Metal-organic frameworks as chemical nanoreactors for the preparation of catalytically active metal compounds.

Since the emergence of metal-organic frameworks (MOFs), a myriad of thrilling properties and applications, in a wide range of fields, have been reported for these materials, which mainly arise from their porous nature and rich host-guest chemistry. However, other important features of MOFs that offer great potential rewards have been only barely explored. For instance, despite the fact that MOFs are suitable candidates to be used as chemical nanoreactors for the preparation, stabilization and characterization of unique functional species, that would be hardly accessible outside the functional constrained space offered by MOF channels, only very few examples have been reported so far. In particular, we outline in this feature recent advances in the use of highly robust and crystalline oxamato- and oxamidato-based MOFs as reactors for the in situ preparation of well-defined catalytically active single atom catalysts (SACS), subnanometer metal nanoclusters (SNMCs) and supramolecular coordination complexes (SCCs). The robustness of selected MOFs permits the post-synthetic (PS) in situ preparation of the desired catalytically active metal species, which can be characterised by single-crystal X-ray diffraction (SC-XRD) taking advantage of its high crystallinity. The strategy highlighted here permits the always challenging large-scale preparation of stable and well-defined SACs, SNMCs and SCCs, exhibiting outstanding catalytic activities.

Managing the Redox Potential of PCET in Grotthuss-Type Proton Wires.

Expanding proton-coupled electron transfer to multiproton translocations (MPCET) provides a bioinspired mechanism to transport protons away from the redox site. This expansion has been accomplished by separating the initial phenolic proton donor from the pyridine-based terminal proton acceptor by a Grotthuss-type proton wire made up of concatenated benzimidazoles that form a hydrogen-bonded network. However, it was found that the midpoint potential of the phenol oxidation that launched the Grotthuss-type proton translocations is a function of the number of benzimidazoles in the hydrogen-bonded network; it becomes less positive (i.e., a weaker oxidant) as the number of bridging benzimidazoles increases. Herein, we report a strategy to maintain the high redox potential necessary for oxidative processes relevant to artificial photosynthesis, e.g., water oxidation and long-range MPCET processes for managing protons. The integrated structural and functional roles of the benzimidazole-based bridge provide sites for substitution of the benzimidazoles with electron-withdrawing groups (e.g., trifluoromethyl groups). Such substitution increases the midpoint potential of the phenoxyl radical/phenol couple so that proton translocations over ∼11 Å become thermodynamically comparable to that of an unsubstituted system where one proton is transferred over ∼2.5 Å. The extended, substituted system maintains the hydrogen-bonded network; infrared spectroelectrochemistry confirms reversible proton translocations from the phenol to the pyridyl terminal proton acceptor upon oxidation and reduction. Theory supports the change in driving force with added electron-withdrawing groups and provides insight into the role of electron density and electrostatic potential in MPCET processes associated with these Grotthuss-type proton translocations.

Concerted Electron-Nuclear Motion in Proton-Coupled Electron Transfer-Driven Grotthuss-Type Proton Translocation.

Photoinduced proton-coupled electron transfer and long-range two-proton transport via a Grotthuss-type mechanism are investigated in a biomimetic construct. The ultrafast, nonequilibrium dynamics are assessed via two-dimensional electronic vibrational spectroscopy, in concert with electrochemical and computational techniques. A low-frequency mode is identified experimentally and found to promote double proton and electron transfer, supported by recent theoretical simulations of a similar but abbreviated (non-photoactive) system. Excitation frequency peak evolution and center line slope dynamics show direct evidence of strongly coupled nuclear and electronic degrees of freedom, from which we can conclude that the double proton and electron transfer processes are concerted (up to an uncertainty of 24 fs). The nonequilibrium pathway from the photoexcited Franck-Condon region to the E2PT state is characterized by an ∼110 fs time scale. This study and the tools presented herein constitute a new window into hot charge transfer processes involving an electron and multiple protons.

Genetic architecture and genomic predictive ability of apple quantitative traits across environments.

Implementation of genomic tools is desirable to increase the efficiency of apple breeding. Recently, the multi-environment apple reference population (apple REFPOP) proved useful for rediscovering loci, estimating genomic predictive ability, and studying genotype by environment interactions (G × E). So far, only two phenological traits were investigated using the apple REFPOP, although the population may be valuable when dissecting genetic architecture and reporting predictive abilities for additional key traits in apple breeding. Here we show contrasting genetic architecture and genomic predictive abilities for 30 quantitative traits across up to six European locations using the apple REFPOP. A total of 59 stable and 277 location-specific associations were found using GWAS, 69.2% of which are novel when compared with 41 reviewed publications. Average genomic predictive abilities of 0.18-0.88 were estimated using main-effect univariate, main-effect multivariate, multi-environment univariate, and multi-environment multivariate models. The G × E accounted for up to 24% of the phenotypic variability. This most comprehensive genomic study in apple in terms of trait-environment combinations provided knowledge of trait biology and prediction models that can be readily applied for marker-assisted or genomic selection, thus facilitating increased breeding efficiency.

Design, Synthesis, and in†vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2-5.4 µM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.

Metabolomic Characterization of Commercial, Old, and Red-Fleshed Apple Varieties.

In this study, a metabolomic investigation was presented to correlate single polyphenolic compounds in apple pulp with quality characteristics such as antioxidant activity and content of phenolic compounds and anthocyanins in apple skin. Since the concentration of these compounds is influenced by environmental factors, the twenty-two apple cultivars originate from the same site. The polyphenolic compounds were analyzed by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). The antioxidant activity, phenolic content, and anthocyanins were evaluated on the sunny and the shady sides of apple skin by spectrometric assays. In old apple varieties, the measured parameters were higher than in the commercial and red-fleshed varieties. By contrast, the profile of flavan-3-ols and anthocyanins was variable amongst commercial and red-fleshed varieties. The partial least square (PLS) method was applied to investigate the association between the skin proprieties and the metabolic profile of the pulp. The highest coefficients of determination in prediction (Q2) were obtained for compounds quantified in old cultivars. These results provided information to define the old apple varieties as a reliable group based on the pathway of the antioxidant compounds and anthocyanins content. Our results show the possibility to find cultivars with promising health features based on their content of polyphenols suitable for commercialization or breeding.

Respuesta inmunológica a varias proteínas del H. pylori en pacientes guatemaltecos / Inmune response to various H. pylori proteins in Guatemalan patients

Se determinó la respuesta inmunológica a proteínas recombinantes de Helicobacter pylori en pacientes dis-pépticos (adultos y niños), pacientes con cáncer gástrico y sus familiares asintomáticos adultos viviendo con ellos. Se utilizó la prueba recomLine® Helicobacter IgG e IgA, y con base en el reconocimiento de los factores de virulencia VacA y CagA se determinó si la cepa de H. pylori era de tipo I o II. El análisis de los datos fue descriptivo y analítico y se estimaron los intervalos de confianza de 95%, con un nivel de error de 0.05 y Odds ratio. El 58.7% (121/206) de los pacientes presentó la bacteria en tinción histológica de biopsia, positividad que disminuyó con la edad y daño histológico. La frecuencia de la respuesta a los anticuerpos IgG fue mayor que IgA, en ambos casos ésta fue menor en los niños. Las proteínas del H. pylori más reconocidas tanto por IgA como IgG fueron VacA y CagA, y la respuesta a las otras proteínas investigadas fue mayor al aumentar el daño histológi-co. La cepa tipo I fue la que predominó en la población en estudio con 66% (136/206). Se deben continuar con los estudios de prevalencia de la cepa tipo I del H. pylori y del reconocimiento de sus antígenos en la población guatemalteca a fin de determinar su utilidad en el diagnóstico y pronóstico de la infección.

The immune response to recombinant Helicobacter pylori proteins was determined in dyspeptic patients (adults and children), patients with gastric cancer and their asymptomatic adults' relatives living with them. The recomLine® Helicobacter IgG and IgA test was used and based on the recognition of the virulence factors VacA and CagA, it was determined whether the H. pylori strain was type I or II. The data analysis was descriptive and analytic, and 95% confidence intervals were estimated, with an error level of 0.05, and Odds ratio. The patients that presented the bacterium in histological biopsy were 58.7% (121/206), positivity that decreased with age and histological damage. The frecuency of response to IgG antibodies was higher than IgA, in both cases it was lower in children. VacA and CagA were the H. pylori proteins most recognized by both IgA and IgG and it was observed that the number of recognized proteins was greater with increasing histological damage. The type I strain was the one that predominated in the study population 66% (136/206). Prevalence studies of the type I strain of H. pylori ant the recognition of its antigens in the Guatemalan population should continue in order to determine its usefulness in the diagnosis and prognosis of infection.

The apple REFPOP-a reference population for genomics-assisted breeding in apple.

Breeding of apple is a long-term and costly process due to the time and space requirements for screening selection candidates. Genomics-assisted breeding utilizes genomic and phenotypic information to increase the selection efficiency in breeding programs, and measurements of phenotypes in different environments can facilitate the application of the approach under various climatic conditions. Here we present an apple reference population: the apple REFPOP, a large collection formed of 534 genotypes planted in six European countries, as a unique tool to accelerate apple breeding. The population consisted of 269 accessions and 265 progeny from 27 parental combinations, representing the diversity in cultivated apple and current European breeding material, respectively. A high-density genome-wide dataset of 303,239 SNPs was produced as a combined output of two SNP arrays of different densities using marker imputation with an imputation accuracy of 0.95. Based on the genotypic data, linkage disequilibrium was low and population structure was weak. Two well-studied phenological traits of horticultural importance were measured. We found marker-trait associations in several previously identified genomic regions and maximum predictive abilities of 0.57 and 0.75 for floral emergence and harvest date, respectively. With decreasing SNP density, the detection of significant marker-trait associations varied depending on trait architecture. Regardless of the trait, 10,000 SNPs sufficed to maximize genomic prediction ability. We confirm the suitability of the apple REFPOP design for genomics-assisted breeding, especially for breeding programs using related germplasm, and emphasize the advantages of a coordinated and multinational effort for customizing apple breeding methods in the genomics era.

Role of Intact Hydrogen-Bond Networks in Multiproton-Coupled Electron Transfer.

The essential role of a well-defined hydrogen-bond network in achieving chemically reversible multiproton translocations triggered by one-electron electrochemical oxidation/reduction is investigated by using pyridylbenzimidazole-phenol models. The two molecular architectures designed for these studies differ with respect to the position of the N atom on the pyridyl ring. In one of the structures, a hydrogen-bond network extends uninterrupted across the molecule from the phenol to the pyridyl group. Experimental and theoretical evidence indicates that an overall chemically reversible two-proton-coupled electron-transfer process (E2PT) takes place upon electrochemical oxidation of the phenol. This E2PT process yields the pyridinium cation and is observed regardless of the cyclic voltammogram scan rate. In contrast, when the hydrogen-bond network is disrupted, as seen in the isomer, at high scan rates (∼1000 mV s-1) a chemically reversible process is observed with an E1/2 characteristic of a one-proton-coupled electron-transfer process (E1PT). At slow cyclic voltammetric scan rates (<1000 mV s-1) oxidation of the phenol results in an overall chemically irreversible two-proton-coupled electron-transfer process in which the second proton-transfer step yields the pyridinium cation detected by infrared spectroelectrochemistry. In this case, we postulate an initial intramolecular proton-coupled electron-transfer step yielding the E1PT product followed by a slow, likely intermolecular chemical step involving a second proton transfer to give the E2PT product. Insights into the electrochemical behavior of these systems are provided by theoretical calculations of the electrostatic potentials and electric fields at the site of the transferring protons for the forward and reverse processes. This work addresses a fundamental design principle for constructing molecular wires where protons are translocated over varied distances by a Grotthuss-type mechanism.

Genomic prediction of fruit texture and training population optimization towards the application of genomic selection in apple.

Texture is a complex trait and a major component of fruit quality in apple. While the major effect of MdPG1, a gene controlling firmness, has already been exploited in elite cultivars, the genetic basis of crispness remains poorly understood. To further improve fruit texture, harnessing loci with minor effects via genomic selection is therefore necessary. In this study, we measured acoustic and mechanical features in 537 genotypes to dissect the firmness and crispness components of fruit texture. Predictions of across-year phenotypic values for these components were calculated using a model calibrated with 8,294 SNP markers. The best prediction accuracies following cross-validations within the training set of 259 genotypes were obtained for the acoustic linear distance (0.64). Predictions for biparental families using the entire training set varied from low to high accuracy, depending on the family considered. While adding siblings or half-siblings into the training set did not clearly improve predictions, we performed an optimization of the training set size and composition for each validation set. This allowed us to increase prediction accuracies by 0.17 on average, with a maximal accuracy of 0.81 when predicting firmness in the 'Gala' × 'Pink Lady' family. Our results therefore identified key genetic parameters to consider when deploying genomic selection for texture in apple. In particular, we advise to rely on a large training population, with high phenotypic variability from which a 'tailored training population' can be extracted using a priori information on genetic relatedness, in order to predict a specific target population.

Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor.

Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KOtBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of N-methyl-N-arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction. The HE anion can be easily prepared in situ by reaction of the corresponding HE with KOtBu in DMSO at rt. Both protocols were further explored in terms of synthetic scope as well as mechanistic aspects to rationalize key features of desulfonylation processes. Furthermore, the HE anion induces reductive dehalogenation reaction of aryl halides under visible light irradiation.

The Multisite PeachRefPop Collection: A True Cultural Heritage and International Scientific Tool for Fruit Trees.

Plants have evolved a range of adaptive mechanisms that adjust their development and physiology to variable external conditions, particularly in perennial species subjected to long-term interplay with the environment. Exploiting the allelic diversity within available germplasm and leveraging the knowledge of the mechanisms regulating genotype interaction with the environment are crucial to address climatic challenges and assist the breeding of novel cultivars with improved resilience. The development of multisite collections is of utmost importance for the conservation and utilization of genetic materials and will greatly facilitate the dissection of genotype-by-environment interaction. Such resources are still lacking for perennial trees, especially with the intrinsic difficulties of successful propagation, material exchange, and living collection maintenance. This work describes the concept, design, and realization of the first multisite peach (Prunus persica) reference collection (PeachRefPop) located across different European countries and sharing the same experimental design. Other than an invaluable tool for scientific studies in perennial species, PeachRefPop provides a milestone in an international collaborative project for the conservation and exploitation of European peach germplasm resources and, ultimately, as a true heritage for future generations.

Aroma Investigation of New and Standard Apple Varieties Grown at Two Altitudes Using Gas Chromatography-Mass Spectrometry Combined with Sensory Analysis.

The aromatic profile of apples constitutes important information for the characterization and description of local products. Apple flavor is determined by perception in mouth and aroma; while the first is mainly defined by sugars and organic acids, aroma is a complex mixture of many volatile organic compounds (VOCs) whose composition is often specific to the variety. Headspace-solid phase microextraction gas chromatography coupled with mass spectrometry (HS-SPME-GC-MS) allows for the detection of detailed information of volatile constituents. In this study, eleven apple varieties (Braeburn, Fuji, Gala, Golden Delicious, Coop 39-Crimson Crisp®, Dalinette-Choupette®, Fujion, CIV323-Isaaq®, Coop43-Juliet®, SQ159-Natyra®, UEB32642-Opal®) grown in two pedoclimatic locations at different altitudes in South Tyrol (Italy) (ca. 225 m and ca. 650 m a.s.l.) were investigated. Thirty-eight VOCs were identified and combined with sensory analysis results (from 11 trained panelist) to characterize the aroma of new and standard apple varieties with a special focus on pedoclimatic location differences. The study shows strong diversification of the varieties based on their VOC profiles and sensory attributes, as expected. Moreover, investigating how the pedoclimatic location at different altitudes can influence the apple aroma profile, we identified twelve VOCs involved in these differences and provided a deeper investigation on how different altitudes can influence the apple aroma composition and perceptions combining the analytical and sensory parameters.

Ten Years of VINQUEST: First Insight for Breeding New Apple Cultivars With Durable Apple Scab Resistance.

Apple scab, caused by Venturia inaequalis, is a major fungal disease worldwide. Cultivation of scab-resistant cultivars would reduce the chemical footprint of apple production. However, new apple cultivars carrying durable resistances should be developed to prevent or at least slow the breakdown of resistance against races of V. inaequalis. One way to achieve durable resistance is to pyramid multiple scab resistance genes in a cultivar. The choice of the resistance genes to be combined in the pyramids should take into account the frequency of resistance breakdown and the geographical distribution of apple scab isolates able to cause such breakdowns. In order to acquire this information and to make it available to apple breeders, the VINQUEST project (www.vinquest.ch) was initiated in 2009. Ten years after launching this project, 24 partners from 14 countries regularly contribute data. From 2009 to 2018, nearly 9,000 data points have been collected. This information has been used to identify the most promising apple scab resistance genes for developing cultivars with durable resistance, which to date are: Rvi5, Rvi11, Rvi12, Rvi14, and Rvi15. As expected, Rvi1, together with Rvi3 and Rvi8, were often overcome, and have little value for scab resistance breeding. Rvi10 may also belong to this group. On the other hand, Rvi2, Rvi4, Rvi6, Rvi7, Rvi9, and Rvi13 are still useful for breeding, but their use is recommended only in extended pyramids of ≥3 resistance genes.

Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles.

A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39-85%). Theoretical combined with experimental studies led us to propose a probable polar mechanism (concerted SNAr).

Deciphering the genetic control of fruit texture in apple by multiple family-based analysis and genome-wide association.

Fruit texture is a complex feature composed of mechanical and acoustic properties relying on the modifications occurring in the cell wall throughout fruit development and ripening. Apple is characterized by a large variation in fruit texture behavior that directly impacts both the consumer's appreciation and post-harvest performance. To decipher the genetic control of fruit texture comprehensively, two complementing quantitative trait locus (QTL) mapping approaches were employed. The first was represented by a pedigree-based analysis (PBA) carried out on six full-sib pedigreed families, while the second was a genome-wide association study (GWAS) performed on a collection of 233 apple accessions. Both plant materials were genotyped with a 20K single nucleotide polymorphism (SNP) array and phenotyped with a sophisticated high-resolution texture analyzer. The overall QTL results indicated the fundamental role of chromosome 10 in controlling the mechanical properties, while chromosomes 2 and 14 were more associated with the acoustic response. The latter QTL, moreover, showed a consistent relationship between the QTL-estimated genotypes and the acoustic performance assessed among seedlings. The in silico annotation of these intervals revealed interesting candidate genes potentially involved in fruit texture regulation, as suggested by the gene expression profile. The joint integration of these approaches sheds light on the specific control of fruit texture, enabling important genetic information to assist in the selection of valuable fruit quality apple varieties.

Synthesis of Dibenzosultams by "Transition-Metal-Free" Photoinduced Intramolecular Arylation of N-Aryl-2-halobenzenesulfonamides.

A new and general synthetic route to prepare dibenzosultams is here reported. This approach involves the synthesis of N-aryl-2-halobenzenesulfonamides (3), followed by intramolecular C-C photoinduced arylation under soft conditions without the use of "Transition Metal". The photostimulated reactions exhibit very good tolerance to different substituent groups with good to excellent isolated yields (42-98%) of products. Moreover, it is shown that LED (λ = 395 nm) is an efficient light energy source to initiate efficiently the reactions. Theoretical inspection of the mechanism was made to probe the involvement of the radical-anion SRN1 process.

Chemodiversity in the fingerprint analysis of volatile organic compounds (VOCs) of 35 old and 7 modern apple cultivars determined by proton-transfer-reaction mass spectrometry (PTR-MS) in two different seasons.

Volatile organic compounds (VOCs) are chemical species that play an important role in determining the characteristic aroma and flavor of fruits. Apple (Malus × domestica Borkh.) cultivars differ in their aroma and composition of VOCs. To determine varietal differences in the aroma profiles, VOCs emitted by 7 modern and 35 old apple cultivars were analyzed using Proton Transfer Reaction Mass Spectrometry (PTR-MS). PTR-MS is a rapid, reproducible, and non-destructive spectrometric technique for VOC analysis of single fruits, developed for direct injection analysis. In the present study, we analyzed the differences in the emission of VOCs from single fruits at harvest and after a storage period of 60±10 days, followed by 3 d of shelf life. Our results show that VOC profile differences among apple cultivars were more pronounced after storage than at harvest. Furthermore, chemodiversity was higher in old cultivars compared to modern cultivars, probably due to their greater genetic variability. Our data highlight the importance of storage and shelf life are crucial for the development of the typical aroma and flavor of several apple cultivars. The validity of the method is demonstrated by comparison of two different harvest years.

"Transition-metal-free" synthesis of carbazoles by photostimulated reactions of 2'-halo[1,1'-biphenyl]-2-amines.

An efficient and simple protocol for the preparation of a series of 9H-carbazoles by photostimulated SRN1 substitution reactions is presented. Substituted 9H-carbazoles were synthesized in low to excellent yields (up to 96%) through an intramolecular C­N bond formation of 2'-halo[1,1'-biphenyl]-2-amines by the photoinitiated SRN1 mechanism under mild and "transition-metal-free" conditions. The biphenylamines used as substrates were obtained with isolated yields ranging from 21% to 84% by two approaches: (A) the cross-coupling Suzuki­Miyaura reaction and (B) the radical arylation of anilines. Some key aspects of the proposed mechanism were evaluated at the B3LYP/6-311+G* level.