α-ω Alkenyl-bis-S-Guanidine Thiourea Dihydrobromide Affects HeLa Cell Growth Hampering Tubulin Polymerization

Active and specific: The newly synthesized compound 8 (nonane-1,9-diyl-bis-S-amidinothiourea dihydrobromide) affects HeLa cell growth by targeting tubulin polymerization and inducing Parp-1 cleavage and cytochrome c release from mitochondria, the hallmarks of the intrinsic apoptotic pathway.

[Full Papers]

Dr. Jessica Ceramella, Dr. Annaluisa Mariconda, Dr. Camillo Rosano, Dr. Domenico Iacopetta, Dr. Anna Caruso, Prof. Pasquale Longo, Prof. Maria Stefania Sinicropi, Prof. Carmela Saturnino

doi.org/10.1002/cmdc.202000544

Zinc Interactions with a Soluble Mutated Rat Amylin to Mimic Whole Human Amylin: An Experimental and Simulation Approach to Understand Stoichiometry, Speciation and Coordination of the Metal Complexes

Stoichiometry, speciation and coordination features of zinc(II) complexes with islet amyloid polypeptide (IAPPS) were unveiled by a combined ESI-MS, potentiometric and NMR study. Mononuclear species start to form around pH 6; Zn2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18 H). NMR and DFT findings confirm the binding and stress the role of noncovalent interactions in the metal complexes.

[Full Papers]

Dr. Antonio Magrì, Dr. Giovanni Tabbì, Dr. Giuseppe Di Natale, Prof. Diego La Mendola, Dr. Adriana Pietropaolo, Prof. Maria Antonietta Zoroddu, Dr. Massimiliano Peana, Prof. Enrico Rizzarelli

doi.org/10.1002/chem.202002114

Dual Improvement of β-MnO2 Oxygen Evolution Electrocatalysts via Combined Substrate Control and Surface Engineering

β-MnO2 nanostructures, eventually decorated with Co3O4 or Fe2O3 nanoparticles, are grown by a plasma-assisted strategy on conductive glasses and porous Ni foams, and investigated as catalysts for the oxygen evolution reaction. The combined control over substrate properties and β-MnO2 surface decoration yields outstanding functional performances, paving the way to real-world applications in sustainable energy conversion processes.

[Full Papers]

Dr. Lorenzo Bigiani, Prof. Alberto Gasparotto, Prof. Chiara Maccato, Prof. Cinzia Sada, Prof. Johan Verbeeck, Dr. Teresa Andreu, Prof. Juan Ramón Morante, Dr. Davide Barreca

doi.org/10.1002/cctc.202000999

Sustainability and Chaos in the Abiotic Polymerization of 3′,5′ Cyclic Guanosine Monophosphate: The Role of Aggregation

Glued by guanines: In this work, we show that the unique aggregation properties of H-form 3′,5′ cyclic guanosine monophosphate molecules enable the sustainable non-enzymatic template-free synthesis of oligonucleotide sequences from nucleotide precursors on timescales of several days even in the presence of water.

[Full Papers]

Dr. Giovanna Costanzo, Dr. Judit E. Šponer, Prof. Jiří Šponer, Dr. Angela Cirigliano, Prof. Piero Benedetti, Dr. Valeria Giliberti, Dr. Raffaella Polito, Prof. Ernesto Di Mauro

doi.org/10.1002/syst.202000011

Chemo-Enzymatic Synthesis of S. mansoni O-Glycans and Their Evaluation as Ligands for C-Type Lectin Receptors MGL, DC-SIGN, and DC-SIGNR

A series of parasite O-glycans structures have been prepared by chemoenzymatic synthesis and their affinity towards several C-type lectins screened using glycan arrays.

[Full Papers]

Dr. Julie Pham, Dr. Alvaro Hernandez, Dr. Anna Cioce, Dr. Silvia Achilli, Dr. Giulio Goti, Dr. Corinne Vivès, Dr. Michel Thepaut, Prof. Dr. Anna Bernardi, Prof. Dr. Franck Fieschi, Dr. Niels-Christian Reichardt

doi.org/10.1002/chem.202000291

A Visible-Light-Powered Polymerization Method for the Immobilization of Enantioselective Organocatalysts into Microreactors

Let the light do the work! A universal protocol for the immobilization of enantioselective organocatalysts in glass microreactors was developed. By using the power of visible light, a Hayashi-Jørgensen catalyst was exemplarily incorporated into a polystyrene-based monolithic structure and used for asymmetric transformations in flow (see graphic).

[Communications]

Rico Warias, Dr. Daniele Ragno, Prof. Alessandro Massi, Prof. Detlev Belder

doi.org/10.1002/chem.202002063

Additive Manufacturing of Aqueous-Processed LiMn2O4 Thick Electrodes for High-Energy-Density Lithium-Ion Batteries

The Cover Feature illustrates 3D-printed cathode based on LiMn2O4 (LMO) as active material, which are fabricated by robocasting AM via aqueous processing. Such innovative technology is environmentally friendly, fast, and easily scalable. More information can be found in the Article by E. Quartarone and co-workers.

[Cover Pictures]

Lorenzo Airoldi, Umberto Anselmi-Tamburini, Barbara Vigani, Silvia Rossi, Piercarlo Mustarelli, Dr. Eliana Quartarone

doi.org/10.1002/batt.202000208

Activating Effect of 3-Benzylidene Oxindoles on AMPK: From Computer Simulation to High-Content Screening

Content counts: The binding site of 3-benzylidene oxindoles within the kinase domain of AMP-activated protein kinase (AMPK) was established by correlating calculated and experimental activities. Such binding to the kinase domain leads to AMPK activation. A cell model based on the FRET effect was used under HCS conditions to evaluate target activity.

[Full Papers]

Daria S. Novikova, Dr. Tatyana A. Grigoreva, Dr. Gleb S. Ivanov, Prof. Dr. Gerry Melino, Prof. Dr. Nickolai A. Barlev, Dr. Vyacheslav G. Tribulovich

doi.org/10.1002/cmdc.202000579

Highly Nickel-Loaded γ-Alumina Composites for a Radiofrequency-Heated, Low-Temperature CO2 Methanation Scheme

Multifunction composites: We propose a low-temperature radiofrequency-heated CO2 methanation scheme based on highly Ni-loaded γ-Al2O3 composites. These composites act as electrically conductive/magnetic susceptors for the induction heating technology while serving as robust catalysts for low-temperature CO2 methanation.

[Full Papers]

Dr. Wei Wang, Dr. Cuong Duong-Viet, Dr. Giulia Tuci, Prof. Yuefeng Liu, Dr. Andrea Rossin, Dr. Lapo Luconi, Dr. Jean-Mario Nhut, Prof. Lam Nguyen-Dinh, Dr. Giuliano Giambastiani, Dr. Cuong Pham-Huu

doi.org/10.1002/cssc.202001885

Synthesis, Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

Selective sulfonamides: A squalene scaffold bearing sulfonamide moieties showed potent inhibitory action against the human carbonic anhydrase (CA) II. These compounds proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms, thereby proving interesting candidates for preclinical evaluation in glaucoma or various diseases in which the enzyme is involved.

[Full Papers]

Dr. Lilia Clima, Bogdan Florin Craciun, Dr. Andrea Angeli, Andrea Petreni, Alessandro Bonardi, Dr. Alessio Nocentini, Dr. Fabrizio Carta, Prof. Paola Gratteri, Prof. Mariana Pinteala, Prof. Claudiu T. Supuran

doi.org/10.1002/cmdc.202000500

Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells

As keen as mustard: Aromatic 3-chloropiperidines designed to improve the therapeutic potential of mustard-based DNA alkylating agents have been synthesized and evaluated. These small molecules exhibited a marked anti-proliferative effect preferentially against BxPC-3 pancreatic adenocarcinoma cells in 2D and 3D cultures, thus demonstrating themselves to be promising candidates for the further development of sustainable chemotherapeutics active against pancreatic tumors.

[Full Papers]

Tim Helbing, Caterina Carraro, Alexander Francke, Dr. Alice Sosic, Michele De Franco, Prof. Dr. Valentina Gandin, Prof. Dr. Richard Göttlich, Prof. Dr. Barbara Gatto

doi.org/10.1002/cmdc.202000457

Recent Advancement in the Search of Innovative Antiprotozoal Agents Targeting Trypanothione Metabolism

Targeting the trypanothione: Owing to its critical role played in all trypanosomatids and its absence from human hosts, the trypanothione pathway offers prominent opportunities to develop innovative antiprotozoal agents. Recent efforts devoted to the search for inhibitors that target the key enzymes trypanothione reductase and trypanothione synthetase-amidase are discussed.

[Reviews]

Dr. Francesco Saccoliti, Prof. Roberto Di Santo, Prof. Roberta Costi

doi.org/10.1002/cmdc.202000325

Enhancing N2 Fixation Activity by Converting Ti3C2 MXenes Nanosheets to Nanoribbons

Show your beauty: MXenes with two-dimensional (2D) structure have been indicated as promising materials for N2 electrocatalytic conversion to NH3. The transformation of Ti3C2 MXenes from 2D-like nanosheets to 3D-like nanoribbons could enhance significantly the formation of exposed Ti−OH sites to present a superior NH3 formation rate.

[Communications]

Dr. Hua Wei, Dr. Qian Jiang, Prof. Claudio Ampelli, Dr. Shiming Chen, Prof. Siglinda Perathoner, Prof. Yuefeng Liu, Prof. Gabriele Centi

doi.org/10.1002/cssc.202001719

Accurate Modelling of Group Electrostatic Potential and Distributed Polarizability in Dipeptides

Electric properties of biomolecules from building blocks: The atomic or functional-group electrostatic potential and distributed polarizability in dipeptides help to predict the electric properties of bio-macromolecules from their structural subunits. By focusing on the peptide bond, the model takes advantage of a simple and transferable scheme to gain insight on how amino acid residuals ensemble to create proteins.

[Articles]

Angelika Jabłuszewska, Dr. Anna Krawczuk, Prof. Leonardo H. R. Dos Santos, Prof. Piero Macchi

doi.org/10.1002/cphc.202000441

Uncommon overoxidative catalytic activity in a new halo-tolerant alcohol dehydrogenase

Enzymatic catalysis: An unusual alcohol dehydrogenase has been identified from the halo-adapted bacterium H. elongata. HeADH-II shows a great stability to polar solvents and high salt concentration as well as uncommon characteristics such as the lack of enantiopreference and the capability of overoxidizing alcohols to carboxylic acids. To increase the process yields and allowing cofactor recycling, HeADH-II was coupled with a NADH-oxidase from L. pentosus (LpNOX).

[Full Papers]

Dr. Martina L. Contente, Noemi Fiore, Pietro Cannazza, Dr. David Roura Padrosa, Prof. Francesco Molinari, Dr. Louise Gourlay, Prof. Francesca Paradisi

doi.org/10.1002/cctc.202001112

Optimizing Enzymatic Photo-Redox Cycles by a Hybrid Protein Complex Chain

A good combination: We demonstrate how a more efficient photo-redox hybrid protein chain can be assembled by coupling membrane protein complexes from different organisms: bacteria and mammalian cells. This system, assembled in the form of an amphiphilic aggregate suspension, can be further optimized by adapting the protein levels, reaching 90 % of the enzymatic photo-redox efficiency.

[Communications]

Dr. Emiliano Altamura, Paola Albanese, Dr. Francesco Milano, Dr. Livia Giotta, Dr. Massimo Trotta, Dr. Anna Ferretta, Prof. Tiziana Cocco, Prof. Fabio Mavelli

doi.org/10.1002/cptc.202000176

Photophysical Properties of 4-Dicyanomethylene-2-methyl-6-(p-dimethylamino-styryl)-4H-pyran Revisited: Fluorescence versus Photoisomerization

Environmentally sensitive: The fluorescence and photoisomerization of a DCM derivative have been characterized. The fluorescence of the E isomer was strongly sensitive to the solvent, in terms of emission wavelength, quantum yield, and decay time. The compound can photoisomerize, but the Z isomer is not emissive. Such environment-sensitive features are attractive for a large variety of applications as sensors.

[Full Papers]

Dr. Lorenzo Casimiro, Dr. Stéphane Maisonneuve, Dr. Pascal Retailleau, Dr. Serena Silvi, Prof. Juan Xie, Dr. Rémi Métivier

doi.org/10.1002/chem.202002828

Targeting Endocannabinoid Metabolism: an Arrow with Multiple Tips Against Multiple Sclerosis

Endocannabinoids and MS: This review offers a special focus on the modulation of the endogenous levels of endocannabinoids as a novel treatment option for multiple sclerosis. An overview on endocannabinoid metabolism modulators and their in vivo effects on relevant animal models is provided. This paper also highlights key molecular underpinnings of their therapeutic efficacy and critically discusses the potential to turn them into robust clinical candidates.

[Reviews]

Dr. Samuele Maramai, Prof. Margherita Brindisi

doi.org/10.1002/cmdc.202000310

Thermally Regenerable Redox Flow Battery

Burn, bromine, burn: Thermal regenerable redox-flow batteries (TRBs) based on the LiBr/Br2 couple is a promising redox flow cell able to produce energy at the expenses of the salinity gradient of two LiBr water solutions. Restoring the exhausted solution by means of vacuum distillation, TRBs harvest low-temperature heat sources (below 100 °C). The system reaches a high power density and the heat-to-electricity efficiency of the TRB here proposed is around 4 %, the highest value reached in this field so far.

[Full Papers]

Irene Facchinetti, Dr. Elkid Cobani, Dr. Doriano Brogioli, Prof. Fabio La Mantia, Prof. Riccardo Ruffo

doi.org/10.1002/cssc.202001799

Bypassing the Inertness of Aziridine/CO2 Systems to Access 5-Aryl-2-Oxazolidinones: Catalyst-Free Synthesis Under Ambient Conditions

In with the new: The largely investigated catalytic process affording 5-aryl-2-oxazolidinones by the two-step assembly of a C2 precursor with primary amine and carbon dioxide is replaced by the catalyst-free, direct addition of the amine/CO2 adduct to the C2 unit in isopropanol or water.

[Full Papers]

Dr. Giulio Bresciani, Emanuele Antico, Prof. Gianluca Ciancaleoni, Prof. Stefano Zacchini, Prof. Guido Pampaloni, Prof. Fabio Marchetti

doi.org/10.1002/cssc.202001823

Synthesis of 2-alkenylidene-3-oxoindolines: cascade reactions of 4H-furo [3,2-b]indoles with diazoacetates catalyzed by a Cu(I) macrocyclic pyridine-containing ligand (PcL) complex

Cu catalysis: We reported a new and highly selective synthesis of 2-(penta-2,4-dien-1-ylidene) 3-oxoindolines by copper(I)-catalyzed reaction between 4H-furo[3,2-b]indoles and diazoalkanes. This reaction is characterized by a wide functional group tolerance on both reagents giving rise to excellent yield of desired products. In addition, two of these products present good results in second-order nonlinear optical studies.

[Full Papers]

Dr. Valentina Pirovano, Prof. Alessandro Caselli, Alessia Colombo, Prof. Claudia Dragonetti, Matteo Giannangeli, Prof. Elisabetta Rossi, Elisa Brambilla

doi.org/10.1002/cctc.202000887

Water-Soluble Organotin Compounds - Syntheses, Structures and Reactivity towards Fluoride Anions in Water

Defluorination of water is achieved by a simple organoammonium-functionalized diorganotin salt that can easily be synthesized. The latter can easily be regenerated making the whole concept attractive for practical application. DFT calculations support the preferred binding of fluoride anion by the diorganotin salt over the other halide anions.

[Full Papers]

Nour Alashkar, Dr. Massimiliano Arca, Hazem Alnasr, Michael Lutter, Prof. Dr. Vito Lippolis, Klaus Jurkschat

doi.org/10.1002/ejic.202000665

[1]Benzothieno[3,2-b][1]benzothiophene-Phthalocyanine Derivatives: A Subclass of Solution-Processable Electron-Rich Hole Transport Materials

The Cover Feature shows the tetrasubstituted phthalocyanine (Pc)-benzothienobenzothiophene (BTBT) structure as an element of the geometric pattern of an azulejos mosaic. The presence of distinct Pc and BTBT tiles suggests that both the building blocks are synthesized separately and coupled in the last stage of the synthetic pathway. Furthermore the high planarity of the molecule, confirmed by DFT calculations, is visually highlighted. More information can be found in the Full Paper by G. Zanotti et al.

[Cover Pictures]

Dr. Gloria Zanotti, Dr. Nicola Angelini, Dr. Giuseppe Mattioli, Dr. Anna Maria Paoletti, Dr. Giovanna Pennesi, Dr. Daniela Caschera, Dr. Anatoly Petrovich Sobolev, Prof. Luca Beverina, Adiel Mauro Calascibetta, Dr. Alessandro Sanzone, Prof. Aldo Di Carlo, Dr. Beatrice Berionni Berna, Dr. Sara Pescetelli, Dr. Antonio Agresti

doi.org/10.1002/cplu.202000566

Microfluidic Visible-Light Paternò-Büchi Reaction of Oxindole Enol Ethers

From oxindole with flow: Oxindole enol ethers are engaged in microfluidic visible-light Paternò-Büchi processes, allowing the concomitant C2-C3 functionalisation of the biorelevant heterocyclic core, in high yield and selectivity.

[Communications]

Pietro Franceschi, Javier Mateos, Dr. Alberto Vega-Peñaloza, Dr. Luca Dell'Amico

doi.org/10.1002/ejoc.202001057

Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor

Holding on to everything: A3 adenosine receptor ligands conjugated to Fe-filled carbon nanotubes were developed to target specific cancer cell lines for cancer magnetic cell sorting and thermal therapy. The nanostructure was able to efficiently bind to the A3 adenosine receptors, unfortunately, when interfaced with cells, the conjugates did not displayed selectivity for those overexpressing the receptor.

[Full Papers]

Dr. Florent Pineux, Dr. Stephanie Federico, Prof. Karl-Norbert Klotz, Sonja Kachler, Dr. Carine Michiels, Dr. Mattia Sturlese, Prof. Maurizio Prato, Prof. Giampiero Spalluto, Prof. Stefano Moro, Davide Bonifazi

doi.org/10.1002/cmdc.202000466

Organocatalytic Reduction of Nitroarenes with Phenyl(2-quinolyl)methanol

Transition metal free reductions of nitroarenes with phenyl(2-quinolyl)methanol (PQM) as organocatalyst have been performed applying NaBH4 or NaCNBH3 as stoichiometric reducing agent. The NO2 group reduction is highly chemoselective giving the corresponding anilines (17-91 % yields). The use of substoichiometric amounts of PQM allows more sustainable processes: reaction products are easily isolated and PQM can be directly recovered and recycled.

[Full Papers]

Prof. Dr. Donatella Giomi, Dr. Jacopo Ceccarelli, Prof. Dr. Antonella Salvini, Prof. Dr. Alberto Brandi

doi.org/10.1002/slct.202003234

Targeted Small-Molecule Conjugates: The Future is Now

One target, more options. The toolbox of high-affinity ligands for clinically relevant proteins is continuously expanding. Covalent conjugates of these ligands with drugs, radiotracers and other bioactive agents are being studied for therapy and imaging. The pharmacokinetic properties, chemical accessibility and versatility are just a few examples of the positive features that could bring targeted small molecule conjugates to a leading role in future medicine.

[Viewpoints]

Dr. Alberto Dal Corso

doi.org/10.1002/cbic.202000507

195Pt and 15N NMR Data in Square Planar Platinum(II) Complexes of the Type [Pt(NH3)aXb]n (Xb = Combination of Halides): “NMR Effective Molecular Radius” of Coordinated Ammonia

In the model [Pt(NH3)3X]+ (X = Cl, Br, I) complex the red torus and arrows represent the electric pseudo-ring currents and the induced magnetic field, respectively, generated by an applied B° magnetic field. The considered Pt and cis to X N-donors are indicated in red instead the trans is in blue. Different colors represent opposite NMR chemical shift variations (195Pt and 15N) observed when the X ligand both ionic radius and trans-influence are varied. In this work, such considerations are extended to the general case of PtII complexes with X and NH3 ligands.

[Full Papers]

Prof. Michele Benedetti, Dr. Federica De Castro, Prof. Paride Papadia, Dr. Daniela Antonucci, Prof. Francesco P. Fanizzi

doi.org/10.1002/ejic.202000474

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

Finding hits for the Spike: Our computational studies on SARS-CoV-2 Spike protein receptor binding domain identified the N-terminal region as a potential druggable hot-spot. Herein, docking and pharmacophore HTS yielded a set of consensus molecules suitable for drug discovery screening. These compounds could represent lead molecules able to modulate the Spike-ACE2 protein-protein interaction, a putative intervention mark to discover therapeutics against SARS-CoV-2 pandemic.

[Full Papers]

Maria Rita Gulotta, Jessica Lombino, Dr. Ugo Perricone, Giada De Simone, Nedra Mekni, Dr. Maria De Rosa, Prof. Patrizia Diana, Dr. Alessandro Padova

doi.org/10.1002/cmdc.202000259

Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multitarget Ligands Directed towards Relevant Alzheimer's Targets

On target(s): Different 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-ones have been synthesized and tested for their activity towards specific enzymes (AChE, BChE, MAO A and B) and targets (aggregation of Aβ and ROS production) related to Alzheimer's disease. Some compounds showed balanced multitargeting inhibitory effect, but one was a potent and selective human MAO B inhibitor with a neuroprotectant profile against Aβ1-42 and H2O2.

[Full Papers]

Dr. Rosa Purgatorio, Dr. Larisa N. Kulikova, Dr. Leonardo Pisani, Dr. Marco Catto, Dr. Modesto de Candia, Prof. Antonio Carrieri, Prof. Saverio Cellamare, Dr. Annalisa De Palma, Andrey A. Beloglazkin, Ghulam Reza Raesi, Prof. Leonid G. Voskressensky, Prof. Cosimo D. Altomare

doi.org/10.1002/cmdc.202000468

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

What a sweet metallic taste! Metabolic changes in tumor cells cause an increase of glucose uptake and consumption. So far, metal complexes have been widely used both as probes for tumor imaging and as chemotherapeutic agents. Therefore, the combination of sugar portions with metal complexes generates conjugated compounds with potential diagnostic and therapeutic applications in cancer.

[Reviews]

Giulia Bononi, Dalila Iacopini, Gaspare Cicio, Dr. Sebastiano Di Pietro, Prof. Carlotta Granchi, Prof. Valeria Di Bussolo, Prof. Filippo Minutolo

doi.org/10.1002/cmdc.202000456

The European Federation for Medicinal Chemistry (EFMC) Best Practice Initiative: Validating Chemical Probes

What are chemical probes and why are they important? Chemical probes are designed to selectively address a biological question; this is distinctly different from a drug, which is designed to produce a clinical outcome! Simple guidelines can be used to generate high-quality chemical probes and obtain reliable data to further our understanding of human biology and disease.

[Viewpoints]

Dr. Jean Quancard, Prof. Brian Cox, Dr. Dirk Finsinger, Dr. Stéphanie M. Guéret, Dr. Ingo V. Hartung, Dr. Hannes F. Koolman, Dr. Josef Messinger, Prof. Dr. Gianluca Sbardella, Prof. Dr. Stefan Laufer

doi.org/10.1002/cmdc.202000597

Synthesis of Distally-Bridged Chiral Resorcinarene Crowns

The synthesis and characterisation of twelve novel distally-bridged chiral resorcinarene crowns is presented. The fascinating architecture of these partially-enclosed chiral basket molecules is evident in the structures which have been determined by single-crystal X-ray crystallography. This work enables further exploration of these enantio-pure chiral baskets as possible chiral resolving agents.

[Full Papers]

Dr. Daniel A. Tan, Dr. Chiara Massera, Dr. Matthew J. McIldowie, Dr. Mauro Mocerino

doi.org/10.1002/ejoc.202000874

Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents

We report hybrids of pyrazoline and pyrrolidine-2,5-dione as antitumor agents with oral bioavailability and efficacy toward tumor regression. One compound in particular was found to have antiproliferative effects toward HT29, MCF7, and K562 cell lines in the sub-micromolar range. It was also found to cause in vivo tumor regression by intraperitoneal and oral administration in HT29 xenograft models. It also exhibited dose-dependent inhibition of the anti-apoptotic protein Bcl-2 and these biological assay data corelated well with docking studies.

[Full Papers]

Kalpana Tilekar, Neha Upadhyay, Prof. Franz-Josef Meyer-Almes, Dr. Fulvio Loiodice, Natalia Y. Anisimova, Tatiana S. Spirina, Darina V. Sokolova, Galina B. Smirnova, Dr. Jun-yong Choe, Dr. Vadim S. Pokrovsky, Prof. Antonio Lavecchia, Prof. C S Ramaa

doi.org/10.1002/cmdc.202000458

Potency and Selectivity Optimization of Tryptophanol-Derived Oxazoloisoindolinones: Novel p53 Activators in Human Colorectal Cancer

Hunting p53 activators: Hit-to-lead optimization of the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 led to the development of a chemical library of 34 enantiomerically pure analogues. The compounds were screened in cancer and normal colon cells. From this screening, emerged a novel (R)-tryptophanol derivative with increased in vitro potency and selectivity in p53 expressing HCT116 cells compared with SLMP53-1.

[Full Papers]

Valentina Barcherini, Joana Almeida, Elizabeth A. Lopes, Dr. Mi Wang, Diogo Magalhães e Silva, Dr. Mattia Mori, Dr. Shaomeng Wang, Dr. Lucília Saraiva, Dr. Maria M. M. Santos

doi.org/10.1002/cmdc.202000522

Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy

Strike! Starting from a proposed drug combination of idebenone and donepezil, we rationally designed and synthesized a small library of highly merged donepezil-based multi-target-directed ligands (MTDLs), obtained by indanone bioisosteric substitution. The new MTDL 9 has been shown to hit Alzheimer's disease by cholinesterase inhibition, together with Aβ and oxidative pathway modulation.

[Full Papers]

Dr. Rosaria Perone, Claudia Albertini, Dr. Elisa Uliassi, Flaminia Di Pietri, Pedro de Sena Murteira Pinheiro, Dr. Sabrina Petralla, Nicola Rizzardi, Prof. Romana Fato, Dr. Lenka Pulkrabkova, Dr. Ondrej Soukup, Dr. Anna Tramarin, Prof. Manuela Bartolini, Prof. Maria Laura Bolognesi

doi.org/10.1002/cmdc.202000484

Shining Light on TiIV Complexes: Exceptional Tools for Metallaphotoredox Catalysis

Metallaphotoredox catalysis is emerging as an excellent and versatile cornerstone for the development of modern synthetic methodologies. Recent examples have displayed how the redox chemistry of titanium-based complexes can be triggered by organic and inorganic chromophores in catalytic processes activated by visible-light, affording synthetically demanding products.

[Minireview]

Dr. Andrea Fermi, Dr. Andrea Gualandi, Dr. Giacomo Bergamini, Dr. Pier Giorgio Cozzi

doi.org/10.1002/ejoc.202000966

Construction of a Functionalized Selenophene-Allylidene Ligand via Alkyne Double Action at a Diiron Complex

C3 to C7 chain elongation unexpectedly occurs on the {Fe2Cp2(CO)2} scaffold by the one pot reaction of a selenium-functionalized vinyliminium ligand with two alkyne molecules, enabled by steric factors and affording an unprecedented µ-allylidene ligand derivatized with a 3-amino-selenophene ring.

[Full Papers]

Dr. Alice De Palo, Dr. Stefano Zacchini, Dr. Guido Pampaloni, Dr. Fabio Marchetti

doi.org/10.1002/ejic.202000371

Effects of Photosensitizers and Reaction Media on Light-Driven Water Oxidation with Trinuclear Ruthenium Macrocycles

Matter of Choice: Several factors including choice of photosensitizer and reaction media have a strong impact on the efficiency of photocatalytic water oxidation with macrocyclic ruthenium complexes.

[Articles]

Ana-Lucia Meza-Chincha, Dorothee Schindler, Prof. Dr. Mirco Natali, Prof. Dr. Frank Würthner

doi.org/10.1002/cptc.202000133

Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides

The Cover Feature shows an unprecedented generation of highly polarized lithium phosphides (LiPR2) through direct selective deprotonation of secondary phosphines (HPR2) in the biodegradable choline chloride/glycerol eutectic mixture, at ambient temperature and under aerobic conditions, and their chemoselective addition to aldehydes or epoxides. More information can be found in the Full Paper by L. Cicco et al.

[Cover Pictures]

Dr. Luciana Cicco, Alba Fombona-Pascual, Alba Sánchez-Condado, Prof. Gabino A. Carriedo, Prof. Filippo M. Perna, Prof. Vito Capriati, Prof. Alejandro Presa Soto, Prof. Joaquín García-Álvarez

doi.org/10.1002/cssc.202001869

Metal and Oxidant Free Construction of Substituted- and/or Polycyclic Indoles: A Useful Alternative to Bischler and Related Syntheses

A wide range of substituted indoles, including complex polycyclic-architectures were easily assembled by means of a Amberlyst 15H catalyzed synthesis that employs 1,2-diaza-1,3-dienes and anilines. The metal and oxidant free methodology proposed here is characterized by good yields, total and predictable regioselectivity, and the ability to provide electron withdrawing substituted indoles.

[Full Papers]

Dr. Giacomo Mari, Dr. Lucia De Crescentini, Prof. Gianfranco Favi, Dr. Stefania Santeusanio, Prof. Fabio Mantellini

doi.org/10.1002/ejoc.202000845

Ionic-Liquid Controlled Nitration of Double Bond: Highly Selective Synthesis of Nitrostyrenes and Benzonitriles

The conversion of aryl alkenes into β-nitrostyrenes or benzonitriles with NaNO2 can be governed by an appropriate choice of ionic liquid medium. A general trend was found for the selectivity of these processes, which depends on the nature of IL, with imidazolium-based ILs, such as [Bmim] Cl, that favor the formation of β-nitrostyrenes, while tetraalkylammonium-based ILs, such as TBAA, that favor the formation of benzonitriles.

[Full Papers]

Dr. Michele Casiello, Dr. Daniela Caputo, Dr. Caterina Fusco, Dr. Pietro Cotugno, Dr. Vito Rizzi, Prof. Maria Michela Dell'Anna, Prof. Lucia D'Accolti, Prof. Angelo Nacci

doi.org/10.1002/ejoc.202001027

The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues

Triazole, the magic ring: We have extended the structure-activity relationships of substituted 1,2,4-triazole derivatives to determine in vitro inhibitory and fungicidal activity. The antifungal activity of this class of compounds is greatly dependent upon the substitution on one of the aromatic rings. Multiple linear regression analysis revealed three critical descriptors that contribute to the activity.

[Full Papers]

Prof. Grigoris Zoidis, Dr. Eftichia Kritsi, Dr. Paulina Lecinska, Dr. Marija Ivanov, Dr. Panagiotis Zoumpoulakis, Dr. Marina Sokovic, Dr. Marco Catto

doi.org/10.1002/cmdc.202000312

Dichalcogenides/Oxone®-Mediated Cyclization of (Z)-Chalcogenoenynes under Ultrasound Irradiation

The system containing Oxone® as an oxidant under ultrasound irradiation conditions was used to access a series of 3-chalcogenyl chalcogenophenes in short reaction time. This is a green and eco-friendly protocol for the electrophilic cyclization of (Z)-thio-, (Z)-seleno- and (Z)-telluroenynes in the presence of diselenide or ditelluride/Oxone® system, furnishing 3-functionalized thiophenes, selenophenes and tellurophenes, respectively, from 28 % to 87 % yield.

[Full Papers]

Dr. Liane K. Soares, Dr. Angelita M. Barcellos, Dr. José S. S. Neto, Prof. Dr. Diego Alves, Prof. Dr. Eder J. Lenardão, Prof. Dr. Ornelio Rosati, Prof. Dr. Claudio Santi, Prof. Dr. Gelson Perin

doi.org/10.1002/slct.202002252

Front Cover: Hydrolytic Nanozymes (Eur. J. Org. Chem. 32/2020)

The Front Cover shows the “Prato della Valle” square in Padova. Designed in 1775 by Andrea Memmo, with its >88,000 m2 and 88 statues, it is one of the biggest squares in Europe. The perfect geometry resembles that of a supramolecular structure, the core of the research reported in this minireview. On the top, is the computer-simulated interaction of a gold nanoparticle with DNA, that leads to its hydrolytic cleavage. On the bottom, Umberto Tonellato (1935-2020), in formal university gown and hat, one of the founders of Supramolecular Chemistry in Italy and of the Supramolecular and Systems Chemistry group in Padova. More information can be found in the Minireview by P. Scrimin et al.

[Cover Picture]

Dr. Luca Gabrielli, Prof. Dr. Leonard J. Prins, Prof. Dr. Federico Rastrelli, Prof. Dr. Fabrizio Mancin, Prof. Dr. Paolo Scrimin

doi.org/10.1002/ejoc.202001095

Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides

A robust constitution: α- and β-hydroxy phosphine oxides are synthesized by a fast and chemoselective one-pot addition of the in-situ generated highly polarized lithium phosphides (LiPR2) to both aldehydes and epoxides using eutectic mixtures as biorenewable reaction media. Despite the well-known air and moisture sensitivity of organolithium compounds, the proposed synthetic protocol enables all reactions (preparation and reactivity of LiPR2) to be performed at room temperature, in protic solvents, and under air atmosphere.

[Full Papers]

Dr. Luciana Cicco, Alba Fombona-Pascual, Alba Sánchez-Condado, Prof. Gabino A. Carriedo, Dr. Filippo M. Perna, Prof. Vito Capriati, Prof. Alejandro Presa Soto, Prof. Joaquín García-Álvarez

doi.org/10.1002/cssc.202001449

Ligand-Free Suzuki-Miyaura Cross-Coupling Reactions in Deep Eutectic Solvents: Synthesis of Benzodithiophene Derivatives and Study of their Optical and Electrochemical Performance

Valuable π-conjugated benzodithiophene derivatives have been prepared through a ligand-free Suzuki-Miyaura cross-coupling reaction, under mild aerobic conditions, in deep eutectic solvents (DESs) as environmentally responsible reaction media, and their optical and electrochemical properties were investigated.

[Full Papers]

Valentina Pelliccioli, Dr. Giuseppe Dilauro, Sara Grecchi, Dr. Serena Arnaboldi, Prof. Claudia Graiff, Dr. Filippo M. Perna, Dr. Paola Vitale, Prof. Emanuela Licandro, Dr. Alessandro Aliprandi, Dr. Silvia Cauteruccio, Prof. Vito Capriati

doi.org/10.1002/ejoc.202000889

Towards Solar Factories: Prospects of Solar-to-Chemical Energy Conversion using Colloidal Semiconductor Photosynthetic Systems

A stellar protocol: Solar-to-Chemical energy conversion allows the synthesis of a manifold of redox products via decoupled endergonic processes. Focusing on colloidal semiconductor materials, this Viewpoint aims to establish an interdisciplinary experimental protocol, stimulating collaborative research in photon-to-molecule energy conversion.

[Viewpoints]

Dr. Amedeo Agosti, Prof. Mirco Natali, Prof. Lilac Amirav, Prof. Giacomo Bergamini

doi.org/10.1002/cssc.202001274

Sol-Gel Nanocoatings to Functionalize Fibers and Textiles: A Critical Perspective

Sol-gel functionalized nanotextiles? Get a practical perspective! Environmentally friendly and easily applied silica-based sol-gel nanocoatings are used by selected textile companies to produce high performance textile fabrics endowed with new functional properties. This study identifies the main technical and economic reasons that will drive widespread application of hybrid sol-gel coatings in the textile industry.

[Reviews]

Dr. Rosaria Ciriminna, Dr. Yael Albo, Dr. Mario Pagliaro

doi.org/10.1002/slct.202001897

Aza- and Mixed Thia/Aza-Macrocyclic Receptors with Quinoline-Bearing Pendant Arms for Optical Discrimination of Zinc(II) or Cadmium(II) Ions

A strong arm: The sensing and recognition properties of two fluorescent chemosensors featuring [9]aneN3 (L1) and [12]aneNS3 (L2) as receptor units and a quinoline pendant arm with an amide group as functional group spacer have been studied. The combination of these units resulted in a selective optical response of L1 and L2 through a CHEF effect towards Zn2+ and Cd2+, following the formation of a 1 : 1 and a 1 : 2 metal-to-ligand complex, respectively.

[Full Papers]

Dr. Alessandra Garau, Prof. M. Carla Aragoni, Prof. Massimiliano Arca, Prof. Andrea Bencini, Prof. Alexander J. Blake, Prof. Claudia Caltagirone, Prof. Claudia Giorgi, Prof. Vito Lippolis, Dr. Mariano Andrea Scorciapino

doi.org/10.1002/cplu.202000444

Porphycene Protonation: A Fast and Reversible Reaction Enabling Optical Transduction for Acid Sensing

Going green: An effective and reversible color change (from blue to green) of a porphycene film when exposed to acid vapours is demonstrated. The applicability of porphycene thin films in acidochromic vapor sensing is demonstrated by using surface differential reflectivity technique.

[Articles]

Dr. Alberto Bossi, Prof. Jacek Waluk, Dr. Rossella Yivlialin, Dr. Marta Penconi, Prof. Marcello Campione, Prof. Gianlorenzo Bussetti

doi.org/10.1002/cptc.202000142

Transition-Metal-Mediated versus Tetrazine-Triggered Bioorthogonal Release Reactions: Direct Comparison and Combinations Thereof

Direct comparison: Two different metal-promoted as well as the tetrazine-triggered bioorthogonal cleavage reactions were investigated with the goal to directly compare the release yield, reaction rates and efficiency of the transformations under identical experimental conditions. In addition, this study shows that some of these reactions are mutually orthogonal, which opens up the possibility to perform simultaneous multiple decaging experiments.

[Communications]

Francesca Mancuso, Michal Rahm, Dr. Rastislav Dzijak, Dr. Helena Mertlíková-Kaiserová, Dr. Milan Vrabel

doi.org/10.1002/cplu.202000477

From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies

Natural products are a privileged class of compounds with high diversity which are suitable for inspiring new rationally designed multi-target drugs. Herein, a multi-disciplinary approach that covers the structural and pharmacological characterization of NPs for developing semisynthetic and synthetic derivatives with optimized potency/selectivity towards specific targets in the inflammatory/cancer field is proposed.

[Minireview]

Dr. Simona De Vita, Prof. Stefania Terracciano, Prof. Ines Bruno, Prof. Maria Giovanna Chini

doi.org/10.1002/ejoc.202000469

Nanoparticle-Catalysed 1,3-Dipolar Cycloadditions

This minireview summarises the field of inorganic nanocatalysts applied to 1,3-dipolar cycloadditions and emphases the various metals involved, their structure, characterisation, recyclability, and their preparation. Emphasis has also been given to improvements with respect to cycloadditions performed with the usual (non-nano) catalysts. For the sake of clarity, the results were summarised according to the 1,3-dipole type, namely, azomethine ylides, azomethine imines, nitrone, nitrilimine, and azides.

[Minireview]

Dr. Alessandro Ponti, Dr. Giorgio Molteni

doi.org/10.1002/ejoc.202000738

Elucidating the Relationship between Multiradical Character and Predicted Singlet Fission Activity

An inherent biradicaloid character evaluated through CASSCF is shown to correlate with computed energy levels suitable for singlet fission, by testing a large and statistically significant set of molecules.

[Articles]

Ömer H. Omar, Dr. Daniele Padula, Prof. Alessandro Troisi

doi.org/10.1002/cptc.202000098

A Novel Li+-Conducting Polymer Membrane Gelled by Fluorine-Free Electrolyte Solutions for Li-Ion Batteries

Saved by the gel: In situ gel polymer electrolyte (GPE) preparation, directly in the T-shape cell used performance tests, is proposed. The GPE has novel composition, with a fluorine-free LiBOB salts. The SnC|LiFePO4 lithium-ion battery, having in situ GPE, exhibits a high capacity of about 150 mAh g−1 through a course of cycling.

[Articles]

Dr. Maria Assunta Navarra, Dr. Akiko Tsurumaki, Dr. Francesco Maria Vitucci, Dr. Annalisa Paolone, Dr. Oriele Palumbo, Prof. Stefania Panero

doi.org/10.1002/batt.202000078

Optical Properties of Various Strontium Bismuthates: Luminescence and UV-induced Photocoloration

Mechanistic scheme of the low-temperature photoluminescence and UV-induced formation of color centers of the three bismuthates examined

[Articles]

Prof. Dmitry S. Shtarev, Dr. Anna V. Shtareva, Dr. Nikita I. Selivanov, Prof. Vladimir K. Ryabchuk, Dr. Aida V. Rudakova, Prof. Nick Serpone

doi.org/10.1002/cptc.202000128

Exploring the Chemoselectivity towards Cysteine Arylation by Cyclometallated AuIII Compounds: New Mechanistic Insights

Getting your gold right: Cyclometallated AuIII complexes with bidentate C^N-donor ligands enable chemoselective cysteine modification of peptides by C−S bond-forming reductive elimination. By using combined high-resolution mass spectrometry and QM/MM studies, further understanding of the mechanisms of AuIII-templated cross-coupling leading to cysteine arylation was achieved; this is essential to design selective gold compounds for bio-orthogonal reactions.

[Communications]

Sophie R. Thomas, Dr. Riccardo Bonsignore, Jorge Sánchez Escudero, Dr. Samuel M. Meier-Menches, Dr. Christopher M. Brown, Prof. Michael O. Wolf, Prof. Giampaolo Barone, Dr. Louis Y. P. Luk, Prof. Angela Casini

doi.org/10.1002/cbic.202000262

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

See three with glee: Tethering three rather than a single peptidic αvβ6 integrin ligand to a radionuclide lets tumor tissue light up brightly in tomographic images, potentially enabling a more sensitive diagnosis of various cancers.

[Full Papers]

Neil Gerard Quigley, Dr. Stefano Tomassi, Dr. Francesco Saverio Di Leva, Dr. Salvatore Di Maro, Dr. Frauke Richter, Dr. Katja Steiger, Prof. Dr. Susanne Kossatz, Prof. Dr. Luciana Marinelli, Dr. Johannes Notni

doi.org/10.1002/cbic.202000200

Enhancement of Functional Properties of Liquid Electrolytes for Lithium-Ion Batteries by Addition of Pyrrolidinium-Based Ionic Liquids with Long Alkyl-Chains

The pursuit of electrolytes: Innovative non-aqueous electrolytes for Li-ion batteries with superior safety features compared to commercial products are formulated and characterized: here, the unique physico-chemical properties of ionic liquids to push the capability of liquid electrolytes beyond the state-of-the-art are exploited.

[Articles]

Arcangelo Celeste, Dr. Laura Silvestri, Dr. Marco Agostini, Matthew Sadd, Stefano Palumbo, Dr. Jaya Kumar Panda, Dr. Aleksandar Matic, Dr. Vittorio Pellegrini, Dr. Sergio Brutti

doi.org/10.1002/batt.202000070

[1]Benzothieno[3,2-b][1]benzothiophene-Phthalocyanine Derivatives: A Subclass of Solution-Processable Electron-Rich Hole Transport Materials

Ready to use: The phthalocyanine ring was functionalized with benzothienobenzothiophene moieties to synthesize two solution-processable p-type macrocyclic semiconductors and to investigate their chemical, optical and electrochemical properties from an experimental and theoretical point of view. Their implementation as hole transporters in mixed-ion perovskite solar cells successfully gave power conversion efficiencies up to 14.13 % even in undoped devices.

[Full Papers]

Dr. Gloria Zanotti, Dr. Nicola Angelini, Dr. Giuseppe Mattioli, Dr. Anna Maria Paoletti, Dr. Giovanna Pennesi, Dr. Daniela Caschera, Dr. Anatoly Petrovich Sobolev, Prof. Luca Beverina, Adiel Mauro Calascibetta, Dr. Alessandro Sanzone, Prof. Aldo Di Carlo, Dr. Beatrice Berionni Berna, Dr. Sara Pescetelli, Dr. Antonio Agresti

doi.org/10.1002/cplu.202000281

Additive Manufacturing of Aqueous-Processed LiMn2O4 Thick Electrodes for High-Energy-Density Lithium-Ion Batteries

Robocasting additive manufacturing (AM) via aqueous processing for thick electrodes production is presented. Such 3D printing technology is: i) environmentally friendly, since it works well with water and green binders; ii) fast, due to very short deposition times and rapid drying process; iii) easily scalable. The electrodes are produced by extruding pastes with very high solid loadings. Our results on LiM2O4 cathode may boost the development of greener, lower cost and more efficient new generation of LIBs for household energy storage or micro-battery technology.

[Articles]

Lorenzo Airoldi, Umberto Anselmi-Tamburini, Barbara Vigani, Silvia Rossi, Piercarlo Mustarelli, Dr. Eliana Quartarone

doi.org/10.1002/batt.202000058