Advances in the Development of Antibiotics-Coated Gold Nanoparticles to Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) has become an alarming threat to the successful treatment of rapidly growing bacterial infections due to the abuse and misuse of antibiotics. Traditional antibiotics bear many limitations, including restricted bioavailability, inadequate penetration and the emergence of antimicrobial-resistant microorganisms. Recent advances in nanotechnology for the introduction of nanoparticles with fascinating physicochemical characteristics have been predicted as an innovative means of defence against antimicrobial-resistant diseases. The use of nanoparticles provides several benefits, including improved tissue targeting, better solubility, improved stability, enhanced epithelial permeability and causes minimal side effects. However, except for gold nanoparticles (AuNPs), the biological safety of the majority of metal nanoparticles remains a serious problem. AuNPs appear to be promising for drug delivery and medicinal applications because of their minimal toxicity, biocompatibility, functional flexibility, chemical stability and versatile biological activities, such as their antiviral, antifungal, anti-inflammatory and antimicrobial properties. Hence, we are focusing on the gold nanoparticles possessing antimicrobial activity in this article. This review will cover recent strategies in the preparation of gold nanoparticles, with special emphasis placed on antibiotics-coated AuNPs with enhanced antimicrobial properties and how they fight against disease-causing bacteria and eradicate biofilms, along with their activities and physicochemical properties.

Copper-catalysed dehydrogenative self-coupling/cyclization of 5-aminopyrazoles: synthesis and photophysical study of pyridazines.

An interesting self-coupling/cyclization of 5-aminopyrazoles is revealed, which provides a variety of pyridazine cores in reasonable yields. In this reaction, C(sp2)-C(sp2) and N-N bond formation occurs simultaneously in one reaction vessel. The photophysical properties of the synthesized compounds were also studied and some of them exhibited fluorescence properties with good quantum yields. A radical mediated reaction mechanism is proposed with the help of control experiments.

Strategies Toward the Catalyst-Free α-C-H Functionalizations of Tertiary Amines.

α-C-H functionalization of tertiary amines has been a highly studied field for the past two decades because several important nitrogen containing heterocycles or compounds can be synthesized through this strategy. Though transition metal catalysts and some metal-free catalysts are mainly used for these reactions, a few catalyst-free reactions have recently been efficiently performed. Catalyst-free reactions are cost-effective, less sensitive to air/moisture, easier to operate, have a simple purification process, and are relatively environment-friendly. In this article, we have summarized all the α-C-H functionalization reactions of tertiary amines performed without using any external catalysts. The content of this article will undoubtedly encourage readers to do more work in this area.

Ten Years of Glory in the α-Functionalizations of Acetophenones: Progress Through Kornblum Oxidation and C-H Functionalization.

This review article focuses on the α-functionalization of acetophenones involving Kornblum oxidation and C-H functionalizations. Although various other strategies, such as classical approaches, enamine approaches and umpolung strategy are also known for this functionalization, here we discuss mainly the Kornblum oxidation approach and C-H functionalization strategy as they have advantages over the others. In Kornblum oxidation, the reaction uses iodine and dimethylsulfoxide and proceeds through the formation of arylglyoxal as the key intermediate. In C-H functionalization, the reaction requires metal, or metal-free catalyst, and generates radical intermediate in most cases. α-Functionalization of acetophenones is very important because of their huge applications in the synthesis of various natural products and pharmaceuticals and, therefore, a number of research articles have been published in this area. However, no review articles are available so far. In this article, we present a succinct discussion of various important and novel reactions, along with their mechanisms, published since 2012 to date. We believe that this first review article in this field will give readers one-stop information on this topic and encourage further intriguing work in this area.

L-Proline-catalyzed regioselective C1 arylation of tetrahydroisoquinolines through a multicomponent reaction under solvent-free conditions.

Here we disclose the C1 arylation of tetrahydroisoquinolines (THIQ) through regioselective C(sp3)-H functionalization using a multicomponent reaction. The reaction was performed by reacting THIQ, aldehydes and aminopyrazoles or indoles under neat conditions with l-proline as a catalyst. The regioselectivity of the products was confirmed by X-ray analysis and spectroscopic data. The formation of an azomethine ylide intermediate is crucial for obtaining the regioselectivity.

Recent Advances on the C2-Functionalization of Indole via Umpolung.

Heterocyclic compounds having a nitrogen atom in the ring exhibit very interesting biological activities. Indole is the core structure of many bioactive compounds owing to its high affinity to bind with most biological targets. Indole is an electron-rich compound and generally prefers electrophilic rather than nucleophilic substitution. Hence, many important indole derivatives are difficult to synthesize through the conventional reactivity of indole. This limitation can be avoided by using the umpolung, from the German word meaning polarity inversion. In umpolung, the indole molecule, especially the C2 and C3 positions, behave as an electrophile. As C2-functionalized indoles have substantial importance in synthetic and pharmaceutical chemistry, this review focuses on the C2 umpolung of indoles via the indirect approach which is less explored. Unlike direct approaches of indole umpolung, indirect methods have several advantages and therefore a number of research articles have been published in this field. But no review is available up till now. This is the first review on this topic and we believe that it will surely motivate the readers to work in this area further.

Multi-component synthesis of 3-substituted indoles and their cyclisation to α-carbolines via I2-promoted intramolecular C2 oxidative amination/aromatisation at room temperature.

Condensation of indoles, aldehydes and pyrazol-5-amine in the presence of ceric ammonium nitrate gives 3-substituted indoles. These then cyclise to α-carbolines at room temperature through I2-promoted intramolecular C2 amination and aromatisation in open air. A plausible mechanism is proposed based on some controlled experiments.

Introducing tetramethylurea as a new methylene precursor: a microwave-assisted RuCl3-catalyzed cross dehydrogenative coupling approach to bis(indolyl)methanes.

Herein we report a microwave assisted Ru(iii)/TBHP-mediated reaction of indoles with tetramethylurea (TMU) synthesizing symmetrical as well as unsymmetrical bis(indolyl)methanes, where TMU acts as a methylenating agent. This is the first report where TMU is used as a methylene source. Moreover, the synthesis of unsymmetrical bis(indolyl)methanes by using a carbon precursor is also reported herein for the first time. Various substituted indoles are used for the reaction. The reaction is high yielding and takes a much shorter time to accomplish compared to the existing methods.

Can a C-H···O interaction be a determinant of conformation?

Whether nonconventional hydrogen bonds, such as the C-H···O interaction, are a consequence or a determinant of conformation is a long-running and unresolved issue. Here we outline a solid-state and quantum mechanical study designed to investigate whether a C-H···O interaction can override the significant trans-planar conformational preferences of α-fluoroamide substituents. A profound change in dihedral angle from trans-planar((OCCF)) to cis-planar((OCCF)) observed on introducing an acceptor group for a C-H···O hydrogen bond is consistent with this interaction functioning as a determinant of conformation in certain systems. This testifies to the potential influence of the C-H···O hydrogen bond and is consistent with the assignment of this interaction as a contributor to overall conformation in both model and natural systems.

Synthesis, anticonvulsant activity, and neuropathic pain-attenuating activity of N-benzyl 2-amino-2-(hetero)aromatic acetamides.

N-Benzyl 2-acetamido-2-substituted acetamides, where the 2-substituent is a (hetero)aromatic moiety, are potent anticonvulsants. We report the synthesis and whole animal pharmacological evaluation of 16 analogues where the terminal 2-acetyl group was removed to give the corresponding primary amino acid derivatives (PAADs). Conversion to the PAAD structure led to a substantial drop in seizure protection in animal tests, demonstrating the importance of the N-acetyl moiety for anticonvulsant activity. However, several of the PAADs displayed notable pain-attenuating activities in a mouse model.

Sheet-forming abiotic hetero foldamers.

Abiotic hetero oligomers, adopting a well-defined extended self-assembled sheet-like structure, derived from conformationally constrained aliphatic and aromatic amino acid residues repeating at regular intervals are reported.

BINOL-based foldamers--access to oligomers with diverse structural architectures.

In this article, we report on the synthesis and conformation of a new family of aromatic oligoamide foldamers based on binaphthol (BINOL) monomers. A series of oligomers with differing chirality of the individual BINOL building blocks and mixed sequences of alternate BINOL and pyridyl building blocks has been synthesized and structurally characterized. NMR and quantum chemical calculations on the basis of ab initio MO theory were performed to obtain insight into the conformational features of these oligomers. It is shown that the combination of these inherently chiral aromatic building blocks provides a novel access to a wide variety of conformationally ordered synthetic oligomers with diverse and dazzling structural architectures distinct from those classically observed.

Enforcing periodic secondary structures in hybrid peptides: a novel hybrid foldamer containing periodic gamma-turn motifs.

This note describes the design, synthesis, and conformational studies of a novel hybrid foldamer that adopts a definite compact, three-dimensional structure determined by a combined effect of the special conformational properties of the foldamer constituents. The striking feature of this de novo designed foldamer is its ability to display periodic gamma-turn conformations stabilized by intramolecular hydrogen bonds. Conformational investigations by single-crystal X-ray studies, solution-state NMR, and ab initio MO theory at the HF/6-31G* level strongly support the prevalence of gamma-turn motifs in both the di- and tetrapeptide foldamers, which are presumably stabilized by bifurcated hydrogen bonds in the solid and solution states. The strategy disclosed herein for the construction of hybrid foldamers with periodic gamma-turn motifs has the potential to significantly augment the conformational space available for foldamer design with diverse backbone structures and conformations.

Self-assembly with degenerate prototropy.

This work describes a rational approach for addressing the prototropy-related problems in heterocycle-based self-assembling systems by the use of degenerate prototropy. As a proof of principle, the utility of degenerate prototropy is demonstrated herein by developing heterocycle-based AADD-type self-assembling modules that exist as "single set of protameric pair (duplex)" in both solution and solid states. These self-assembling modules are quickly accessible in good yield by reacting 2-amino-5,5-disubstituted-1H-pyrimidine-4,6-diones, available in one step by the condensation of alpha,alpha-dialkyl malonates and free guanidine, with isocyanates. Evidence from NMR spectroscopy, ESI mass spectrometry, and single-crystal X-ray diffraction studies confirmed the formation of molecular duplexes. The effect of electronic repulsion in duplex formation is also investigated. Their ready synthetic accessibility, remarkably high propensity to crystal formation, and the novel property of degenerate prototropy would make these novel self-assembling molecules promising candidates for many proposed applications.