In Situ Electrochemical Investigations of Inherently Chiral 2,2′-Biindole Architectures with Oligothiophene Terminals

AbstractThe synthesis and characterization of three new inherently chiral N,N′‐dipropyl‐3,3′‐diheteroaryl‐2,2′‐biindole monomers, nicknamed Ind2T4, Ind2T6 and Ind2Ph2T4, which differ in the number of thiophenes as terminals, are reported. In addition to a full monomer characterization, stable electroactive oligomeric films were obtained by electro‐oxidation upon cycling to potentials which activate the thiophene terminals. Cyclic voltammetry, UV‐Vis‐NIR spectroelectrochemistry and in situ conductance measurements show that oligomeric films of Ind2T6 present the best stability and electrochromic switching performance. Enantioselective tests with a chiral ferrocene amine clearly show the potential as chiral selectors for analytical and sensing purposes

Conductance and spectroscopic mapping of EDOT polymer films upon electrochemical doping

Abstract This paper deals with the electrochemical doping of different poly(ethylenedioxythiophene) (PEDOT)-based active layers performed in an organic electrochemical transistor configuration through the mapping of in situ conductance trends during electrochemical doping and dedoping. The experiments are complemented by UV/Vis/NIR in situ spectroelectrochemistry in the wavelength range from 400 to 1600 nm, which allow monitoring of the development of the neutral and charged redox species. Both electropolymerized EDOT-based layers and solution-processed chemically synthesized PEDOT films are characterized. In addition to pure electropolymerized PEDOT (e-PEDOT), tris(4-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)phenyl) (TPA-EDOT3) is electrodeposited to generate highly branched networks of P(TPA-EDOT3). The solution-deposited PEDOT films contain poly(ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with ratios of 1:2.5 and 1:6. Overall, we find that e-PEDOT and PEDOT:PSS(1:2.5) behave like classical conjugated polymers with a plateau-like conductance over a wide potential region. In contrast, PEDOT:PSS(1:6) and P(TPA-EDOT3) show rather bell-shaped conductance profiles. The mixed-valence conductivity model is used to interpret the experimental results in terms of the number of accessible redox states. We suggest that the bell-shaped conductance in the case of PEDOT:PSS(1:6) is caused by a high amount of PSS insulator that limits the inter-chain interaction between PEDOT moieties and in the case of P(TPA-EDOT3) by its distorted molecular architecture

TOWARDS THE DEVELOPMENT OF BENCH TESTING FOR LOWER-LIMB PROSTHETIC SOCKETS FOR SPORT APPLICATIONS

Prosthetic sockets are the bespoken part of lower-limb prostheses. Knowledge about the mechanical properties of sockets is essential to ensure patient safety and comply with current medical device regulations. This includes sockets designed for sport activities. Unfortunately, the literature is extremely limited and contradictory as described in a recent systematic review. The aim of this study was to initiate a research activity aiming to design a mechanical bench system for socket testing and perform a comparative analysis of the ultimate strength of alternative socket layups. Results highlight substantial differences in the maximum loading at failure, stressing the importance of increasing the knowledge about socket mechanical properties to support prosthetists provide reliable and safe products to patients and athletes

Young para-athletes display more hedonic well-being than people with disabilities not taking part in competitive sports: insights from a multi-country survey

Hedonic well-being relates to how individuals experience and rate their lives. People with disabilities due to their pathology may more frequently suffer from anxiety and depressive disorders than their able-bodied counterparts. Sports participation is an essential way to cope with disability. On the other hand, compared with their able-bodied peers, para-athletes undergo a unique series of stressors. Little is known in terms of hedonic well-being in this specific population. We present the results of a multi-country survey of self-perceived hedonic well-being by para-athletes of different sports disciplines and a control group (disabled individuals not playing competitive sports), using the “Psychological General Well-Being Index” (PGWBI). We included 1,208 participants, aged 17.39 years, 58.4% male, 41.6% female, and 70.3% para-athletes. Para-athletes exhibited higher well-being than disabled people, for all domains of the PGWBI scale. The nature of disability/impairment was significant, with those with acquired disability reporting lower well-being. Those taking part in wheelchair basketball, para-athletics, and para-swimming competitions had a higher likelihood of reporting well-being, whereas those engaged in wheelchair rugby exhibited lower well-being compared with controls. This large-scale investigation can enable a better understanding of the self-perceived hedonic well-being of disabled people

Indoles and Biindoles: Synthesis of Powerful Tools for Pharmaceutical and Materials Sciences

Part 1: synthesis of indoles as potential bioactive compounds Indole and related derivatives play a strong relevant role in heterocyclic chemistry. They are diffused in a huge array of different natural products[1], many of them with intriguing biological activity.[2] Other applications spread uncountable fields: material science, fragrances, agrochemicals, pigments and dyes and many more.[3] It\u2019s not surprising then that many efforts are made by organic chemists to find not only synthetic methods to achieve indole fragments but also new functionalization protocols to afford with ease complex targets. Recently, Penoni group afforded a novel regioselective indole synthesis via annulation of variously substituted nitrosoarenes and alkynes[4,5] (Figure 1). Main feature of this reaction is possibility to directly prepare N-hydroxyindoles derivatives, when 4-nitronitrosobenzene is employed as reaction partner. High efficiency on nitrosoarene-alkyne cycloaddition was noticed by trapping the formed unstable N-OH indole product by methylation or interception with other electrophiles. Concerning other alkyne reactions with other substituted nitrosobenzenes, indoles were detected as products; this feature was exploited to prepare marine alkaloids meridianins and some modified aminoacids[6] (Figure 1). Reaction is supposed to pass through a radical mechanism[7] . Figure 1: annulation reaction between alkynes and nitrosoarenes 3-Acylindoles(e.g. pravadoline, SCB01A, BPR0L075) are known to be bioactive compounds and recent studies highlighted their interesting properties[8] and various synthetic approaches[9]. However, not many indolization protocols are known to afford directly 3-acylindoles starting from easily available reactants. Research topic was therefore focused on applying and optimizing nitrosoarene-alkyne one pot annulation 2 approach for the preparation of highly functionalizable compounds and/or biologically active products having the 3-aroylindole fragment (Figure 2). Noticeably, after careful reaction optimization, unprotected Nhydroxy-3-aroylindoles were regioselectively detected as main products in most cases and recovered as perfectly stable solid after precipitation with no need of protecting groups[10\u201312] . Internal alkynes gave poor reactivity. Figure 2: annulation reaction between alkynones and nitrosoarenes. Interestingly, reaction between 4-nitronitrosobenzene and 3-bromo-1-phenylprop-2-yn-1-one gave regioselectively a 2-brominated indole compound. It is set as an objective for the near future a wide substrate scope for synthesis of different 2-brominated indoles (Figure 3). Studies of reactivity of the latter compounds towards classical cross coupling reactions is expected as well (Figure 3). Figure 3: synthesis of a N-hydroxy-3-aroyl-2-bromo-indole (left); reactivity of the latter to classic cross coupling reactions (right). Part 2: synthesis of new organic semiconductors based on 2,2\u2019- and 3,3\u2019- biindole backbone 3 Inherently chiral materials based on 2,2\u2019-biindole are characterized by an atropoisomeric backbone of two 2,2\u2019 interconnected indole rings bearing 3,3\u2019 substituents usually constituted by 2,2\u2019-bitiophene units(Ind2T4, Figure 4). Those substituents play the double role of hindering rotation around the interannular bond and endowing system with specific properties. Main application of inherently chiral 2,2\u2019-biindoles is as starting materials to obtain enantiopure oligomeric selectors in chiral electrochemistry[13] . Monomer oligomerization is usually performed in electrochemical cell by many repeating anodic voltametric cycles to afford an oligomeric coating directly on working electrode. Our interest in the chemistry of indoles led us to explore the opportunity to get some analogous structure by structural modification of 3,3\u2019-substituents. Introduction of a \u3c0 spacer (Ind2Ph2T4, Ind2T6, Figure 4) was performed to study its influence on chiral properties of resulting oligomers, whilst introduction of a benzochalchogenodiazole subunit allows to achieve a donor-acceptor moiety with interesting optical properties (Ind2BTD2T4, Ind2BSeD2T4, Figure 4). Figure 4: enantiomers of Ind2T4 (left); target 2,2\u2019-biindoles (right). R = alkyl. Key core for synthesis of these compounds is a Larock-type 5-endo-dig double indole ring closure starting from compound 1 (Scheme 1), as published by Abbiati in 2006[14]. This protocol shows good versatility as by variation of aryl- or heteroaryl halide reaction partner is possible to prepare different 3,3\u2019-diaryl/heteroaryl 2,2\u2019-biindoles although in good to mediocre yield. Only racemate compounds are afforded due to lack of any chiral catalyst. Subsequent nitrogen alkylation step is fundamental to ensure good solubility for processing. Scheme 1: synthesis of 2,2\u2019-biindoles starting from 1 and an aryl/heteroaryl halide. 4 All new compounds have been deeply characterized either monomeric or oligomeric. Separation of Ind2Ph2T4, Ind2T6 in their two enantiomers was performed through semipreparative chiral HPLC, as up to now synthetic method allows only to afford targets as racemate mixtures. After electrodeposition, Ind2Ph2T4 and Ind2T6 enantiopure oligomeric films showed great enantioselectivity towards both enantiomers of a chiral ferrocenylamine (Figure 5). Figure 5: cyclic voltammetry graphs showing different oxidation peaks for enantiopure oligo N-Pr-Ind2Ph2T4 (left) and N-Pr-Ind2T6 (right) towards two enantiomers of a chiral ferrocenylamine (bottom). Concerning Ind2BTD2T4 and Ind2BSeD2T4, full characterization of monomers and electroactive films has been carried out. Enantiorecognition tests are planned for next future. Since Larock-type ring closure reaction has been proved very useful although mediocre yielding, a new and more performant synthetic plan to afford Ind2T4 has been optimized (Scheme 2). Key step is high yield SuzukiMiyaura cross coupling reaction starting from compound 5. Future developments concern on use of different boronic pinacol esters to afford Ind2Ph2T4, Ind2T6, Ind2BTD2T4 and Ind2BSeD2T4 in better yields as well. 5 Scheme 2: synthesis of Ind2T4 passing through a Suzuki cross coupling step. Structural analogue 2,2\u2019-diheteroaryl-3,3\u2019-biindole 3,3\u2019-Ind2T4 (Figure 6) was synthetized as well with the aim to investigate its ability as chiral selectors. Unfortunately, when trying to separate them with chiral HPLC, enantiomers peaks coalescence was noticed even at room temperature, suggesting configurational instability. Figure 6: synthesis of 3,3\u2019-Ind2T4 (up); chiral HPLC profiles at different temperatures (bottom). Computational studies indicated possibility to achieve configurational stability for 3,3\u2019-biindoles by nitrogen alkylation with very bulky tertbutyl group. Experiments in this direction are currently ongoing. References: [1] R. J. Sundberg, The Chemistry of Indoles, New York, 1970. [2] V. Sharma, P. Kumar, D. Pathak, J. Heterocycl. Chem. 2010, 47, 491\u2013502. [3] T. C. Barden, Peptides 2011, 26, 31\u201346. [4] A. Penoni, K. M. Nicholas, Chem. Commun. 2002, 2, 484\u2013485. [5] A. Penoni, J. Volkmann, K. M. Nicholas, Org. Lett. 2002, 4, 699\u2013701. [6] F. Tibiletti, M. Simonetti, K. M. Nicholas, G. Palmisano, M. Parravicini, F. Imbesi, S. Tollari, A. Penoni, 6 Tetrahedron 2010, 66, 1280\u20131288. [7] A. Penoni, G. Palmisano, Y. Zhao, K. N. Houk, J. Volkman, K. M. Nicholas, J. Am. Chem. Soc. 2009, 131, 653\u2013661. [8] D. G. Zhao, J. Chen, Y. R. Du, Y. Y. Ma, Y. X. Chen, K. Gao, B. R. Hu, J. Med. Chem. 2013, 56, 1467\u2013 1477. [9] S. J. Yao, Z. H. Ren, Z. H. Guan, Tetrahedron Lett. 2016, 57, 3892\u20133901. [10] G. Ieronimo, G. Palmisano, A. Maspero, A. Marzorati, L. Scapinello, N. Masciocchi, G. Cravotto, A. Barge, M. Simonetti, K. L. Ameta, et al., Org. Biomol. Chem. 2018, 16, 6853\u20136859. [11] L. Scapinello, A. Maspero, S. Tollari, G. Palmisano, K. M. Nicholas, A. Penoni, J. Vis. Exp. 2020, 155, 1\u2013 12. [12] L. Scapinello, F. Vavassori, G. Ieronimo, K. L. Ameta, G. Cravotto, M. Simonetti, S. Tollari, G. Palmisano, A. Maspero, K. M. Nicholas, et al., Manuscript in Preparation, 2020. [13] S. Arnaboldi, T. Benincori, A. Penoni, L. Vaghi, R. Cirilli, S. Abbate, G. Longhi, G. Mazzeo, S. Grecchi, M. Panigati, et al., Chem. Sci. 2019, 10, 2708\u20132717. [14] G. Abbiati, A. Arcadi, E. Beccalli, G. Bianchi, F. Marinelli, E. Rossi, Tetrahedron 2006, 62, 3033\u2013303

Cover Feature: In Situ Electrochemical Investigations of Inherently Chiral 2,2′-Biindole Architectures with Oligothiophene Terminals (ChemElectroChem 17/2021)

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Synthesis, Characterization and DNA-Binding Affinity of a New Zinc(II) Bis(5-methoxy-indol-3-yl)propane-1,3-dione Complex

The novel zinc(II) µ-oxo-bridged-dimeric complex [Zn2(µ-O)2(BMIP)2] (BMIP = 1,3-bis(5-methoxy-1-methyl-1H-indol-3-yl)propane-1,3-dione), 1, was synthetized and fully characterized. The spectral data indicate a zincoxane molecular structure, with the BMIP ligand coordinating in its neutral form via its oxygen atoms. Structural changes in 1 in dimethylsulfoxide (DMSO) were evidenced by means of spectroscopic techniques including infrared absorption and nuclear magnetic resonance, showing DMSO entrance in the coordination sphere of the metal ion. The resulting complex [Zn2(µ-O)2(BMIP)2(DMSO)], 2, readily reacts in the presence of N-methyl-imidazole (NMI), a liquid-phase nucleoside mimic, to form [Zn2(µ-O)2(BMIP)2(NMI)], 3, through DMSO displacement. The three complexes show high thermal stability, demonstrating that 1 has high affinity for hard nucleophiles. Finally, with the aim of probing the suitability of this system as model scaffold for new potential anticancer metallodrugs, the interactions of 1 with calf thymus DNA were investigated in vitro in pseudo-physiological environment through UV-Vis absorption and fluorescence emission spectroscopy, as well as time-resolved fluorescence studies. The latter analyses revealed that [Zn2(µ-O)2(BMIP)2(DMSO)] binds to DNA with high affinity upon DMSO displacement, opening new perspectives for the development of optimized drug substances

Asymmetric Phenyl Substitution: An Effective Strategy to Enhance the Photosensitizing Potential of Curcuminoids

Curcumin has been demonstrated to exhibit photosensitized bactericidal activity. However, the full exploitation of curcumin as a photo-pharmaceutical active principle is hindered by fast deactivation of the excited state through the transfer of the enol proton to the keto oxygen. Introducing an asymmetry in the molecular structure through acting on the phenyl substituents is expected to be a valuable strategy to impair this undesired de-excitation mechanism competing with the therapeutically relevant ones. In this study, two asymmetric curcumin analogs were synthesized and characterized as to their electronic-state transition spectroscopic properties. Fluorescence decay distributions were also reconstructed. Their analysis confirmed the substantial stabilization of the fluorescent state with respect to the parent compound. Nuclear magnetic resonance experiments were performed with the aim of determining the structural features of the keto–enol ring and the strength of the keto–enol hydrogen bond. Electronic structure calculations were also undertaken to elucidate the effects of substitution on the features of the keto–enol semi-aromatic system and the proneness to proton transfer. Finally, their singlet oxygen-generation efficiency was compared to that of curcumin through the 9,10-dimethylanthracene fluorescent assay