Supporting Information For Details Research Articles

Achieving High-Performance Molecular Rectification through Fast Screening Alkanethiol Carboxylate-Metal Complexes Electroactive Units

Achieving High-Performance Molecular Rectification through Fast Screening Alkanethiol Carboxylate-Metal Complexes Electroactive Units

Supramolecular Template-Assisted Catalytic [2+2] Photocycloaddition in Homogeneous Solution

Supramolecular Template-Assisted Catalytic [2+2] Photocycloaddition in Homogeneous Solution

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Comment on “Charge Carrier Extraction in Organic Solar Cells Governed by Steady‐State Mobilities”

Comment on “Charge Carrier Extraction in Organic Solar Cells Governed by Steady‐State Mobilities”

A Two-Photon Excitation Based Fluorogenic Probe for Sialome Imaging in Living Systems.

Taking advantage of the fluorescence property of alkyne-modified naphthalimide, the two-photon excited fluorogenic probe Naph-yne is used for azide-tagged mannosyl glycoprotein imaging both at the cellular level and for vertebrate model organisms.

ChemInform Abstract: Catalytic, Enantioselective, and Highly Chemoselective Bromocyclization of Olefinic Dicarbonyl Compounds.

Catalytic enantioselective halocyclization of olefinic substrates attracted much attention over the past few years. The resulting enantioenriched heterocycles form the core of many natural products and pharmaceutically important intermediates. In addition, the halogen atoms can be manipulated readily to give various functional building blocks. Most of the reported catalytic enantioselective halocyclization reactions involve the use of a nitrogenor an oxygen-containing nucleophilic partner that has an N H or a O H moiety (e.g., amides or alcohols/carboxylic acids, respectively). The catalysts can then interact with the R H functionalities (R=N, O) through hydrogen bonds and/or salt bridges. Such interactions allow for an effective enantioinduction, resulting in highly enantioselective transformations. 1,3-Dicarbonyl compounds 1, which contain an acidic proton in a-position to the carbonyl funtionalities, are also potential nucleophiles for halocyclizations (when R is an olefinic side chain), furnishing highly functionalized cyclic ethers 3 (Scheme 1). However, this type of nucleophile is also highly susceptible to halogenation in a-position to the carbonyl functionalities, which is a well-known process. The resulting a-halogenated dicarbonyl compound 2 is not a good halogenating reagent and not usually used in the halocyclization of olefinic substrate 1. Nonetheless, herein we report an efficient, catalytic, and highly enantioselective bromocyclization of olefinic 1,3-dicarbonyl compounds, giving rise to highly functionalized furans (see below). A protocol that employs an amine–thiocarbamate as catalysts was developed for the chemoselective bromination at the olefinic moiety over the carbon atom in a-position to the carbonyl functionalities. At the outset of this study, we screened several catalysts that are commonly used in halocyclizations. Olefinic 1,3dicarbonyl compound 1a and N-bromosuccinimide (NBS) were used as substrate and stoichiometric source of the halogen atom, respectively. Reactions with simple catalysts, including DABCO (4), DBU, and DMAP, gave significant amounts of 2-bromo 1,3-dicarbonyl compound 2a, while the reaction with NEt3 gave a mixture of unidentified products (Table 1, entries 1–4). In particular, when DBU was used as the catalyst, cyclized product 3a was not obtained and 2a was isolated in 98% yield. During further investigations, we found that catalysts with Lewis basic sulfur atoms preferably mediate the bromination at the olefinic moiety instead of at the carbon atom in aposition to the carbonyl functionalities, and thus facilitate the cyclization process. The reaction with triphenylphosphine sulfide (5) gave the desired product 3a with only trace amounts of 2a (Table 1, entry 5). When the reaction was catalyzed by thiocarbamate 6, 3a was obtained as the only product in 78% yield (Table 1, entry 6). To our delight, 3a was obtained in an excellent yield (92%) and with only a negligible amount of 2a when amine–thiocarbamate catalyst 7a was used (Table 1, entry 7). Encouraged by these preliminary results, we proceeded to optimize the reaction conditions and to develop the asymmetric version of the reaction. A systematic screening of various halogen sources and solvents showed that toluene and NBS gave the best results (see the Supporting Information for details). The influence of the reaction temperature was also examined. At 60 8C, the reaction of 1a with quinidine-derived amine–thiocarbamate 7a gave product 3a in 34% yield and 16% ee (Table 2, entry 1, footnote c). The ee value and yield improved when the reaction was conducted at 40 8C (Table 2, entry 1). Unexpectedly, reactions with thiocarbamate catalysts that contain other cinchona alkaloid frameworks, including quinine, cinchonine, and cinchonidine, were sluggish and no Scheme 1. Comparison of previous and present studies.

De Novo Generation of Singlet Oxygen and Ammine Ligands by Photoactivation of a Platinum Anticancer Complex

De Novo Generation of Singlet Oxygen and Ammine Ligands by Photoactivation of a Platinum Anticancer Complex

Catalytic, Enantioselective, and Highly Chemoselective Bromocyclization of Olefinic Dicarbonyl Compounds

Catalytic enantioselective halocyclization of olefinic substrates attracted much attention over the past few years. The resulting enantioenriched heterocycles form the core of many natural products and pharmaceutically important intermediates. In addition, the halogen atoms can be manipulated readily to give various functional building blocks. Most of the reported catalytic enantioselective halocyclization reactions involve the use of a nitrogenor an oxygen-containing nucleophilic partner that has an N H or a O H moiety (e.g., amides or alcohols/carboxylic acids, respectively). The catalysts can then interact with the R H functionalities (R=N, O) through hydrogen bonds and/or salt bridges. Such interactions allow for an effective enantioinduction, resulting in highly enantioselective transformations. 1,3-Dicarbonyl compounds 1, which contain an acidic proton in a-position to the carbonyl funtionalities, are also potential nucleophiles for halocyclizations (when R is an olefinic side chain), furnishing highly functionalized cyclic ethers 3 (Scheme 1). However, this type of nucleophile is also highly susceptible to halogenation in a-position to the carbonyl functionalities, which is a well-known process. The resulting a-halogenated dicarbonyl compound 2 is not a good halogenating reagent and not usually used in the halocyclization of olefinic substrate 1. Nonetheless, herein we report an efficient, catalytic, and highly enantioselective bromocyclization of olefinic 1,3-dicarbonyl compounds, giving rise to highly functionalized furans (see below). A protocol that employs an amine–thiocarbamate as catalysts was developed for the chemoselective bromination at the olefinic moiety over the carbon atom in a-position to the carbonyl functionalities. At the outset of this study, we screened several catalysts that are commonly used in halocyclizations. Olefinic 1,3dicarbonyl compound 1a and N-bromosuccinimide (NBS) were used as substrate and stoichiometric source of the halogen atom, respectively. Reactions with simple catalysts, including DABCO (4), DBU, and DMAP, gave significant amounts of 2-bromo 1,3-dicarbonyl compound 2a, while the reaction with NEt3 gave a mixture of unidentified products (Table 1, entries 1–4). In particular, when DBU was used as the catalyst, cyclized product 3a was not obtained and 2a was isolated in 98% yield. During further investigations, we found that catalysts with Lewis basic sulfur atoms preferably mediate the bromination at the olefinic moiety instead of at the carbon atom in aposition to the carbonyl functionalities, and thus facilitate the cyclization process. The reaction with triphenylphosphine sulfide (5) gave the desired product 3a with only trace amounts of 2a (Table 1, entry 5). When the reaction was catalyzed by thiocarbamate 6, 3a was obtained as the only product in 78% yield (Table 1, entry 6). To our delight, 3a was obtained in an excellent yield (92%) and with only a negligible amount of 2a when amine–thiocarbamate catalyst 7a was used (Table 1, entry 7). Encouraged by these preliminary results, we proceeded to optimize the reaction conditions and to develop the asymmetric version of the reaction. A systematic screening of various halogen sources and solvents showed that toluene and NBS gave the best results (see the Supporting Information for details). The influence of the reaction temperature was also examined. At 60 8C, the reaction of 1a with quinidine-derived amine–thiocarbamate 7a gave product 3a in 34% yield and 16% ee (Table 2, entry 1, footnote c). The ee value and yield improved when the reaction was conducted at 40 8C (Table 2, entry 1). Unexpectedly, reactions with thiocarbamate catalysts that contain other cinchona alkaloid frameworks, including quinine, cinchonine, and cinchonidine, were sluggish and no Scheme 1. Comparison of previous and present studies.

Reduction of Quinones by NADH Catalyzed by Organoiridium Complexes

Reduction of Quinones by NADH Catalyzed by Organoiridium Complexes

Use of Metadynamics in the Design of isoDGR-Based αvβ3 Antagonists To Fine-Tune the Conformational Ensemble

The integrin family of cell-adhesion receptors regulates cellular functions crucial to the initiation, progression, and metastasis of solid tumors. In particular, integrin avb3 plays a key role in endothelial cell survival and migration during tumor angiogenesis. It is therefore gaining increasing importance as a drug target in antiangiogenic cancer therapy. The sequence Arg-Gly-Asp (RGD), which is contained in natural avb3 interactors, such as vitronectin, fibronectin, fibrinogen, osteopontin, and tenascin, is by far the most prominent ligand to promote specific cell adhesion through stimulation. This sequence is therefore attractive as a lead for the development of different integrin antagonists. Recent biochemical studies showed that deamidation of the NGR sequence gives rise to isoDGR, a new avb3-binding motif. This sequence constitutes a novel class of peptidic integrin ligands and paves the way to drug-design studies with a focus on the synthesis and characterization of a new generation of isoDGR-based macrocycles. For the design of low-molecular-mass isoDGR-containing molecules, an accurate determination of their biologically active conformation is a prerequisite. The presence of the b bond induces high flexibility in isoDGR-containing macrocycles and thus augments the range of accessible interconverting conformations. However, the identification of relevant conformations that might affect binding affinity is challenging for standard spectroscopic and diffraction techniques. Atomistic simulations, such as molecular dynamics (MD), replica-exchange molecular dynamics (REMD), and Monte Carlo (MC) simulations, can complement experimental data. However, they often fail to generate reliable equilibrium conformations because of the rugged and complex nature of the free-energy surface (FES) that is accessible to the system. As a consequence, computational sampling is often relegated to some local, unrealistic minima, which compromise subsequent docking studies. As computational drug design becomes increasingly reliant on virtual screening and on high-throughput 3D modeling, the need for fast and accurate computational methods for sampling of the ensemble of energetically accessible conformations is warranted. In this context, several techniques, including the local-elevation method, taboo search, the Wang–Landau method, adaptive force bias, conformational flooding, umbrella sampling, weighted histogram techniques, transitionstate theory, and path sampling, have been developed to address the sampling problem, through either reconstruction of the free energy or the direct acceleration of events that might happen on a long timescale (“rare events”). Related to these methods, metadynamics (MetaD) has emerged as a powerful coarse-grained non-Markovian molecular-dynamics approach for the acceleration of rare events and the efficient and rapid computation of multidimensional free-energy surfaces as a function of a restricted number of degrees of freedom, named collective variables (CVs). If the CVs are appropriately chosen for the system under investigation, MetaD directly provides a good estimate of the free energy of the system projected into the CVs (see the Supporting Information for details). Notably, the free energy is not immediately deducible by other sampling methods, such as umbrella sampling, in which the free-energy profile is not obtained directly from the simulations and requires an additional computational step, such as the weighted histogram analysis method (WHAM). In this study, we developed a protocol based on the combination of MetaD and docking simulations to analyze the conformations and the avb3-binding properties of isoDGR-containing cyclopeptides and to predict the conformational effects of chemical modifications and discriminate binders from nonbinders in silico. To investigate the conformational equilibrium of RGD-, DGR-, and isoDGRcontaining cyclopeptides (cyclization mode involving cysteine side chains) and to exhaustively explore their FESs, we performed well-temperedMetaD simulations, for which we chose Gly f and y angles as CVs (Figure 1; for simulation details, see the Supporting Information). As it lacks a side chain, Gly has large conformational freedom around its backbone dihedral angles. Therefore, Gly can explore a considerably larger area in the Ramachandran energy diagram than any other amino acid, and occupies five [*] Dr. A. Spitaleri, Dr. M. Ghitti, Dr. S. Mari, Dr. G. Musco Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Center of Genomic and Bioinformatics S. Raffaele Scientific Institute via Olgettina 58, 20132 Milan (Italy) Fax: (+39)02-2643-4153 E-mail: giovanna.musco@hsr.it

Unifying Concepts in Catalysis

Unifying Concepts in Catalysis

Nanoscale Flexibility Parameters of Alzheimer Amyloid Fibrils Determined by Electron Cryo‐Microscopy

Nanoscale Flexibility Parameters of Alzheimer Amyloid Fibrils Determined by Electron Cryo‐Microscopy

Chemical Reactions within Single-Walled Carbon Nanotube Channels

Modification of single-walled carbon nanotube (SWNT) channels by intercalation of semiconductor crystals leads to a change of the electronic structure of nanotubes, as was observed by Raman spectroscopy of CdI2@SWNT and CdS@SWNT composites (see the Supporting Information for details). The composites exhibit the upward shift of RBM and G vibrational frequencies as compared to raw SWNTs, which is attributed to depletion of electrons from the SWNT walls to the intercalated compound