The physical nature of the noncovalent interactions involved in anion recognition was investigated in the context of metalated calix[4]arene hosts, employing Kohn−Sham molecular orbital (KS-MO) theory, in conjunction with a canonical energy decomposition analysis, at the dispersion-corrected DFT level of theory. Computed data evidence that the most stable host−guest bonding occurs in ruthenium complexed hosts, followed by technetium and molybdenum metalated macrocyclic receptors. Furthermore, the guest's steric fit in the host scaffold is a selective and crucial criterion to the anion recognition. Our analyses reveal that coordinated charged metals provide a larger electrostatic stabilization to anion recognition, shifting the calixarenes cavity toward an electron deficient acidic character. This study contributes to the design and development of new organometallic macrocyclic hosts with increased anion recognition specificity.

We have quantum chemically analyzed the bonding mechanism behind the affinity of various heterocalixarenes for anions with a range of geometries and net charges, using modern dispersion-corrected density functional theory (DFT-D3BJ). The purpose is to better understand the physical factors that are responsible for the computed affinities and thus to develop principles for a more rational design of anion receptors. Our model systems comprise heterocalixarenes 1-4 as hosts, which are characterized by different bridging heteroatoms (O, N, S) as well as the anionic guests Cl, Br, I, BF, CHCO, HPO, HSO, NCS, NO, PF, and SO. We use various analysis schemes (EDA, NCI, and NBO) to elucidate the interactions between the calixarene cavity and the anions to probe the importance of the different bonding modes (anion-π, lone-pair electron-π, σ-complexes, hydrogen bonds, and others) of the interactions. Electrostatic interactions appear to be dominant for heterocalixarenes with oxygen bridges whereas orbital interactions prevail in the case of nitrogen and sulfur bridges. Dispersion interactions are however in all cases non-negligible.

The efficacy of Licochalcone A (LicoA) and its two analogs were reported against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum in vitro, and in experimental model of L. (L.) infantum in vitro. Initially, LicoA and its analogs were screened against promastigote forms of L. (L.) amazonensis. LicoA was the most active compound, with IC50 values of 20.26 and 3.88 μM at 24 and 48 h, respectively. Against amastigote forms, the IC50 value of LicoA was 36.84 μM at 48 h. In the next step, the effectivity of LicoA was evaluated in vitro against promastigote and amastigote forms of L. (L.) infantum. Results demonstrated that LicoA exhibited leishmanicidal activity in vitro against promastigote forms with IC50 values of 41.10 and 12.47 μM at 24 and 48 h, respectively; against amastigote forms the IC50 value was 29.58 μM at 48 h. Assessment of cytotoxicity demonstrated that LicoA exhibited moderate mammalian cytotoxicity against peritoneal murine macrophages; the CC50 value was 123.21 μM at 48 h and showed about 30% of hemolytic activity at concentration of 400 μM. L. (L.) infantum-infected hamsters and treated with LicoA at 50 mg/kg for eight consecutive days was able to significantly reduce the parasite burden in both liver and spleen in 43.67 and 39.81%, respectively, when compared with negative control group. These findings suggest that chalcone-type flavonoids can be a promising class of natural products to be considered in the search of new, safe, and effective compounds capable to treat canine visceral leishmaniosis (CVL).

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Copaifera species (Fabaceae) comprises approximately 70 species of large trees, from which 16 can be found in Brazil. The oleoresins obtained from their trunk are widely used in Brazilian folk medicine, which display important antitumoral potential. Chemically, these oleoresins are mainly composed of a mixture of sesquiterpenes and diterpenes. In this paper we are describing the isolation and identification of 12 already known terpenes from oleoresins obtained from three different Copaifera species (C. multijuga, C. pubiflora and C. trapezifolia) and 2 novel diterpenes (ent-16-hidroxy-3,13 clerodadien-15,18-dioic acid and ent-labda-5,13-dien-15-oic acid) from C. trapezifolia. Both new compounds were identified by nuclear magnetic resonance (NMR) spectroscopic (1 H and 13 C NMR, correlation 1 H-1 H (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)) and by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) analyses. The cytotoxic potential of these oleoresins, their main non-volatile compounds and their volatile compound fractions were evaluated against a panel of tumoral (MCF-7, ACP01, A549, HeLa) and normal cell lines (MCF-10A, GM07492-A) through XTT (tetrazolium salt) and SRB (sulforhodamine B) assays. The novel diterpene ent-labda-5,13-dien-15-oic acid displayed relevant cytotoxic effect against most of the cancer cell lines with mean inhibitory concentration (IC 50) values ranging from 3.57 ± 1.12 to 22.56 ± 1.03 µg mL-1 , and a high selectivity level in both assays.

Brazilian green and red propolis stand out as commercial products for different medical applications. In this article, we report the antimicrobial activities of the hydroalcoholic extracts of green (EGP) and red (ERP) propolis, as well as guttiferone E plus xanthochymol (8) and oblongifolin B (9) from red propolis, against multidrug‐resistant bacteria (MDRB). We undertook the minimal inhibitory (MIC) and bactericidal (MBC) concentrations, inhibition of biofilm formation (MICB50), catalase, coagulase, DNase, lipase, and hemolysin assays, along with molecular docking simulations. ERP was more effective by displaying MIC and MBC values <100 μg mL−1. Compounds 8 and 9 displayed the lowest MIC values (0.98 to 31.25 μg mL−1) against all tested Gram‐positive MDRB. They also inhibited the biofilm formation of S. aureus (ATCC 43300 and clinical isolate) and S. epidermidis (ATCC 14990 and clinical isolate), with MICB50 values between 1.56 and 6.25 μg mL−1. The molecular docking results indicated that 8 and 9 might interact with the catalase's amino acids. Compounds 8 and 9 have great antimicrobial potential.

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Rationale Although monoketone curcuminoids (MKCs) have been largely investigated due to their biological activities, data on the gas‐phase fragmentation reactions of protonated MKCs under collision‐induced dissociation (CID) conditions are still scarce. Here, we combined electrospray ionization tandem mass spectrometry (ESI‐MS/MS) data, multiple‐stage mass spectrometry (MSn), deuterium exchange experiments, accurate‐mass data, and thermochemical data estimated by computational chemistry to elucidate and to rationalize the fragmentation pathways of eleven synthetic MKCs. Methods The MKCs were synthesized by Claisen‐Schmidt condensation under basic (1–9) or acidic (10–11) conditions. ESI‐CID‐MS/MS analyses and deuterium‐exchange experiments were carried out on a triple quadrupole mass spectrometer. MSn analyses on an ion trap mass spectrometer helped to elucidate the fragmentation pathways. Accurate‐mass data and thermochemical data, obtained at the B3LYP/6–31+G(d,p) level of theory, were used to support the ion structures. Results The most intense product ions were the benzyl ions ([C7H2R1R2R3R4R5]+) and the acylium ions ([M + H − C8H3R1R2R3R4R5]+), which originated directly from the precursor ion as a result of two competitive hydrogen rearrangements. Product ions [M + H – H2O]+ and [M + H − C6HR1R2R3R4R5]+, which are formed after Nazarov cyclization, were also common to all the analyzed compounds. In addition, •Br and •Cl eliminations were diagnostic for the presence of these halogen atoms at the aromatic ring, whereas •CH3 eliminations were useful to identify the methyl and methoxy groups attached to this same ring. Nazarov cyclization in the gas phase occurred for all the investigated MKCs and did not depend on the presence of the hydroxyl group at the aromatic ring. However, the presence and the position of a hydroxyl group at the aromatic rings played a key role in the Nazarov cyclization mechanism. Conclusions Our results reinforce some aspects of the fragmentation pathways previously published for 1,5‐bis‐(2‐methoxyphenyl)‐1,4‐pentadien‐3‐one and 1,5‐bis‐(2‐hydroxyphenyl)‐1,4‐pentadien‐3‐one. The alternative fragmentation mechanism proposed herein can explain the fragmentation of a wider diversity of monoketone curcuminoids.