Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 µM; α-Glu: 248.3 µM) with IC5O value of 6.2-23.6 µM toward α-Amy and 39.8-124.6 µM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs.

On-surface polymerization of functional organic molecules has been recently recognized as a promising route to persistent low-dimensional structures with tailorable properties. In this contribution, using the coarse-grained Monte Carlo simulation method, we study the initial stage of the Ullmann coupling of doubly halogenated chrysene isomers adsorbed on a catalytically active (111) crystalline surface. To that end, we focus on the formation of labile metal-organic precursor structures preceding the covalent bonding of chrysene monomers. Four monomeric chrysene units with differently distributed halogen substituents were probed in the simulations, and the resulting precursor structures were compared and quantified. Moreover, the effect of (pro)chirality of chrysene tectons on the structure formation was elucidated by running separate simulations in enantiopure and racemic systems. The calculations showed that suitable manipulation of the halogen substitution pattern allows for the creation of diverse precursor architectures, ranging from straight and winded chains to cyclic oligomers with enantiopure, racemic, and nonracemic composition. The obtained findings can be helpful in developing synthetic strategies for covalent polymers with predefined architecture and functionality.

We report on-surface synthesis of heterochiral 1D heptahelicene oligomers after deposition of a racemic heptahelicene monomer on an Au(111) surface followed by Ullmann coupling under ultrahigh vacuum conditions. Structure, chirality and mode of adsorption of the resulting dimers to octamers are inferred from the scanning probe microscopy and theoretical calculations.

Bipyridine and related compounds are starting materials or precursors for a variety of valuable substances such as biologically active molecules, ligands for catalysts, photosensitizers, viologens, and supramolecular architectures. Thus, it is important to classify their synthesis methods and understand their characteristics. Representative examples include methods using homo and heterocoupling of pyridine derivatives in the presence of a catalyst. Because bipyridine compounds strongly coordinate with metal centers, a decrease in catalytic activity and yield is often observed in the reaction system. To address this issue, this review provides insights into advances over the last ~30 years in bipyridine synthesis using metal complexes under both homogeneous and heterogeneous conditions. Moreover, strategies for bipyridine synthesis involving sulfur and phosphorous compounds are examined. These alternative pathways offer promising avenues for overcoming the challenges associated with traditional catalysis methods, providing a more comprehensive understanding of the synthesis landscape.

The bottom-up synthesis of carbon-based nanomaterials directly on semiconductor surfaces allows for the decoupling of their electronic and magnetic properties from the substrates. However, the typically reduced reactivity of such nonmetallic surfaces adversely affects the course of these reactions. Here, we achieve a high polymerization yield of halogenated polyphenyl molecular building blocks on the semiconducting TiO2(110) surface via concomitant surface decoration with cobalt atoms, which catalyze the Ullmann coupling reaction. Specifically, cobalt atoms trigger the debromination of 4,4″-dibromo-p-terphenyl molecules on TiO2(110) and mediate the formation of an intermediate organometallic phase already at room temperature (RT). As the debromination temperature is drastically reduced, homocoupling and polymerization readily proceed, preventing presursor desorption from the substrate and entailing a drastic increase of the poly-para-phenylene polymerization yield. The general efficacy of this mechanism is shown with an iodinated terphenyl derivative, which exhibits similar dehalogenation and reaction yield.

We report on the development of a novel class of diaryl ether herbicides. After the discovery of a phenoxybenzoic acid with modest herbicidal activity, optimization led to several molecules with improved control of broadleaf and grass weeds. To facilitate this process, we first employed a three-step combinatorial approach, then pivoted to a one-step Ullmann-type coupling that provided faster access to new analogs. After determining that the primary target site of our benchmark diaryl ethers was acetolactate synthase (ALS), we further leveraged this copper-catalyzed methodology to conduct a scaffold hopping campaign in the hope of uncovering an additional mode of action with fewer documented cases of resistance. Our comprehensive and systematic investigation revealed that while the herbicidal activity of this area seems to be exclusively linked to ALS inhibition, our molecules represent a structurally distinct class of Group 2 herbicides. The structure-activity relationships that led us to this conclusion are described herein.

The diversity of surface-confined metal-organic precursor structures, which recently have been observed experimentally, poses a question of how the individual properties of a molecular building block determine those of the resulting superstructure. To answer this question, we use the Monte Carlo simulation technique to model the self-assembly of metal-organic precursors that precede the covalent polymerization of halogenated PAH isomers. For this purpose, a few representative examples of low-dimensional constructs were studied, and their basic structural features were quantified using such descriptors as the orientational order parameter, radial distribution function, and one- and two-dimensional structure factors. The obtained results demonstrated that the morphology of the precursor (and thus the subsequent polymer) could be effectively tuned by a suitable choice of molecular parameters, including size, shape, and intramolecular distribution of halogen substituents. Moreover, our theoretical investigations showed the effect of the main structural features of the precursors on the related indirect characteristics of these constructs. The results reported herein can be helpful in the custom designing and characterization of low-dimensional polymers with adjustable properties.

To extend the antiviral properties of 2- and 3-fluoro-3-deazaneplanocins into the evolving 3-deaza-1\',6\'-isoneplanocin library, 2- (11) and 3-fluoro-1\',6\'-iso-3-deazaneplanocin A (12) have been explored. The requisite synthesis began with an Ullmann reaction by coupling of a protected cyclopentenyl iodide with either 2-fluoro- or 3-fluoro-3-deazaadenine. Target 12 displayed significant activity towards 5 viruses (μM): H1N1 (EC50 < 0.36, CC50 > 357, SI > 1000), hepatitis B virus (EC50 1.28, CC50 > 357, SI > 279), norovirus (EC50 0.64, CC50 > 357, SI > 558), Ebola (EC50 < 0.1, CC50 > 100, SI > 1000), and Marburg (EC50 < 0.1, CC50 > 100, SI > 1000). On the other hand, while 11 showed limited antiviral effects, its toxicity was significant, precluding any further usefulness.

DNA-encoded library (DEL) recently has witnessed the swift development which has led to the new chemical entities identified for a wealthy biological interesting target; several small molecular inhibitors have moved into the late-stage clinical development. The success of DEL is heavily dependent on the chemical space which was assembled by the on-DNA chemical reactions. On-DNA C-N cross-coupling has great value for expanding the chemical space of DEL as amines are most abundant organic reagents available. Here we described the first on-DNA C-N cross-coupling reactions promoted by both Pd and Cu.

We report herein the synthesis of siloxane-functionalized CBP molecules (4,4\'-bis(carbazole)-1,1\'-biphenyl) for liquid optoelectronic applications. The room-temperature liquid state is obtained through a convenient functionalization of the molecules with heptamethyltrisiloxane chains via hydrosilylation of alkenyl spacers. The synthesis comprises screening of metal-catalyzed methodologies to introduce alkenyl linkers into carbazoles (Stille and Suzuki Miyaura cross-couplings), incorporate the alkenylcarbazoles to dihalobiphenyls (Ullmann coupling), and finally introduce the siloxane chains. The used conditions allowed the synthesis of the target compounds, despite the high reactivity of the alkenyl moieties bound to π-conjugated systems toward undesired side reactions such as polymerization, isomerization, and hydrogenation. The features of these solvent-free liquid CBP derivatives make them potentially interesting for fluidic optoelectronic applications.