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Aromatic rings form energetically favorable interactions with many polar groups in chemical and biological systems. Recent molecular studies have shown that sulfonamides can chelate metal ions and form hydrogen bonds, however, it is presently not established whether the polar sulfonamide functionality also interacts with aromatic rings. Here, synthetic, spectroscopic, structural, and quantum chemical analyses on 2,6-diarylbenzenesulfonamides are reported, in which two flanking aromatic rings are positioned close to the central sulfonamide moiety. Fine-tuning the aromatic character by substituents on the flanking rings leads to linear trends in acidity and proton affinity of sulfonamides. This physical-organic chemistry study demonstrates that aromatic rings have a capacity to stabilize sulfonamides via through-space NH–π interactions. These results have implications in rational drug design targeting electron-rich aromatic rings in proteins.

The construction of macromolecular hosts that are able to thread chiral guests in a stereoselective fashion is a big challenge. We herein describe the asymmetric synthesis of two enantiomeric C2-symmetric porphyrin macrocyclic hosts that thread and bind different viologen guests. Time-resolved fluorescence studies show that these hosts display a factor 3 kinetic preference (ΔΔG‡on = 3 kJ mol−1) for threading onto the different enantiomers of a viologen guest appended with bulky chiral 1-phenylethoxy termini. A smaller kinetic selectivity (ΔΔG‡on = 1 kJ mol−1) is observed for viologens equipped with small chiral sec-butoxy termini. Kinetic selectivity is absent when the C2-symmetric hosts are threaded onto chiral viologens appended with chiral tails in which the chiral moieties are located in the centers of the chains, rather than at the chain termini. The reason is that the termini of the latter guests, which engage in the initial stages of the threading process (entron effect), cannot discriminate because they are achiral, in contrast to the chiral termini of the former guests. Finally, our experiments show that the threading and de-threading rates are balanced in such a way that the observed binding constants are highly similar for all the investigated host–guest complexes, i.e. there is no thermodynamic selectivity., Chiral guests display kinetic stereoselective threading through chiral porphyrin cages if their chirality is located at the chain ends and not in the centers, supporting the previously reported entron effect of threading.

Contains fulltext : 235937.pdf (Publisher’s version ) (Open Access) 24 maart 2021

The product of a revealed transformation-NHC-ethynyl coupling-was observed as a catalyst transformation pathway in the Sonogashira cross-coupling, catalyzed by Pd/NHC complexes. The 2-ethynylated azolium salt was isolated in individual form and fully characterized, including X-ray analysis. A number of possible intermediates of this transformation with common formulae (NHC)n Pd(C2 Ph) (n=1,2) were observed and subjected to collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments to elucidate their structure. Measured bond dissociation energies (BDEs) and IRMPD spectra were in an excellent agreement with quantum calculations for coupling product π-complexes with Pd0 . Molecular dynamics simulations confirmed the observed multiple CID fragmentation pathways. An unconventional methodology to study catalyst evolution suggests the reported transformation to be considered in the development of new catalytic systems for alkyne functionalization reactions.

In traditional tissue engineering, synthetic or natural scaffolds are usually used as removable temporal support, which involves some biotechnology limitations. The concept of "scaffield" approach utilizing the physical fields instead of biomaterial scaffold has been proposed recently. In particular, a combination of intense magnetic and acoustic fields can enable rapid levitational bioassembly of complex-shaped 3D tissue constructs from tissue spheroids at low concentration of paramagnetic agent (gadolinium salt) in the medium. In the current study, the tissue spheroids from human bladder smooth muscle cells (myospheres) are used as building blocks for assembling the tubular 3D constructs. Levitational assembly is accomplished at low concentrations of gadolinium salts in the high magnetic field at 9.5 T. The biofabricated smooth muscle constructs demonstrate contraction after the addition of vasoconstrictive agent endothelin-1. Thus, hybrid magnetoacoustic levitational bioassembly is considered as a new technology platform in the emerging field of formative biofabrication. This novel technology of scaffold-free, nozzle-free, and label-free bioassembly opens a unique opportunity for rapid biofabrication of 3D tissue and organ constructs with complex geometry.

This Minireview highlights the application of electrospray ionization mass spectrometry (ESI-MS) to investigating photochemical reactions. We show possible approaches to on-line ESI-MS monitoring of photocatalytic reactions and give examples of the characterization of short-lived photochemical intermediates by ion spectroscopy. The minireview also exemplifies in-depth mass spectrometric studies of photoisomerization reactions and photofragmentation reactions. Apart from mechanistic studies, the coupling of photochemistry and mass spectrometry is a powerful approach to studying structure and properties of biomolecules. We show several examples focused on investigation of intrinsic properties of model biomolecules.

Diaurated intermediates of gold-catalysed reactions have been a long-standing subject of debate. Although diaurated complexes were regarded as a drain of active monoaurated intermediates in catalytic cycles, they were also identified as the products of gold–gold cooperation in dual–activation reactions. This study shows investigation of intermediates in water addition to alkynes catalysed by [(IPr)Au(CH3CN)(BF4)]. Electrospray ionisation mass spectrometry (ESI-MS) allowed us to detect both monoaurated and diaurated complexes in this reaction. Infrared photodissociation spectra of the trapped complexes show that the structure of the intermediates corresponds to α-gold ketone intermediates protonated or aurated at the oxygen atom. Delayed reactant labelling experiments provided the half life of the intermediates in reaction of 1-phenylpropyne (∼7 min) and the kinetic isotope effects for hydrogen introduction to the carbon atom (KIE ∼ 4–6) and for the protodeauration (KIE ∼ 2). The results suggest that the ESI-MS detected monoaurated and diaurated complexes report on species with a very similar or the same kinetics in solution. Kinetic analysis of the overall reaction showed that the reaction rate is first-order dependent on the concentration of the gold catalyst. Finally, all results are consistent with the reaction mechanism proceeding via monoaurated neutral α-gold ketone intermediates only., Reaction kinetics and detected α-gold ketone intermediates reveal that gold-mediated hydration of alkynes does not rely on dual activation.

We report and analyze chemoselectivity in the gas phase reactions of cycloalkenes (cyclohexene, cycloheptene, cis-cyclooctene, 1,4-cyclohexadiene) with a non-heme iron(IV)-oxo complex [(PyTACN)Fe(O)(Cl)]+, which models the active species in iron-dependent halogenases. Unlike in the halogenases, we did not observe any chlorination of the substrate. However, we observed two other reaction pathways: allylic hydrogen atom transfer (HAT) and alkene epoxidation. The HAT is clearly preferred in the case of 1,4-cyclohexadiene, both pathways have comparable reaction rates in reaction with cyclohexene, and epoxidation is strongly favored in reactions with cycloheptene and cis-cyclooctene. This preference for epoxidation differs from the reactivity of iron(IV)-oxo complexes in the condensed phase, where HAT usually prevails. To understand the observed selectivity, we analyze effects of the substrate, spin state, and solvation. Our DFT and CASPT2 calculations suggest that all the reactions occur on the quintet potential energy surface. The DFT-calculated energies of the transition states for the epoxidation and hydroxylation pathways explain the observed chemoselectivity. The SMD implicit solvation model predicts the relative increase of the epoxidation barriers with solvent polarity, which explains the clear preference of HAT in the condensed phase. Electronic supplementary material The online version of this article (10.1007/s13361-019-02251-1) contains supplementary material, which is available to authorized users.

Helium tagging of charged C60q+ ions (q = 1–3) has been used for measuring electronic and infrared gas phase spectra, allowing astronomers to improve the identification of fullerenes in space. Here, we present a detailed study of the attachment of He to cold mass selected fullerene ions. Experiments were performed in the temperature variable radio frequency (rf) ion trap ISORI at high He densities and a few K. For all three charge states, the ternary rate coefficients for forming He-C60q+ are below 10−31 cm6s–1 and all three show temperature dependences, proportional to exp(-T/T0) with T0.

Gold π-complexes have been studied largely in the past 2 decades because of their role in gold-catalyzed reactions. We report an experimental and theoretical investigation of the interaction between a wide range of unsaturated hydrocarbons (alkanes, alkynes, alkadienes, and allenes) and triphenylphosphine-gold(I), triphenylphosphine-silver(I), and acetonitrile-silver(I) cations. The bond dissociation energies of these complexes were determined by mass spectrometry collision-induced dissociations and their structures were studied by density functional theory calculations and infrared photodissociation spectroscopy. The results show that with the same phosphine ligand, gold binds stronger to the π-ligands than silver and thereby activates the unsaturated bond more effectively. Ligand exchange of phosphine by acetonitrile at the silver complexes increases the binding energy as well as the activation of the π-ligands. We also show that the substitution of an unsaturated bond is more important than the bond type.

In the last decade, organoid technology has developed as a primary research tool in basic biological and clinical research. The reliance on poorly defined animal‐derived extracellular matrix, however, severely limits its application in regenerative and translational medicine. Here, a well‐defined, synthetic biomimetic matrix based on polyisocyanide (PIC) hydrogels that support efficient and reproducible formation of mammary gland organoids (MGOs) in vitro is presented. Only decorated with the adhesive peptide RGD for cell binding, PIC hydrogels allow MGO formation from mammary fragments or from purified single mammary epithelial cells. The cystic organoids maintain their capacity to branch for over two months, which is a fundamental and complex feature during mammary gland development. It is found that small variations in the 3D matrix give rise to large changes in the MGO: the ratio of the main cell types in the MGO is controlled by the cell–gel interactions via the cell binding peptide density, whereas gel stiffness controls colony formation efficiency, which is indicative of the progenitor density. Simple hydrogel modifications will allow for future introduction and customization of new biophysical and biochemical parameters, making the PIC platform an ideal matrix for in depth studies into organ development and for application in disease models., A fully synthetic and highly tailorable matrix material is presented that supports the formation of organoids. With minimal adhesive peptide functionalization, this polyisocyanide hydrogel allows single cells to develop into mammary gland organoids. As tuning the hydrogel properties controls organoid composition, future customization will set the stage for improved control of organoid production and in‐depth studies into organ development.

Biological materials combine stress relaxation and self-healing with non-linear stress-strain responses. These characteristic features are a direct result of hierarchical self-assembly, which often results in fiber-like architectures. Even though structural knowledge is rapidly increasing, it has remained a challenge to establish relationships between microscopic and macroscopic structure and function. Here, we focus on understanding how network topology determines the viscoelastic properties, i.e., stress relaxation, of biomimetic hydrogels. We have dynamically crosslinked two different synthetic polymers with one and the same crosslink. The first polymer, a polyisocyanopeptide (PIC), self-assembles into semi-flexible, fiber-like bundles, and thus displays stress-stiffening, similar to many biopolymer networks. The second polymer, 4-arm poly(ethylene glycol) (starPEG), serves as a reference network with well-characterized structural and viscoelastic properties. Using one and the same coiled coil crosslink allows us to decouple the effects of crosslink kinetics and network topology on the stress relaxation behavior of the resulting hydrogel networks. We show that the fiber-containing PIC network displays a relaxation time approximately two orders of magnitude slower than the starPEG network. This reveals that crosslink kinetics is not the only determinant for stress relaxation. Instead, we propose that the different network topologies determine the ability of elastically active network chains to relax stress. In the starPEG network, each elastically active chain contains exactly one crosslink. In the absence of entanglements, crosslink dissociation thus relaxes the entire chain. In contrast, each polymer is crosslinked to the fiber bundle in multiple positions in the PIC hydrogel. The dissociation of a single crosslink is thus not sufficient for chain relaxation. This suggests that tuning the number of crosslinks per elastically active chain in combination with crosslink kinetics is a powerful design principle for tuning stress relaxation in polymeric materials. The presence of a higher number of crosslinks per elastically active chain thus yields materials with a slow macroscopic relaxation time but fast dynamics at the microscopic level. Using this principle for the design of synthetic cell culture matrices will yield materials with excellent long-term stability combined with the ability to locally reorganize, thus facilitating cell motility, spreading, and growth. ispartof: FRONTIERS IN CHEMISTRY vol:8 ispartof: location:Switzerland status: published

Leaving groups attached to the meso-methyl position of many common dyes, such as xanthene, BODIPY, or pyronin derivatives, can be liberated upon irradiation with visible light. However, the course of phototransformations of such photoactivatable systems can be quite complex and the identification of reaction intermediates or even products is often neglected. This paper exemplifies the photochemistry of a 9-dithianyl-pyronin derivative, which undergoes an oxidative transformation at the meso-position to give a 3,6-diamino-9H-xanthen-9-one derivative, formic acid, and carbon monoxide as the main photoproducts. The course of this multi-photon multi-step reaction was studied under various conditions by steady-state and time-resolved optical spectroscopy, mass spectrometry and NMR spectroscopy to understand the effects of solvents and molecular oxygen on individual steps. Our analyses have revealed the existence of many intermediates and their interrelationships to provide a complete picture of the transformation, which can bring new inputs to a rational design of new photoactivatable pyronin or xanthene derivatives. Odstupující skupiny připojené k meso-methyl pozici mnoha běžných barviv (např. xanthen, BOPIDY nebo deriváty pyroninu) mohou odstupovat při ozáření viditelným světlem. Nicméně proces fototransformace takových fotoaktivovatelných systémů může být poměrně složitý a tak identifikace reakčních meziproduktů nebo dokonce produktů je často opomíjena. Tato publikace osvětluje fotochemii derivátu 9-dithianylpyroninu, který podléhá oxidativní transformaci na meso-pozici za vzniku 3,6-diamino-9H-xanthen-9-onu, kyseliny mravenčí a oxidu uhelnatého jako hlavních fotoproduktů. Průběh této multifotonové vícestupňové reakce byl studován za různých podmínek optickou spektroskopií v ustáleném a časově rozlišeném spektru, hmotnostní spektrometrií a NMR spektroskopií za účelem pochopení vlivu rozpouštědel a molekulárního kyslíku na jednotlivé kroky. Naše analýzy odhalily existenci mnoha meziproduktů a jejich vztahy poskytují celkový obraz transformace, která může přinést nové informace pro desing nových fotoaktivovatelných derivátů pyroninu a xanthenu.

Iron(IV)‐oxo intermediates in nature contain two unpaired electrons in the Fe–O antibonding orbitals, which are thought to contribute to their high reactivity. To challenge this hypothesis, we designed and synthesized closed‐shell singlet iron(IV) oxo complex [(quinisox)Fe(O)]+ (1+; quinisox‐H=(N‐(2‐(2‐isoxazoline‐3‐yl)phenyl)quinoline‐8‐carboxamide). We identified the quinisox ligand by DFT computational screening out of over 450 candidates. After the ligand synthesis, we detected 1+ in the gas phase and confirmed its spin state by visible and infrared photodissociation spectroscopy (IRPD). The Fe–O stretching frequency in 1+ is 960.5 cm−1, consistent with an Fe–O triple bond, which was also confirmed by multireference calculations. The unprecedented bond strength is accompanied by high gas‐phase reactivity of 1+ in oxygen atom transfer (OAT) and in proton‐coupled electron transfer reactions. This challenges the current view of the spin‐state driven reactivity of the Fe–O complexes., An iron oxo complex with an Fe≡O bond and a closed shell ground state was designed by employing DFT calculations, synthesized, and experimentally characterized by gas‐phase spectroscopic techniques. Despite the unprecedented Fe≡O bond strength and closed‐shell ground state, it still exhibits high‐reactivity.

The mechanism of oxidation of arylamines by copper enzymes is not clarified yet. Here, we explored a reaction between a possible high-valent copper(II)-oxyl intermediate and arylamine. We have employed a TPA ligand (TPA = tris(2-pyridylmethyl)amine) with the NH2 group in position 2 of one of the pyridine rings (TPANH2). This model system allows generation of [(TPANH2)Cu(O)]+ in the gas phase, which immediately undergoes a reaction between the arylamino group and the copper oxyl moiety. The reaction leads to elimination of H2O and formation of a copper–nitrene complex. The structure of the resulting copper–nitrene complex was confirmed by infrared spectroscopy in the gas phase. We show that the copper–nitrene complex reacts by hydrogen atom transfer with 1,4-cyclohexadiene and by an order of magnitude faster by a double hydrogen atom transfer with ethanethiol and methanol. DFT calculations explain the formation of the copper nitrene as well as its reactivity in agreement with the experimental findings.

Development of new reactions requires finding and understanding of novel reaction pathways. In challenging reactions such as C–H activations, these pathways often involve highly reactive intermediates which are the key to our understanding, but difficult to study. Mass spectrometry has a unique sensitivity for detecting low abundant charged species; therefore it is increasingly used for detection of such intermediates in metal catalysed- and organometallic reactions. This perspective shows recent developments in the field of mass spectrometric research of reaction mechanisms with a special focus on going beyond mass-detection. Chapters discuss the advantages of collision-induced dissociation, ion mobility and ion spectroscopy for characterization of structures of the detected intermediates. In addition, we discuss the relationship between the condensed phase chemistry and mass spectrometric detection of species from solution., Modern approaches of mass spectrometry can identify reaction intermediates and provide a unique insight into their structure, properties and kinetics.

The formation and detailed spectroscopic characterization of the first biuret-containing monoanionic superoxido-NiII intermediate [LNiO2 ]- as the Li salt [2; L=MeN[C(=O)NAr)2 ; Ar=2,6-iPr2 C6 H3 )] is reported. It results from oxidation of the corresponding [Li(thf)3 ]2 [LNiII Br2 ] complex M with excess H2 O2 in the presence of Et3 N. The [LNiO2 ]- core of 2 shows an unprecedented nucleophilic reactivity in the oxidative deformylation of aldehydes, in stark contrast to the electrophilic character of the previously reported neutral Nacnac-containing superoxido-NiII complex 1, [L'NiO2 ] (L'=CH(CMeNAr)2 ). According to density-functional theory (DFT) calculations, the remarkably different behaviour of 1 versus 2 can be attributed to their different charges and a two-state reactivity, in which a doublet ground state and a nearby spin-polarized doublet excited-state both contribute in 1 but not in 2. The unexpected nucleophilicity of the superoxido-NiII core of 2 suggests that such a reactivity may also play a role in catalytic cycles of Ni-containing oxygenases and oxidases.

This paper reports gas-phase IR spectra of (n = 1–3) ions in the range from 1100 to 1600 cm−1. The spectra were recorded with a temperature-variable radio frequency ion trap instrument. The experiments work with mass-selected ions confined in a linear wire quadrupole, where they form helium-tagged complexes following exposure to low-temperature (as low as 2.3 K) and high-density helium buffer gas. All measured lines are homogeneously broadened owing to a strong coupling between the vibrational states of the fullerene cage. The short lifetimes of picoseconds or below rule out measurements of high-resolution IR spectra. Reproducible sidebands with distances between 5 and 20 cm−1 enrich the spectra. Tentative explanations are based on nonlinear and symmetry-breaking interactions or may be due to the influence of the attached He atom. Comparison of the spectrum with that of reveals shifts up to 6 cm−1, while the IR spectra of and are very similar. With the harmonic potential of the trap the ions are squeezed into the rather narrow laser beam, increasing the sensitivity and simplifying the determination of absolute photoabsorption cross sections. Disregarding shifts of several cm−1, the gas-phase results for and are in agreement with previous matrix results and with theoretical predictions. The astrophysical relevance of our results is briefly mentioned.

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Contains fulltext : 205348.pdf (Publisher’s version ) (Open Access) Wounds often result in scarring, prolonged morbidity, and loss of function. New interactive and modifiable hydrogel wound dressings are being developed for these injuries. Polyisocyanopeptide (PIC) gel is a promising thermosensitive hydrogel having several characteristics that can facilitate wound repair, including ease of application/removal and strain-stiffening properties that mimic extracellular matrix components. However, it is unknown whether the PIC gel remains in the wound for a clinically relevant time period. Therefore, PIC polymers were functionalized with a DTPA group allowing labelling with Indium-111 (111In). Following application of this radiolabelled gel to splinted and non-splinted murine full-thickness skin wounds the signal was monitored using SPECT/CT imaging for 7 days. The SPECT signal from the PIC gel was highly stable and covered the complete wound area. Non-bound 111In-EDTA was rapidly cleared via the kidneys to the urine. The impact of PIC gels on wound repair was further studied visually and histologically. Radiolabelled PIC gel was observed to move both over and under the skin, while histological analysis demonstrated that part of the gel became encapsulated within the wound repair tissue, but did not delay wound closure or otherwise impair wound healing. This work illustrates for the first time the use of 111In-labelled PIC gels for diagnostic and monitoring purposes and describes the use of PIC in the (non-)splinted murine skin wound model. It was found that PIC gels remained in splinted and non-splinted full-thickness skin wounds during wound repair. This warrants the continuation of developing the PIC gel into a clinically advanced wound dressing.

Flavin‐based catalysts are photoactive in the visible range which makes them useful in biology and chemistry. Herein, we present electrospray‐ionization mass‐spectrometry detection of short‐lived intermediates in photooxidation of toluene catalysed by flavinium ions (Fl+). Previous studies have shown that photoexcited flavins react with aromates by proton‐coupled electron transfer (PCET) on the microsecond time scale. For Fl+, PCET leads to FlH.+ with the H‐atom bound to the N5 position. We show that the reaction continues by coupling between FlH.+ and hydroperoxy or benzylperoxy radicals at the C4a position of FlH.+. These results demonstrate that the N5‐blocking effect reported for alkylated flavins is also active after PCET in these photocatalytic reactions. Structures of all intermediates were fully characterised by isotopic labelling and by photodissociation spectroscopy. These tools provide a new way to study reaction intermediates in the sub‐second time range., Active site switch occurred after N5‐hydrogen blocking which resulted from proton coupled electron transfer. The short‐lived peroxy‐flavinium reaction intermediates were characterised by mass spectrometry and ion spectroscopy. Although the effect of N5‐hydrogen blocking was predicted more than 40 years ago, this is the first direct evidence.

One of the promises of synthetic materials in cell culturing is that control over their molecular structures may ultimately be used to control their biological processes. Synthetic polymer hydrogels from polyisocyanides (PIC) are a new class of minimal synthetic biomaterials for three-dimensional cell culturing. The macromolecular lengths and densities of biofunctional groups that decorate the polymer can be readily manipulated while preserving the intrinsic nonlinear mechanics, a feature commonly displayed by fibrous biological networks. In this work, we propose the use of PIC gels as cell culture platforms with decoupled mechanical inputs and biological cues. For this purpose, different types of cells were encapsulated in PIC gels of tailored compositions that systematically vary in adhesive peptide (GRGDS) density, polymer length, and concentration; with the last two parameters controlling the gel mechanics. Both cancer and smooth muscle cells grew into multicellular spheroids with proliferation rates that depend on the adhesive GRGDS density, regardless of the polymer length, suggesting that for these cells, the biological input prevails over the mechanical cues. In contrast, human adipose-derived stem cells do not form spheroids but rather spread out. We find that the morphological changes strongly depend on the adhesive ligand density and the network mechanics; gels with the highest GRGDS densities and the strongest stiffening response to stress show the strongest spreading. Our results highlight the role of the nonlinear mechanics of the extracellular matrix and its synthetic mimics in the regulation of cell functions.

Aquest mateix article està publicat a l'edició alemanya d''Angewandte Chemie' (ISSN 0044-8249, EISSN 1521-3757), 2019, vol.131, núm. 28, p. 9721-9726. DOI https://doi.org/10.1002/ange.201904546 Terminal oxo complexes of late transition metals are frequently proposed reactive intermediates. However, they are scarcely known beyond Group 8. Using mass spectrometry, we prepared and characterized two such complexes: [(N4Py)CoIII(O)]+ (1) and [(N4Py)CoIV(O)]2+ (2). Infrared photodissociation spectroscopy revealed that the Co−O bond in 1 is rather strong, in accordance with its lack of chemical reactivity. On the contrary, 2 has a very weak Co−O bond characterized by a stretching frequency of ≤659 cm−1. Accordingly, 2 can abstract hydrogen atoms from non-activated secondary alkanes. Previously, this reactivity has only been observed in the gas phase for small, coordinatively unsaturated metal complexes. Multireference ab-initio calculations suggest that 2, formally a cobalt(IV)-oxo complex, is best described as cobalt(III)-oxyl. Our results provide important data on changes to metal-oxo bonding behind the oxo wall and show that cobalt-oxo complexes are promising targets for developing highly active C−H oxidation catalysts The project was funded by the European Research Council (ERC CoG No. 682275), the Czech Ministry of Education, Youth and Sports (LTAUSA17026), the COST action ECOSTBio, MINECO of Spain (CTQ2015‐70795‐P), the Catalan DIUE of the Generalitat de Catalunya (2017SGR01378, a BFI PhD grant to M.R., and an ICREA‐Academia award), and the Grant Agency of the Czech Republic (Grant No. 18‐13093S)

Despite substantial evidence of short Au⋅⋅⋅H-X contacts derived from a number of X-ray structures of AuI compounds, the nature of AuI ⋅⋅⋅H bonding in these systems has not been clearly understood. Herein, we present the first spectroscopic evidence for an intramolecular AuI ⋅⋅⋅H+ -N hydrogen bond in a [Cl-Au-L]+ complex, where L is a protonated N-heterocyclic carbene. The complex was isolated in the gas phase and characterized with helium-tagging infrared photodissociation (IRPD) spectra, in which H+ -N-mode-derived bands evidence the intramolecular AuI ⋅⋅⋅H+ -N bond. Quantum chemical calculations reproduce the experimental IRPD spectra and allow to characterize the intramolecular Au⋅⋅⋅H+ -N bonding with a short rAu⋅⋅⋅H distance of 2.17 A and an interaction energy of approximately -10 kcal mol-1 . Various theoretical descriptors of chemical bonding calculated for the Au⋅⋅⋅H+ -N interaction provide strong evidence for a hydrogen bond of moderate strength.

Finding optimal reaction conditions is usually complex, requires many experiments, and is therefore demanding in terms of human, financial, and environmental resources. This work provides a simple workflow for easier design of popular palladium-catalyzed C−H functionalization reactions, where the active palladium catalysts contain carboxylate ligands. The key factor for optimizing reaction conditions is to find a balance between two opposing effects of the carboxylic acid in the reaction mixture: generation of more reactive palladium catalyst versus deactivation of a substrate by its protonation. Hledání optimální reakčních podmínek je obecně komplikované a vyžaduje mnoho experimentů a je také spojeno s nároky na lidské, finanční a environmentální zdroje. Tato práce poskytuje jednoduchý postup pro snažší návrh populárních palladiem katalyzovaných C–H funkcionalizačních reakcí, v nichž aktivní katalyzátory palladia obsahují karboxylátové ligandy. Klíčovým faktorem pro optimalizační podmínky je nalézt rovnováhu mezi dvěma protichůdnými účinky karboxylové kyseliny v reakční směsi: tvorba více reaktivního katalyzátoru palladia vs. deaktivace substrátu protonací.

The combination of cryogenic ion traps with suitable light sources and standard tools of mass spectrometry has led to many innovative applications in previous years. This paper presents the combination of our versatile instrument with a supercontinuum laser for the rapid identification of ions that might be of special interest, e.g. as candidates for diffuse interstellar bands carriers. Using a linear wire quadrupole ion trap at 3 K, routine He-tagging, long irradiation times, and the brilliance and wide spectral range of a crystal fiber laser, mass selected ions have been exposed to spectral fluencies larger than 10 mJ (nm cm2)−1. These conditions result in an unsurpassed sensitivity, allowing us to find out within a few minutes and with nm accuracy, where photo absorption occurs with cross sections above 10−18 cm2. In this contribution, we present a variety of ions, probed between 420 and 720 nm. They have been generated by electron- or electrospray ionization of (polycyclic) aromatic hydrocarbons. For selected candidates, we recorded spectra with higher resolution and in the IR range. The anthracene dication has been selected to present a detailed analysis of our new results., Combining He-tagging in a cryotrap with a supercontinuum laser is an efficient way of identifying candidates for DIBs carriers.

We report a system with ethylene-bridged flavinium salt 2b which catalyzes the aerobic oxidation of toluenes and benzyl alcohols with high oxidation potential (Eox > +2.5 V vs SCE) to give the corresponding benzoic acids under visible light irradiation. This is caused by the high oxidizing power of excited 2b (E(2b*) = +2.67 V vs SCE) involved in photooxidation and by the accompanying dark organocatalytic oxygenation provided by the in situ formed flavin hydroperoxide 2b-OOH.

The ruthenium complexes [Ru(CYM)(p-Cl-dkt)(Cl)] (1), [Ru(CYM)(pta)(p-Cl-dkt)]PF6 (2), and [Ru(CYM)(pta)Cl2] (3, RAPTA-C) (CYM = para-cymene, p-Cl-dkt = 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione, pta = 1,3,5-triaza-7-phosphaadamantane) are biologically active and show anti-cancer activities, albeit with different mechanisms. To further understand these mechanisms, we compared their speciation in aqueous solutions with an amino acid (cysteine), with an amino acid derivative (N-acetylcysteine) and with a tripeptide (glutathione) by Mass Spectrometry (MS). Here, we show that all ruthenium complexes have high selectivity for cysteine and cysteine-derived molecules. On one hand, [Ru(CYM)(p-Cl-dkt)(Cl)] undergoes solvolysis in water and forms [Ru2(CYM)2(OH)3]+. Subsequently, all hydroxyl anions are exchanged by deprotonated cysteine. Infrared Photodissociation Spectroscopy (IRPD) showed that cysteine binds to the ruthenium atoms via the deprotonated thiol group and that sulfur bridges the ruthenium centers. On the other hand, the pta-bearing complexes remain monometallic and undergo only slow Cl or p-Cl-dkt exchange by deprotonated cysteine. Therefore, the pta ligand protects the ruthenium complexes from ligand exchange with water and from the formation of biruthenium clusters, possibly explaining why the mechanism of pta-bearing ruthenium complexes is not based on ROS production but on their reactivity as monometallic complexes., ESI-MS study of ruthenium complexes shows their high selectivity toward thiol containing molecules and formation of larger thiolate-bound clusters in absence of a protecting ligand such as pta.

Polymer brushes are extensively used for the preparation of bioactive surfaces. They form a platform to attach functional (bio)molecules and control the physicochemical properties of the surface. These brushes are nearly exclusively prepared from flexible polymers, even though much stiffer brushes from semiflexible polymers are frequently found in nature, which exert bioactive functions that are out of reach for flexible brushes. Synthetic semiflexible polymers, however, are very rare. Here, we use polyisocyanopeptides (PICs) to prepare high-density semiflexible brushes on different substrate geometries. For bioconjugation, we developed routes with two orthogonal click reactions, based on the strain-promoted azide-alkyne cycloaddition reaction and the (photoactivated) tetrazole-ene cycloaddition reaction. We found that for high brush densities, multiple bonds between the polymer and the substrate are necessary, which was achieved in a block copolymer strategy. Whether the desired biomolecules are conjugated to the PIC polymer before or after brush formation depends on the dimensions and required densities of the biomolecules and the curvature of the substrate. In either case, we provide mild, aqueous, and highly modular reaction strategies, which make PICs a versatile addition to the toolbox for generating semiflexible bioactive polymer brush surfaces. ispartof: BIOMACROMOLECULES vol:20 issue:7 pages:2587-2597 ispartof: location:United States status: published

Morphogenesis is a tightly‐regulated developmental process by which tissues acquire the morphology that is critical to their function. For example, epithelial cells exhibit different 2D and 3D morphologies, induced by distinct biochemical and biophysical cues from their environment. In this work, novel hybrid matrices composed of a Matrigel and synthetic oligo(ethylene glycol)‐grafted polyisocyanides (PICs) hydrogels are used to form a highly tailorable environment. Through precise control of the stiffness and cell‐matrix interactions, while keeping other properties constant, a broad range of morphologies induced in Madin‐Darby Canine Kidney (MDCK) cells is observed. At relatively low matrix stiffness, a large morphological shift from round hollow cysts to 2D monolayers is observed, without concomitant translocation of the mechanotransduction protein Yes‐associated protein (YAP). At higher stiffness levels and enhanced cell‐matrix interactions, tuned by controlling the adhesive peptide density on PIC, the hybrid hydrogels induce a flattened cell morphology with simultaneous YAP translocation, suggesting activation. In 3D cultures, the latter matrices lead to the formation of tubular structures. Thus, mixed synthetic and natural gels, such as the hybrids presented here, are ideal platforms to dissect how external physical factors can be used to regulate morphogenesis in MDCK model system, and in the future, in more complex environments., The cellular environment plays a key role in determining tissue morphogenesis. This work uses hybrid matrices, composed of synthetic polyisocyanides (PICs) and Matrigel, that allows for precise control of matrix stiffness and cell‐matrix interactions. Variations in hybrid matrices induce a full spectrum of morphologies in Madin‐Darby canine kidney (MDCK) cells, and includes both YAP‐dependent and ‐independent processes.

Molecular recognition between polar groups and aromatic molecules is fundamentally important to rational drug design. Although it has been well established that many polar functionalities interact with electron‐rich aromatic residues through energetically favorable polar‐π interactions, there is a limited understanding of the association between thiols and aromatic systems. Herein we report physical‐organic chemistry studies on 2,6‐diarylthiophenols that possess the central thiophenol ring and two flanking aromatic rings with tunable electronic properties caused by substituents at distant para position. Hammett analysis revealed that pK a values and proton affinities correlate well with Hammett sigma values of substituents. Additional energy decomposition analysis supported the conclusion that both through‐space SH‐π interactions and S−‐π interactions contribute to intramolecular stabilization of 2,6‐diarylthiophenols., Understanding interactions: Despite a well‐established knowledge that polar‐π interactions play an important role in molecular recognition, it is currently poorly understood how thiols interact with aromatic systems. Our physical‐organic chemistry studies, based on measurements of pK a values, structural studies, and quantum chemical analyses, reveal that 2,6‐diarylthiophenols are stabilized by through‐space SH‐π interactions and S−‐π interactions.

Nucleotide prodrugs (ProTides) based on phosphate or phosphonate compounds are potent and successfully marketed antiviral drugs. Although their biological properties are well explored, experimental evidence on the mechanism of their activation pathway is still missing. In this study, we synthesized two ProTide analogues, which can be activated by UV light. Using 31P and 13C NMR spectroscopy with in situ irradiation, we followed the ProTide activation pathway in various solvents, and we detected the first proposed intermediate and the monoamidate product. Furthermore, we used mass spectrometry (MS) coupled with infrared spectroscopy in the gas phase to detect and to characterize the elusive cyclic pentavalent phosphorane and cyclic acyl phosphoramidate intermediates. Our combined NMR and MS data provided the first experimental evidence of the cyclic intermediates in the activation pathway of ProTide prodrugs.

The CuO+ core is a central motif of reactive intermediates in copper-catalysed oxidations occurring in nature. The high reactivity of CuO+ stems from a weak bonding between the atoms, which cannot be described by a simple classical model. To obtain the correct picture, we have investigated the acetonitrile-ligated CuO+ ion using neon-tagging photodissociation spectroscopy at 5 K. The spectra feature complex vibronic absorption progressions in NIR and visible regions. Employing Franck-Condon analyses, we derived low-lying triplet potential energy surfaces that were further correlated with multireference calculations. This provided insight into the ground and low-lying excited electronic states of the CuO+ unit and elucidated how these states are perturbed by the change in ligation. Thus, we show that the bare CuO+ ion has prevailingly a copper(I)-biradical oxygen character. Increasing the number of ligands coordinated to copper changes the CuO+ character towards the copper(II)-oxyl radical structure.

The synthesis and optical studies of a new chiral binaphthyl-based polymeric sensor are described herein. The polymers were prepared using the copper-catalyzed azide?alkyne cycloaddition reaction between fluorene and binaphthyl monomeric units. Resulted polymers differ in the orientation of the 1,2,3-triazole unit as a linker in polymeric backbone based on monomeric character. The responses of these polymers to both exposure to metal ions and the acidic medium were investigated by UV?vis absorbance, circular dichroism and fluorescence analysis. The changes in the absorption, chiroptical and fluorescence properties of the polymers indicate a change of the dihedral angle between the two naphthalene units on the binaphthyl moiety and tunability in conjugation. Moreover, an influence of regioselectivity of 1,2,3-triazole unit in polymer backbone in regards to complexation was discussed. The modulation in signal was detected in real time and makes this system a suitable candidate for further applications as an ion sensor or acid-responsive material The authors would like to thank Dr. I. Lacik (Polymer Institute, the Slovak Academy of Science, Slovakia) for generously providing the laboratory facilities in the initial stage of the studies. P.K. thanks to the NPRP award [ 8-878-1-172 ] from Qatar National Research Fund (a member of Qatar foundation). The statements made herein are solely the responsibility of the authors. Scopus

Terminal non-heme iron(IV)-oxo compounds are among the most powerful and best studied oxidants of strong C-H bonds. In contrast to the increasing number of such complexes (>80 thus far), corresponding one-electron-reduced derivatives are much rarer and presumably less stable, and only two iron(III)-oxo complexes have been characterized to date, both of which are stabilized by hydrogen-bonding interactions. Herein we have employed gas-phase techniques to generate and identify a series of terminal iron(III)-oxo complexes, all without built-in hydrogen bonding. Some of these complexes exhibit ∼70 cm-1 decrease in ν(Fe-O) frequencies expected for a half-order decrease in bond order upon one-electron reduction to an S = 5/2 center, while others have ν(Fe-O) frequencies essentially unchanged from those of their parent iron(IV)-oxo complexes. The latter result suggests that the added electron does not occupy a d orbital with Fe═O antibonding character, requiring an S = 3/2 spin assignment for the nascent FeIII-O- species. In the latter cases, water is found to hydrogen bond to the FeIII-O- unit, resulting in a change from quartet to sextet spin state. Reactivity studies also demonstrate the extraordinary basicity of these iron(III)-oxo complexes. Our observations show that metal-oxo species at the boundary of the "Oxo Wall" are accessible, and the data provide a lead to detect iron(III)-oxo intermediates in biological and biomimetic reactions.

Cross-coupling transformations are a powerful tool in organic synthesis. It is known that this kind of transformation undergoes 2- electron redox processes, and, for this reason, silver has been nearly forgotten as catalyst for cross-couplings because silver is mainly considered as a 1-electron redox metal. Herein, we disclose effective Ag(I)-catalyzed cross- coupling transformations using bidentate aminoquinoline as a directing group toward different nucleophiles to form C−C, C−N, and C−O bonds. DFT calculations indicate the feasible oxidative addition of L1-I substrate via the Ag(I)/Ag(III) catalytic cycle. Furthermore, ion spectroscopy experiments suggest a highly reactive aryl-Ag(III) that in the absence of nucleophiles reacts to form an intermolecular cyclic product [5d-Ag(I)-CH3CN], which in solution forms 5a. This work proves that silver can undergo 2-electron redox processes in cross-coupling reactions like Pd and Cu.

Reactivities of non‐heme iron(IV)‐oxo complexes are mostly controlled by the ligands. Complexes with tetradentate ligands such as [(TPA)FeO]2+ (TPA=tris(2‐pyridylmethyl)amine) belong to the most reactive ones. Here, we show a fine‐tuning of the reactivity of [(TPA)FeO]2+ by an additional ligand X (X=CH3CN, CF3SO3 −, ArI, and ArIO; ArI=2‐(tBuSO2)C6H4I) attached in solution and reveal a thus far unknown role of the ArIO oxidant. The HAT reactivity of [(TPA)FeO(X)]+/2+ decreases in the order of X: ArIO > MeCN > ArI ≈ TfO−. Hence, ArIO is not just a mere oxidant of the iron(II) complex, but it can also increase the reactivity of the iron(IV)‐oxo complex as a labile ligand. The detected HAT reactivities of the [(TPA)FeO(X)]+/2+ complexes correlate with the Fe=O and FeO−H stretching vibrations of the reactants and the respective products as determined by infrared photodissociation spectroscopy. Hence, the most reactive [(TPA)FeO(ArIO)]2+ adduct in the series has the weakest Fe=O bond and forms the strongest FeO−H bond in the HAT reaction., The reaction kinetics of H‐atom transfer mediated by iron(IV)oxo complexes with different cis‐ligands can be studied in a modular flow reactor coupled to MS detection. The HAT reactivity correlates with the intrinsic properties of the isolated complexes in the gas phase. A ligand with a larger binding energy forms a more reactive complex for the HAT reactions, has a weaker FeIV=O bond, and forms a stronger FeIIIO−H bond after the HAT reaction.