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Introduction: Measurable residual disease (MRD) has been reported as a strong independent prognostic factor in AML, particularly in guiding decisions for hematopoietic cell transplantation in first remission. The recent consensus guidelines established by the European Leukemia NET (ELN) have emphasized molecular characterization and risk stratification for individuals with AML and recommended MRD by flow cytometry (FC) assessment in the evaluation of treatment response and monitoring in AML. Aim: We evaluated the impact of MRD status on clinical outcomes after initial induction therapy in pediatric patients diagnosed with AML and MRD-FC as a tool to support relapse risk classification. Material and methods: Overall, 48 bone marrow (BM) samples of 16 pediatric patients (62% F and 38% M), median age of 8,5 years – 0 to 16 years) were diagnosed with AML between 2021-2024, at a public pediatric hospital. All patients received the chemotherapy protocol GELMAI. BM samples were obtained at different time points after treatment (15 post induction I, 14 post induction II, 13 post intensification, 2 pre-transplant and 4 post-transplants). MRD-FC was performed in all samples with a panel with antibody combinations - 8 colors, according to ELN. All BM samples were studied with the acquisition of ≥1,5 × 106 events per sample. FACS Canto cytometer and Infinicyt software were used for acquisition and analysis. Risk classification considers molecular and cytogenetics findings at diagnosis and MRD status during treatment response assessment (positive MRD > 0.1% after induction II). The patients were classified according to GELMAI protocol as low-risk, intermediate risk, and high-risk. Event-free survival curves (EFS), defined as the time from diagnosis to progression and/or disease recurrence or patient death during the study. The study was approved by local ethics committee. Results: Positive MRD was detected in 42% (20/48) of BM studied, being 67% (10/15) at post induction I, 35% (5/14) at post induction II and 38% (5/13) at post intensification. In this study, 56% of patients were stratified as high-risk. Throughout the study, 3/16 patients relapsed after intensification phase and 4/16 died early (one after induction phase and one before starting treatment). Negative MRD AML patients at post-induction II had longer EFS compared to positive MRD cases and did not relapse, although the difference was not statistically significant (p = 0.06). Discussion: AML is a complex hematological neoplasm from a cytogenetic, molecular and morphological point of view. Several studies have shown MRD by flow cytometry is an important biomarker in AML being used for prognostic, predictive, monitoring, and efficacy-response assessments. MRD is a fast, sensitive method and can provide an independent prognostic factor when evaluated after post-induction therapy. We demonstrated that MRD is crucial for risk stratification and treatment planning, with MRD positivity linked to an increased risk of early relapse, though not statistically significant due to limited sample size and follow-up. Thus, further investigations with larger series of paired diagnostic and follow-up BM samples from AML patients are required. Conclusion: MRD-FC has become an indispensable tool for prognosis, clinical management, and guiding decisions, being feasible to introduce as a tool for treatment response assessment and risk stratification after post-induction.

Introdução: Neoplasias de células mastocíticas (CM) compõem um grupo heterogêneo de doenças, mas com apresentação clínica semelhante, sendo a histopatologia e biologia molecular (BM) essenciais para diagnóstico diferencial. Na Leucemia Mieloide Aguda (LMA) core binding fator, frequentemente CM estão aumentadas, sendo parte dessas leucemias secundária a Mastocitose Sistêmica (MS). Esses achados já foram relatados em adultos, mas é raro em crianças. A mutação D816V está relacionada à LMA e é o principal componente para diferenciá-la da Leucemia Mielomastocítica Aguda (LMMA). O objetivo desse trabalho foi relatar um caso de LMA com MS e com fusão RUNX1-RUNX1T1 mutação no éxon 8 do gene KIT em uma paciente pediátrica. Metodologia: Dados clínicos e laboratoriais foram obtidos por prontuário médico. A análise da medula óssea (MO) utilizou: citometria de fluxo para Imunofenotipagem (IFT) e Doença Residual Mínima (DRM), banda G para citogenética, RT-PCR para fusão gênica e sequenciamento Sanger para o gene KIT. Caso: Paciente com 6 anos, feminino, procedente da Guiana, admitida em dezembro de 2022 com história de febre e dor abdominal. A mãe é portadora de HIV, fazendo uso de retroviral durante toda a gestação, sem saber referir qual medicamento. Ao exame físico mostrava discretas petéqueas em tronco e abdome, exoftalmia à esquerda com hiperemia e edema de partes moles. Exames laboratoriais mostraram: funções renal e hepática preservadas, sorologia negativa para HIV, mas positivo para CMV, EBV e Parvovírus; foi visto ainda alterações hematológicas (Hb: 5,3 g/dL, HTC: 16,3%, Plaquetas: 16.000/mm3, Leucometria: 38.260/mm3) com 89% de blastos. A IFT da MO mostrou a presença de duas populações de células blásticas de linhagem mieloide: I- 39,1% e II- 28,7%. Além disso, foi observada a presença de 3,73% de CM. A citogenética mostrou 46,XX,der(8)t(8;21)(q22;q22)[12]/ 46,XX,t(8;21)(q22;q22)[2]/46,XX[6] e a BM evidenciou fusão RUNX1-RUNX1T1, e as mutações A) KIT :c.1249_1250insCTTTTT p.Ile416_Leu417insProPhe e B) KIT :c.2447A>T p.Asp816Val nos éxons 8 e 17 do gene KIT, respectivamente. A paciente foi diagnosticada com LMA com MS sendo tratada pelo protocolo GELMAI como alto risco. Após o primeiro MAG, a DRM mostrou 22,9% da população I e 0,67% da II, além de 22,6% de CM. A mutação B não estava presente, mas mantinha a A e a fusão RUNX1-RUNX1T1. Já após o ADE, a DRM mostrava ausência de blastos, mas 19,46% de CM e a BM se mantinha igual à avaliação anterior. A presença de CM, sem blastos, e com fusão RUNX1-RUNX1T1 se manteve até a última avaliação (dia 02.06.2023). A mutação A foi detectada até a avaliação pós ADE. A paciente foi encaminhada para transplante de medula óssea, e no momento está aguardando o procedimento. Discussão: O caso apresentado mostra um achado raro por se tratar de um paciente pediátrico. A mutação B foi essencial para diagnosticá-la como uma LMA com MS e não como LMMA. Mesmo após o desaparecimento dos blastos e da mutação B, as CM permanecem, assim como a fusão RUNX1-RUNX1T1. Isto leva a crer que a fusão está presente apenas nas CM, juntamente com a mutação A. Este é o primeiro caso relatado de uma LMA com MS, com mutação no éxon 8 do KIT em um paciente pediátrico. Conclusão: A análise de BM foi essencial para o diagnóstico. Maiores estudos são necessários para avaliar se a fusão RUNX1-RUNX1T1 estava presente apenas nas CM.

Introduction: The recent active use of immunotherapy based on CD19/CD3 bispecific T-cell engager (blinatumomab), brings significant problems on monitoring Minimal Residual Disease (MRD) based on Multiparameter Flow Cytometry (MFC), due to possible CD19 downregulation by tumor cells. This phenomenon breaks the well-established approach of MFC strategy analysis, based gating on CD19 positivity. Also, the selective pressure of the CD19-directed immunotherapy increases the incidence of the so-called lineage switch, which has become one of the possible mechanisms of BCP-ALL resistance to immunotherapy. At present, there is no consensus approach to MFC-MRD monitoring after blinatumomab therapy for BCP-ALL. There are several described changes in MRD methodology, including the addition of other early B-lineage antigens (e.g., CD22, CD24 and CD79a) or only the modification of the gating strategy using conventional sets of antibodies. Aim: Evaluated two different antibody panels to monitor MFC-MRD in patients Relapsed/Refractory (R/R) B-cell ALL after blinatumomab therapy. Materials and methods: All Bone Marrow (BM) samples the MRD detection was performed with panel EuroFlow BCPALL MRD protocol standardized and added two more tubes (8 colors) with early B-lineage antigens according to previously described in literature (e.g., Tube 1: CD66b/CD22/CD34/CD19/CD24/CD38/CD10/CD45; Tube 2: CD20/CD22/CD34/CD19/CD79a/CD38/CD10/CD45). All BM samples were studied following the EuroFlow SOPs with the acquisition at least ≥5×106 events per samples and in both panels. The cytometer FACSCanto 8-color and Infinicyt software was used for acquisition and analyzed data files. The study enrolled real-world children in public health care systems and was approved by the local ethics committees. Results: A total of 54 BM samples obtained from 11 children -48% M and 52% F with a median age of 10-years (0‒19) with R/R B-cell ALL were studied at different time points after treatment with blinatumomab, including: pré-transplant (n = 24) and post-transplant (n = 30). As controls without use of blinatumomab were include 04 BM from children with B-cell ALL at D15 of treatment with standard chemotherapy protocol. MRD were detected in 35% (19/54) of BM studied and of these 2/11 relapsed. We found 100% agreement between the two panels used. Only one sample was discordant at first time, but upon review it was noted that this CD19 negative population were very early CD19- normal B cell progenitors. Discussion: The wide implementation of CD19-directed therapy in the treatment in protocol for R/R BCP-ALL significantly complicated the rather routine procedure of MRD monitoring. Despite the subjective impressions by these investigators that other B-cell antigens such as CD22, CD24 and cyCD79a brings more confidence to analyze B-cell ALL MRD samples from patients treated with anti-CD19 therapy, for this studied cohort, we did not find difference on the results of MRD with the standard EuroFlow panel and the alternative panel. Conclusion: No difference was found on the MRD detection with the standard EUFOLOW panel and the alternative panel. Although introduction of CD22, and CD24 markers, with 8 colors strategy, it was not advantageous. Using 8 colors strategy, it may be recommended to investigate the comparative financial impact of the EuroFlow, and the alternative panel in the context of Blinatumomab therapy.

Two populations of Physalis patula Miller collected in different localities (Querétaro and Teotihuacán) of Central México were analyzed. Eight new compounds including three withanolides, physapatolides A-C (1-3), two labdanes, 12-epi-physacoztomatin (10) and physapatulone (12), besides three 12-O-glucosyl labdanes, patulosides A-C (13-15), were isolated from these collections. A series of known withanolides, flavonoids, labdanes, sucrose esters, and sterols were also isolated. Withanolides isolated of each population exhibited different substitution patterns of ring D, thus while 15,16-dioxygenated withanolides were found in the Querétaro population, oxygenation occurs at C-14 and C-15 in those isolated from Teotihuacán population. The structures of all the isolated compounds were determined by analysis of their spectroscopic and spectrometric data. The absolute configuration assigned to physapatolide A (1) was confirmed by X-ray diffraction analysis of its acetyl derivative 1a, while those of labdane diterpenoids were based on chemical correlations. The antibacterial activity of 16 of the isolated compounds (1-3, 5-9, 13, 14, and 16-21) and two derivatives (13a, 14a) was evaluated against five ATCC bacterial strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis). Compounds 1-3 inhibited around 100 % the growth of S. aureus at 250 μg/mL (w/v). The minimum inhibitory concentrations (MIC) of compounds 1, 2, and 3, against S. aureus were 62.5, 125 and 62.5 μg/mL, respectively, whereas their MIC's against a Methicillin-resistant S. aureus (MRSA) clinical isolate were 125, 62.5 and 62.5 μg/mL, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study investigated the impact of adding hydroxyapatite nanoparticles to implant surfaces treated with zirconia blasting and acid etching (ZiHa), focusing on structural changes and bone healing parameters in low-density bone sites. The topographical characterization of titanium discs with a ZiHa surface and a commercially modified zirconia-blasted and acid-etched surface (Zi) was performed using scanning electron microscopy, profilometry, and surface-free energy. For the in vivo assessment, 22 female rats were ovariectomized and kept for 90 days, after which one implant from each group was randomly placed in each tibial metaphysis of the animals. Histological and immunohistochemical analyses were performed at 14 and 28 days postoperatively (decalcified lab processing), reverse torque testing was performed at 28 days, and histometry from calcified lab processing was performed at 60 days The group ZiHa promoted changes in surface morphology, forming evenly distributed pores. For bone healing, ZiHa showed a greater reverse torque, newly formed bone area, and bone/implant contact values compared to group Zi ( p < 0.05; t -test). Qualitative histological and immunohistochemical analyses showed higher features of bone maturation for ZiHa on days 14 and 28. This preclinical study demonstrated that adding hydroxyapatite to zirconia-blasted and acid-etched surfaces enhanced peri-implant bone healing in ovariectomized rats. These findings support the potential for improving osseointegration of dental implants, especially in patients with compromised bone metabolism.

In this work, it is proposed the development of organic semiconductors (OS) based on uranyl(VI) complexes. The above by means of the synthesis and the characterization of the complexes by Infrared spectroscopy, Nuclear magnetic resonance spectroscopy, mass spectrometry, and X-ray diffraction. Films of these complexes were deposited and subsequently, topographic and structural characterization was carried out by Scanning Electron Microscopy, X-ray diffraction, and Atomic Force Microscopy. Additionally, the nanomechanical evaluation was performed to know the stiffness of uranyl films using their modulus of elasticity. Also, the optical characterization took place in the devices and their bandgap value ranges between 2.40 and 2.93 eV being the minor for the film of the uranyl complex with the N on pyridine in position 4 (2 c). Finally, the electrical behavior of the uranyl(VI) films was evaluated, and important differences were obtained: the uranyl complex with the N on pyridine in position 2 (2 a) film is not influenced by changes in lighting and its current density is in the order of 10 -3  A/cm 2 . The film with uranyl complex with the N on pyridine in position 3 (2 b) and 2 c presents a greater current flow under lighting conditions and two orders of magnitude larger than in film 2 a. In these films 2 b and 2 c, ohmic behavior occurs at low voltages, while at high voltages the charge transport changes to space-charge limited current behavior., (© 2023 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

A family of stilbenyl-azopyrroles compounds 2a-d and 3a-d was efficiently obtained via a Mizoroki-Heck C-C-type coupling reaction between 2-(4'-iodophenyl-azo)- N -methyl pyrrole (1a) and different vinyl precursors. The influence of the π-conjugated backbone and the effect of the pyrrole moiety were correlated with their optical properties. Studies via UV-Visible spectrophotometry revealed that the inclusion of EWG or EDG favors a red-shift of the main absorption band in these azo compounds compared with their non-substituted analogues. Furthermore, there is a clear influence between the half-life of the Z isomer formed by irradiation with white light and the push-pull behavior of the molecules. In several cases, the stilbenyl-azopyrroles led to the formation of J-type aggregates in binary MeOH : H 2 O solvents, which are of interest for water compatible applications.

cis -2- tert -Butyl-5-( tert -butylsulfonyl)-1,3-dioxane ( cis -1) exhibits a high degree of eclipsing in the H-C5-S-C segment in the solid state, the origin of which remains unexplained. The eclipsed conformation that corresponds to an energetic minimum in the solid state practically corresponds to a rotational transition state in solution, which allows an approach to understand transitions states. The difference in the enthalpy of sublimation Δ sub H between cis -1 and the more stable trans -1 is 8.40 kcal mol -1 , lets to consider that the intermolecular interactions in the crystalline structure must be responsible for the conformational effect observed in the solid state. The study of the experimental electron density of cis -1 in solid state allowed to establish that CH⋯OS intermolecular interaction is the main contribution to the observed eclipsing. The charge density analysis was also performed using the quantum theory of atoms in molecules to evaluate the nature and relevance of the intermolecular interactions in the crystal structure.

We have developed a straightforward and rapid methodology for the synthesis of tetrasubstituted allenes bearing carboxylic acids in the 1,3-position through the gold(I)-catalyzed nucleophilic addition of bis(trimethylsilyl)ketene acetals to ynones. The reaction was evaluated with several substrates, and 21 allenes were obtained in moderate to good yields. Using DFT calculations, we studied the mechanism of the reaction, which suggested a nucleophilic 1,4-addition pathway. The potential of allenes to act as a source of highly functionalized lactones was also explored.

We herein report the synthesis and catalytic application of a new family of dinuclear Cu(I) complexes based on [N,P]-pyrrole ligands. The Cu(I) complexes (4a-d) were obtained in good yields and their catalytic properties were evaluated in the1,3-dipolar cycloaddition of azomethine ylides and electron-deficient alkenes. The air-stable complexes 4a-d exhibited high endo-diasteroselectivity to obtain substituted pyrrolidines, and the catalytic system showed excellent reactivity and wide substitution tolerance.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC) 2 -Ga) and Dimethoxycurcumin indium ((DiMeOC) 3 -In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC) 2 -Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC) 3 -In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML 3 complex. The cytotoxic activity of the (DiMeOC) 2 -Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

From the bioactive extract of the euphorbiaceous Croton niveus Jacq., three previously unreported ent-rosane diterpenes have been isolated and characterized by conventional methods, in addition to the known compounds lupeol, cajucarinolide and some phytosterols. Two of the ent-rosane diterpenes displayed activity against HCT-15 and PC-3 cancer cell lines, and the results of docking calculations of these compounds with NF-κB and STAT3 receptors agreed with the proposed mode of action of diterpenes against PC-3 cells., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The first single crystal structure of the homoleptic copper (II) ML 2 complex (M=Cu (II), L = curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry, also confirmed by EPR. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing Crystallinity was additionally assessed by XRD patterns. The log P value of the complex (2.3 ± 0.15) was determined showing the improvement in water solubility. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines, with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

To our previously reported first crystal structure of a homoleptic zinc curcuminoid complex with square pyramidal geometry, we add herein three new geometries of homoleptic type complexes i.e. octahedral, trigonal-pyramidal, and trigonal-bipyramidal. Octahedral geometry was observed in the new pseudo-polymorph of the DAC-Zn complex resulting from crystallization in DMF, while square-pyramidal geometry was obtained in DMSO. Improving crystallinity involved suppressing the phenolic interactions by etherification and esterification. The complete characterization of these complexes was carried out using SCXRD, IR, MS, EA, liquid, and solid-state NMR. Moreover, the cytotoxic activity of all complexes was evaluated. The IC 50 values for the DiMeOC-Zn (7) complex were 8 or 22 times higher than for cisplatin in the U251 and HCT-15 cell lines, indicating a high antiproliferative and therapeutic potential., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The synthesis of a series of ferrocenylvinylketenes as stable η 4 -[Fe(CO) 3 ] complexes (3a-f) was successfully accomplished through the reaction of η 2 -[Fe(CO) 4 ] complexes under mild carbonylation conditions. The reactivity of 3a-f under thermal conditions afforded the unexpected formation of a novel family of (μ 2 ,η 3 -allyl-η 5 -oxapentadienyl)diiron pentacarbonyl complexes 5a-f proposed to be formed by a sequence metathesis-haptotropic rearrangement between the starting η 4 -vinylketene iron(0) complex 3 and a η 4 -vinylcarbene iron(0) complex trapped in situ after a reversible carbonylation process favored by the thermal conditions. An electron density distribution analysis (EDD) of 5e using high-resolution X-ray diffraction data in combination with the DFT framework was performed to understand the electronic communication between the two iron fragments.

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu ( 9 ) constitutes the first case of a "conformationally-heteroleptic" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg ( 5 ) and ThiopheneCurc-Cu ( 9 ) have a good antioxidant effect (IC 50 = 11.26 ± 1.73 and 10.30 ± 0.59 μM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

The title compound, [Fe(C 5 H 5 )(C 8 H 7 N 2 S)], was synthesized by the direct reaction of acetyl-ferrocene, thio-urea and resublimed iodine. The structure shows one mol-ecule in the asymmetric unit. The amino-thia-zole ring makes an angle of 14.53 (13)° with the ferrocenyl ring to which it is attached. In the crystal, pairs of complex mol-ecules inter-act via inter-molecular N-H⋯N hydrogen bonds, forming a cyclic dimer which then inter-acts with other dimers through C-H⋯π inter-actions., (© Anzaldo et al. 2022.)

A series of new (tricarbonyl)rhenium(I) complexes were synthesized using chiral bidentate ligands (+)/(-)-iminopyridines (L R /L S ). The reaction yielded a mixture of mononuclear Re(I) diastereoisomers, formulated as fac -[Br(CO) 3 Re ( S / R ) L ( S / R ) ]. Each single diastereoisomer was isolated and fully characterized. X-ray crystallography and circular dichroism spectra verified their enantiomeric nature. The cytotoxicity of each complex was evaluated against six cancer cell lines. The effect of the two complexes on viability, proliferation, and migration was analyzed on glioblastoma cell lines (U251 and LN229). Changes in the expression of histones, apoptotic, and key signaling proteins, as well as alterations in DNA structure, were also observed. These experiments showed that the chirality associated with both metal and ligand has a strong influence on cytotoxicity.

The synthesis of four derivatives and the single-crystal X-ray structures of six 9-trifluoromethylxanthenediols (TFXdiols) I - VI are analyzed in this work. These compounds were obtained through superacid-catalyzed condensation of dihydroxybenzenes with 1,1,1-trifluoroacetone or 2,2,2-trifluoroacetophenone. The title molecules have a convex molecular structure due to their three fused rings of the xanthene moiety. We have found that, similar to resorcinol, the configuration of the hydroxyl groups is of great relevance for the crystal packing favoring either interactions above and below their molecular plane or lateral interactions that create layers. Considering that reports of TFXdiols are very scarce, our findings contribute to a better understanding of the molecular conformation and intermolecular interactions in their crystal structures. A similar analysis was extended to a fortuitous cocrystal obtained between 9-trifluoromethyl-9-(4'-fluorophenyl)-xanthenediol and 1,4-dihydroxybenzene, showing that these structures might be used to obtain cocrystals in the future., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The cyclopropane ring-opening reaction of riolozatrione, a natural product obtained from Jatropha dioica , afforded a 2,2-disubstituted 1,3-cyclohexandione displaying an alkyl methyl ether group at position 5. The conformational analysis of this product showed a high preference for the trans -diaxial conformation in both solution and solid state. Such conformation was possible from the noncovalent intramolecular n X → π* C═O interactions (X = an element having an unshared electron pair), allowing the determination of the interaction energies. Since the n X → π* C═O interactions can be regarded as additive, the energy values ranged from 4.52 to 6.51 kcal mol -1 for each carbonyl group with a strong dependency on the interatomic distances. The rigorous analysis of the electron density in the topological theory of atoms in molecules framework clearly shows that the origin of O-C═O interactions are through the n O → π* C═O electron transfer mechanism. Such interactions are slightly weaker than a canonical hydrogen bond but seemingly stronger than a van der Waals interaction. This interaction must be considered as a stereoelectronic effect due the electronic transfer between the interacting groups, which are limited by their relative stereochemistry and can be represented by a bond-no bond interaction, causing the pyramidalization of the carbonyl, which is the charge acceptor group.

This work describes the use of C-H⋯F-C contacts in the solid-state from the stator towards the rotator to fine-tune their internal motion, by constructing a set of interactions that generate close-fitting cavities in three supramolecular rotors 1-3I . The crystal structures of these rotors, determined by synchrotron radiation experiments at different temperatures, show the presence of such C-H⋯F-C contacts between extended carbazole stators featuring fluorinated phenyl rings and the 1,4-diazabicyclo[2.2.2]octane (DABCO) rotator. According to the 2 H NMR results, using deuterated samples, and periodic density functional theory computations, the rotators experience fast angular displacements (preferentially 120° jumps) due to their low rotational activation energies ( E a = 0.8-2.0 kcal mol -1 ). The higher rotational barrier for 1 (2.0 kcal mol -1 ) is associated with a larger number of weak C-H⋯F-C contacts generated by the stators. This strategy offers the possibility to explore the correlation among weak intermolecular forces, cavity shape, and internal dynamics, which has strong implications in the design of future fine-tuned amphidynamic crystals., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Two new crystalline rotors 1 and 2 assembled through N-H⋅⋅⋅N hydrogen bonds by using halogenated carbazole as stators and 1,4-diaza[2.2.2]bicyclooctane (DABCO) as the rotator, are described. The dynamic characterization through 1 H T 1 relaxometry experiments indicate very low rotational activation barriers (E a ) of 0.67 kcal mol -1 for 1 and 0.26 kcal mol -1 for 2, indicating that DABCO can reach a THz frequency at room temperature in the latter. These E a values are supported by solid-state density functional theory computations. Interestingly, both supramolecular rotors show a phase transition between 298 and 250 K, revealed by differential scanning calorimetry and single-crystal X-ray diffraction. The subtle changes in the crystalline environment of these rotors that can alter the motion of an almost barrierless DABCO are discussed here., (© 2020 Wiley-VCH GmbH.)

Curcumin, the most important secondary metabolite isolated from Curcuma longa , is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono ( 1 ), di ( 2 ), tri ( 3 ), tetra ( 4 ) benzylated and dibenzyl-fluoroborate ( 5 ), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 μM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

A new family of push-pull biphenyl-azopyrrole compounds 3b-g and 4b-d was efficiently obtained via a Suzuki cross-coupling reaction between 2-(4'-iodophenyl-azo)-N-methyl pyrrole (1a) or 3-(4'-iodophenyl-azo)-1,2,5-trimethyl pyrrole (2a) and 4'-substituted phenyl boronic acids in excellent yields. The influence of the π-biphenyl backbone and pyrrole pattern substitution was correlated with their optical properties. Solvatochromic studies via UV-visible spectrophotometry revealed that the inclusion of a 4'-nitro-biphenyl fragment favors a red-shift of the main absorption band in these azo compounds compared with their non-substituted analogues. Likewise, optical band-gaps were estimated by means of electronic absorption spectra and correlated with TD-DFT studies. The pyrrole pattern substitution and the π-conjugated backbone exhibit a clear influence on their thermal isomerization kinetics at room temperature. In all cases, biphenylazo-pyrrole compounds lead to the formation of J-type aggregates in binary MeOH : H2O solvents. Under these conditions, compounds 3b-c undergo a water-assisted cis-to-trans isomerization at room temperature.

Both DNA barcoding and phylogenetic data of the studied botanical material suggested the existence a new population of Galphimia glauca. Their leaves afforded three new nor-3,4-seco-friedelanes named galphimines M-O, together with known galphimines D, E, G, and I. Galphimines M and N possess bicyclic orthoacetates which are the first examples of orthoesters found in the Malpighiaceae family, while galphimine O has a 27,20-δ-lactone moiety. The structures elucidation followed from spectroscopic means and the absolute configuration followed from single crystal X-ray diffraction analyses. Tests for antibacterial and antifungal activities of galphimines N and M showed no promising effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A new rotor exhibits rich solvatomorphism behavior with eight X-ray structures obtained. A heterogeneous solid obtained by mechanical stress exhibited a dominant isotropic 2 H line shape at high temperatures. The motion occurs only in the amorphous component of this solid, with an E a of 7.4 kcal mol -1 and a low pre-exponential factor A of 6.22 × 10 10 s -1 , which indicates that the motion requires the distortion of the molecular axis.

Chemical investigation of the aerial parts (except fruits and calixes) of Physalis nicandroides var. attenuata led to the isolation of a series of new labdane-type diterpenoids, including the closely related compounds 1 - 3 , the labdane glucosides 4 and 5 , a mixture of the epimeric alcohols 6 and 7 , and one labdanetriol, isolated as its tri- O -acetyl derivative 9 . In addition, three new withanolides ( 14 - 16 ) and six known compounds were isolated. The structures of these compounds were elucidated by analysis of their spectroscopic data and chemical transformations, and those of compounds 1 , 4 , and 16 were confirmed by X-ray diffraction analysis of the natural product ( 1 ) and of the corresponding acetyl derivatives 4a and 16a . Fourteen of these compounds were assayed for their in vitro inhibitory activity against yeast α-glucosidase and acetylcholinesterase enzymes. The results were negative in both cases, except for compound 3a that marginally inhibited the activity of acetylcholinesterase with an IC 50 value of 64.4 μM.

Several phthalides were semisynthesized, including a 3,8-dihydrodiligustilide with progesterone-like activity, previously isolated from Ligusticum chuanxiong , the structure of which was earlier assigned to a semisynthetic product with nonidentical spectroscopic constants. The structure of this natural phthalide was reassigned with a proposal of its absolute configuration. Phthalides acted as progestins in cell viability assays, immunofluorescence microscopy, and docking analysis. Therefore, the structures for natural and semisynthetic phthalides with potential use in hormone-related therapies were reassigned.

Nine terpenoids were isolated from the leaves and flowers of Salvia amarissima, including a new acylated diterpenoid glucoside, amarisolide F (1), a new neo-clerodane diterpenoid, amarissinin D (2), which was isolated as an acetyl derivative (2a), and four known diterpenoids. The structure of amarisolide F (1) was elucidated by NMR and MS data analyses, as well as its methanolysis products 7 and 8, which also constituted new diterpenoids, named amarissinin E and 8- epi-amarissinin E, respectively. The absolute configuration of compound 7 was established by single-crystal X-ray diffraction. The cytotoxicity and anti-MDR effect of 1 in three phenotypes of the MCF-7 cell lines were assayed. Compound 1 was 2-3.6-fold more active than amarissinins A (3) and B (4), but several orders of magnitude less active than teotihuacanin (6) and reserpine.

Herein we report two crystalline molecular rotors 1 and 4 that show extremely narrow signals in deuterium solid-state NMR spectroscopy. Although this line shape is typically associated with fast-moving molecular components, our VT 2 H NMR experiments, along with X-ray diffraction analyses and periodic DFT computations show that this spectroscopic feature can also be originated from low-frequency intramolecular rotations of the central phenylene with a cone angle of 54.7° that is attained by the cooperative motion of the entire structure that distorts the molecular axis to rotation. In contrast, two isomeric structures ( 2 and 3 ) do not show a noticeable intramolecular rotation, because their crystallographic arrays showed very restricting close contacts. Our findings clearly indicate that the multiple components and phase transitions in crystalline molecular machines can work in concert to achieve the desired motion.

We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.

A new series of Fischer carbenes have been synthetized and examined as hole-transporting or electron-transporting layers (HTLs or ETLs) in the fabrication of organic solar cells (OSCs). The synthesis of three Fischer aminocarbene complexes with the general formula [Cr(CO)₅{C(NHCH₂)Ar}] (Ar = 2-pyridyl ( 3a ), 3-pyridyl ( 3b ) and 4-pyridyl ( 3c )) is reported. The molecular structure of complex 3b has been confirmed by X-ray analysis. In order to study the possible applications of the three Fischer aminocarbenes in OSCs, thin films of these complexes were prepared using a vacuum deposition process. These organometallic films were chemically and morphologically characterized by IR spectroscopy, SEM, AFM and XRD. According to the IR and Tauc analysis, the vacuum deposition process generates thin films free of impurities with an activation energy of 4.0, 2.7 and 2.1 eV for 3a , 3b y 3c, respectively. The UV-vis spectra of the amorphous aminocarbene films show that they are practically transparent to the visible radiation of the electromagnetic spectrum. This is due to the fact that their absorption is located mainly in the ultraviolet range. Two OSCs with bulk-heterojunction configuration were manufactured in order to prove the use of the aminocarbenes as ETL o HTL. The aminocarbene [Cr(CO)₅{C(NHCH₂) 4-pyridyl}] ( 3c ) proved to be suitable as ETL with a fill factor (FF) of 0.23 and a short circuit current density ( J SC ) of 1.037 mA/cm²., Competing Interests: The authors declare no conflict of interest.

Background: All antipsychotics are associated with extrapyramidal symptoms (EPS). These can present as dysphagia, esophageal dysmotility, or aspiration, all of which may not be recognized as EPS., Case Report: A 62-year-old with schizophrenia, prescribed olanzapine 5 mg daily, presented agitated and endorsed difficulty swallowing. Speech therapy suggested her complaints were related to either reflux or dysmotility. Esophageal manometry showed her lower esophageal sphincter was not fully relaxing, and identified an esophagogastric junction outflow obstruction. Despite therapeutic dilation, oral intake remained poor. Following an increase in olanzapine, she developed EPS, her dysphagia worsened, and she was choking on food. Following a switch to aripiprazole her EPS and appetite improved, and she ceased complaining of dysphagia., Discussion: Dysphagia has been reported with first- and second-generation antipsychotics. A review of the second-generation antipsychotic literature identified case reports of dysphagia with clozapine (n = 5), risperidone (n = 5), olanzapine (n = 2), quetiapine (n = 2), aripiprazole (n = 1), and paliperidone (n = 1). Postulated mechanisms of antipsychotic-induced dysphagia include that it may be an extrapyramidal adverse reaction or related to anticholinergic effects of antipsychotics. Management of dysphagia includes discontinuing the antipsychotic, reducing the dose, dividing the dose, or switching to another antipsychotic. Complications of dysphagia include airway obstruction (eg, choking, asphyxia), aspiration pneumonia, and weight loss. Additional complications include dehydration, malnutrition, and nonadherence to oral medications., Conclusion: It is important to recognize symptoms of dysphagia and esophageal dysmotility in antipsychotic-treated patients. Intervention is necessary to prevent complications.

Eleven neo-clerodane diterpenoids (1-11) including the new analogues 1, 2, and 10, and 3',5,6,7-tetrahydroxy-4'-methoxyflavone (12) were isolated from the aerial parts of Salvia polystachya. Polystachyne G (1) and 15-epi-polystachyne G (2) were isolated as an epimeric mixture, containing a 5-hydroxyfuran-2(5H)-one unit in the side chain at C-12 of the neo-clerodane framework. Polystachyne H (10) contains a 1(10),2-diene moiety and a tertiary C-4 hydroxy group. The structures of these compounds were established by analysis of their NMR spectroscopic and MS spectrometric data. The absolute configurations of compounds 3, 4, and 10 were determined through single-crystal X-ray diffraction analysis. The antibacterial, antifungal, and phytotoxic activities of the diterpenoids were determined. In addition, the stimulatory effect of the expression of extracellular matrix components of nine of the isolates (1-8 and 11) was assayed. Compounds 1-4, 8, and 11 increased the expression of the genes codifying for type I, type III, and type V collagens and for elastin.

An efficient method to obtain chiral 1,2-disubstituted ferrocenyl ligands has been developed. The introduction of planar chirality was accomplished by using 2-thiazoline as an ortho-directing lithiation group, and moreover, these kinds of ligands possess a central chirality from the amino alcohol used in their synthesis. The X-ray analysis and DFT calculations confirmed the diastereoselectivity of ortho-lithiation and the configuration of the planar chirality. The ability of these new bidentate [N,S]-ferrocene ligands to act in Pd-catalyzed asymmetric allylic alkylation has also been demonstrated and compared with their oxazoline counterparts.

Three new diterpenes (amarissinins A-C, 1-3) containing several oxygenated functionalities were isolated from the leaves and flowers of Salvia amarissima. The structures of these compounds were established through the analysis of their NMR spectroscopy and mass spectrometry data. The structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction. Compound 2 was identified as a C-10 epimer of dugesin F (5). The cytotoxic activity of these compounds against five human cancer cell lines was determined. Additionally, the capability to modulate the multidrug resistance (MDR) in the MCF-7 cancer cell line resistant to vinblastine was tested., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Arenediazonium salts generated in situ from anilines have been found for the first time to efficiently oxidize [AuCl(L)] (L = SMe2, PPh3) complexes in DMSO as a solvent, under thermal conditions. The structure of the [AuArCl2(L)] complexes formed has been confirmed by X-ray diffraction analyses. These complexes have been used as intermediates, in a one pot cross-coupling reaction of anilines with silver acetylides.

Eight cadinane-type sesquiterpenoids (1-8) together with some triterpenoids, flavonoids, and sterols were isolated from the aerial parts of Heterotheca inuloides. The structures of the new compounds (1-4) were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis. The structures of the new (1-3) and the known (5-7) sesquiterpenoids were confirmed by X-ray crystallography. The absolute configurations of metabolites 2-5 were determined by comparing their experimental and calculated electronic circular dichroism spectra and confirmed via refinement of the Flack parameter using anomalous X-ray scattering from the oxygen atoms and chemical correlation methods. The sesquiterpenoids were evaluated for their anti-inflammatory potential by applying the TPA-induced mouse ear edema model. The results revealed that some of these metabolites exhibit moderate anti-inflammatory activity. At a dose of 228 μg/ear compound 1 showed 43.14 ± 8.09% inhibition on ear edema, indicating an IC50 > 228 μg/ear.

In the crystals of the title N-halo-methyl-ated quaternary ammonium salts, C19H23IN(+)·I(-), (I) [systematic name: N-(4,4-di-phenyl-but-3-en-1-yl)-N-iodo-methyl-N,N-di-methyl-ammonium iodide], C20H25IN(+)·I(-), (II) [systematic name: N-(5,5-di-phenyl-pent-4-en-1-yl)-N-iodo-methyl-N,N-di-methyl-ammonium iodide], and C21H27IN(+)·I(-), (III) [systematic name: N-(6,6-di-phenyl-hex-5-en-1-yl)-N-iodo-methyl-N,N-di-methyl-ammonium iodide], there are short I⋯I(-) inter-actions of 3.564 (4), 3.506 (1) and 3.557 (1) Å for compounds (I), (II) and (III), respectively. Compound (I) crystallizes in the Sohncke group P21 as an 'enanti-opure' compound and is therefore a potential material for NLO properties. In the crystal of compound (I), mol-ecules are linked by C-H⋯I(-) and C-H⋯π inter-actions which, together with the I⋯I(-) inter-actions, lead to the formation of ribbons along [100]. In (II), there are only C-H⋯I(-) inter-actions which, together with the I⋯I(-) inter-actions, lead to the formation of helices along [010]. In (III), apart from the I⋯I(-) inter-actions, there are no significant inter-molecular inter-actions present.

The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) hybridized N atom, cannot be substituted by any other ligand. In contrast, the isomerized derivative [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(MeCN)2]PF6 (2), in which one MeCN ligand is now trans to the C atom of the phenyl ring orthometalated to Ru, leads to fast and quantitative substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(PPh3)(MeCN)]PF6 (3), in which PPh3 is trans to the C σ bound to Ru. Compound 3 is not kinetically stable, because, under thermodynamic control, it leads to 4, in which the PPh3 is trans to a N atom of the Phen ligand. Dimethylsulfoxide (DMSO) can also substitute a MeCN ligand in 2, leading to 5, in which DMSO is coordinated to Ru via its S atom trans to the N atom of the Phen ligand, the isomer under thermodynamic control being the only compound observed. We also found evidence for the fast to very fast substitution of MeCN in 2 by water or a chloride anion by studying the electronic spectra of 2 in the presence of water or NBu4Cl, respectively. An isomerization related to that observed between 3 and 4 is also found for the known monophosphine derivative [Ru(2-C6H4-2'-Py-κC,N)(PPh3, trans-C)(MeCN)3]PF6 (10), in which the PPh3 is located trans to the C of the cyclometalated 2-phenylpyridine, since, upon treatment by refluxing MeCN, it leads to its isomer 11, [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(MeCN)3]PF6. Further substitutions are also observed on 11, whereby N^N chelates (N^N = 2,2'-bipyridine and phenanthroline) substitute two MeCN ligands, affording [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(N^N)(MeCN)]PF6 (12a and 12b). Altogether, the behavior of the obtained complexes by ligand substitution reactions can be rationalized by an antisymbiotic effect on the Ru center, trans to the C atom of the cyclometalated unit, leading to compounds having the least nucleophilic ligand trans to C whenever an isomerization, involving either a monodentate or a bidentate ligand, is possible.

Teotihuacanin (1), an unusual rearranged clerodane diterpene with a new carbon skeleton containing a spiro-10/6 bicyclic system, was isolated from the leaves and flowers of Salvia amarissima. Its structure was determined through spectroscopic analyses. Its absolute configuration was established by single-crystal X-ray diffraction. Compound 1 showed potent modulatory activity of multidrug resistance in vinblastine-resistant MCF-7 cancer cell line (reversal fold, RFMCF-7/Vin+ > 10703) at 25 μg/mL.

In the title compound, [Cu2(OH)2(C12H8N2)2(H2O)2](C12H6O4)·6H2O, the two hydroxide groups bridge the two Cu(II) cations, forming a centrosymmetric binuclear complex cation, in which the Cu(II) cation is coordinated by a 1,10-phenanthroline (phen) mol-ecule, one water mol-ecule and two bridging hydroxide O atoms in a distorted N2O3 square-pyramidal coordination geometry. The naphthalene-2,6-di-carboxyl-ate anion is also located on an inversion centre. In the crystal, O-H⋯O hydrogen bonds link the cations, anions and lattice water mol-ecules into a three-dimensional supra-molecular architecture. Extensive π-π stacking is observed between the parallel or nearly parallel aromatic rings of adjacent phen ligands and naphthalenedi-carboxyl-ate anions, the centroid-to-centroid distances ranging from 3.4990 (16) to 3.8895 (16) Å.

An efficient and practical methodology for the synthesis of 3-substituted 4H-quinolizin-4-ones using (η(4)-vinylketene)-Fe(CO)3 complexes as key intermediates has been developed. The advantage of this transformation lies in the use of simple and readily available starting materials and mild carbonylation conditions. The fluorescent properties of these compounds were determined and the quantum yield was obtained, ranging from 0.04 to 0.36 depending on the substituent.

We developed a biological sulphide oxidation system and evaluated two reactors (shaped similar to the settler compartment of an up-flow anaerobic sludge blanket [UASB] reactor) with different support materials for biomass retention: polypropylene rings and polyurethane foam. The start-up reaction was achieved using microorganisms naturally occurring on the open surface of UASB reactors treating domestic wastewater. Sulphide removal efficiencies of 65% and 90% were achieved with hydraulic retention times (HRTs) of 24 and 12 h, respectively, in both reactors. However, a higher amount of elemental sulphur was formed and accumulated in the biomass from reactor 1 (20 mg S(0) g(-1) VTS) than in that from reactor 2 (2.9 mg S(0) g(-1) VTS) with an HRT of 24 h. Denaturing gradient gel electrophoresis (DGGE) results revealed that the the pink and green biomass that developed in both reactors comprised a diverse bacterial community and had sequences related to phototrophic green and purple-sulphur bacteria such as Chlorobium sp., Chloronema giganteum, and Chromatiaceae. DGGE band patterns also demonstrated that bacterial community was dynamic over time within the same reactor and that different support materials selected for distinct bacterial communities. Taken together, these results indicated that sulphide concentrations of 1-6 mg L(-1) could be efficiently removed from the effluent of a pilot-scale UASB reactor in two sulphide biological oxidation reactors at HRTs of 12 and 24 h, showing the potential for sulphur recovery from anaerobically treated domestic wastewater.

Two new 5,10-seco-neo-clerodanes, salvimicrophyllins A and B (1 and 2), and two new neo-clerodanes, salvimicrophyllins C and D (3 and 4), were isolated from the leaves and flowers of Salvia microphylla. The structures of these compounds were elucidated mainly by analysis of their NMR spectroscopic and mass spectrometric data. The relative configurations of the salvimicrophyllins were determined by analysis of NOESY spectra and ECD curves, and the relative configuration of compound 2 was confirmed by single-crystal X-ray diffraction crystallography.

The guaianolide 8-epi-mikanokryptin (1) and the melampolide 11Hβ-11,13-dihydromicrantholide (2) along with known sesquiterpene lactones (3-13) and other constituents were isolated from the aerial parts of different populations of Mikania micrantha and Mikania cordifolia collected in several states of Mexico. The relative and absolute configurations of 1 were determined by X-ray diffraction and CD analysis, respectively. Considering the (1)H and (13)C NMR chemical shift similarities and the H-H coupling constant values, a [(1)D(14), (15)D5] conformation was established for micrantholides (2, 8-13). We tested nearly all the sesquiterpene lactones for antiproliferative activity in human cancer cell lines, and they exhibited moderate activity. Additionally, in a mouse ear model of edema induced by TPA, the anti-inflammatory activities were marginal., (Copyright © 2014 Elsevier B.V. All rights reserved.)

New 1,2-disubstituted ferrocenes [5(b-j), in which R = -SMe, -SPh, -SiPr, -SiMe3, -SePh, -SnBu3, -B(OH)2, -Me, -I] with a thiazoline ring in the ferrocene backbone using as key intermediate a ferrocenyl Fischer carbene complex were synthesized. The capability of the 2-thiazoline moiety as an ortho-directed metalation group was demonstrated by subsequent quenching of lithium intermediate with several electrophiles, proving to be an excellent method for synthesizing bidentate ligands. The catalytic scope of the [N,S] ligand 5b as the corresponding palladium complex 5b-PdCl(2) in a microwave-promoted Heck reaction was also tested. Results obtained showed better catalytic activity of 5b-PdCl(2) compared to other catalytic systems based on a [N,S] ferrocenyl ligand.