Aromatic Interactions Research Articles

Colla corii asini–derived peptides as tyrosinase inhibitors: identification, inhibitory activity and molecular mechanism

SummaryThe aim of the present study was to investigate the effect of peptides derived from Colla corii asini on tyrosinase. The sequences of Colla corii asini–derived peptides were identified using mass spectrometry. To characterise the potential peptides with tyrosinase inhibitory activity and clarify their molecular mechanism, both in silico digestion and molecular docking were used. In addition, the tyrosinase inhibitory activities of potential peptides in vitro were also validated. The results showed that Colla corii asini consisted of 472 peptides, and most peptides derived from collagen. Peptides DGGR, DGD, NAGE, LVGE and GSEG were released from the digestion of Colla corii asini‐derived peptides and possessed potent inhibitory activity against tyrosinase with IC50 values of 0.92, 0.50, 0.77, 0.66 and 0.69 mg mL−1, respectively. The molecular interaction results showed that hydrogen bond and van der Waals interactions are important forces in the interaction of peptides with tyrosinase. Surface forces containing aromatic interaction, hydrogen bond, hydrophilicity and solvent‐accessible surface contributed to the interaction between tyrosinase and peptides.

Aqueous-Based Polyimine Functionalization of Cellulose Nanofibrils for Effective Drying and Polymer Composite Reinforcement

A simple strategy was developed to synthesize polyimine-coated cellulose nanofibrils (CNF) for effective CNF drying and composite reinforcement. The polyimine was synthesized in an aqueous medium using a selective hydrophilic and hydrophobic component that forces the polyimine to precipitate, which prevents the reverse imine reaction. The polyimine coating allowed the CNF to be easily oven-dried while maintaining a fibrillar morphology to provide mechanical reinforcement in poly(ethylene terephthalate glycol) (PETG) composites. In comparison, poor mechanical performance and a heterogeneous fracture surface were observed when the coated CNF were incorporated into poly(l-lactide) (PLA) composites. It is hypothesized that intermolecular aromatic–aromatic interactions are formed at the interface between fibers and the polymer matrix in the PETG system, while no such phenomena occur in the PLA system. Overall, this facile strategy to produce modified, easily dried CNF can be adapted to produce polyimine-coated CNF with unique functionalities that are useful in a range of applications.

Spontaneous Transfer of Indocyanine Green from Liposomes to Albumin Is Inhibited by the Antioxidant α-Tocopherol.

Indocyanine Green (ICG) is a clinically approved organic dye with near-infrared absorption and fluorescence. Over the years, many efforts to improve the photophysical and pharmacokinetic properties of ICG have investigated numerous nanoparticle formulations, especially liposomes with membrane-embedded ICG. A series of systematic absorption and fluorescence experiments, including FRET experiments using ICG as a fluorescence energy acceptor, found that ICG transfers spontaneously from liposomes to albumin protein residing in the external solution with a half-life of ∼10 min at 37 °C. Moreover, transfer of ICG from liposome membranes to external albumin reduces light-activated leakage from thermosensitive liposomes with membrane-embedded ICG. A survey of lipophilic liposome additives discovered that the presence of clinically approved antioxidant, α-tocopherol, greatly increases ICG retention in the liposomes (presumably by forming favorable aromatic stacking interactions), inhibits ICG photobleaching and prevents albumin-induced reduction of light-triggered liposome leakage. This new insight will help researchers with the specific task of optimizing ICG-containing liposomes for fluorescence imaging or phototherapeutics. More broadly, the results suggest a broader design concept concerning light triggered liposome leakage, that is, proximity of the light absorbing dye to the bilayer membrane is a critical design feature that impacts the extent of liposome leakage.

A Statistical Analysis of the Sequence and Structure of Thermophilic and Non-Thermophilic Proteins.

Thermophilic proteins have various practical applications in theoretical research and in industry. In recent years, the demand for thermophilic proteins on an industrial scale has been increasing; therefore, the engineering of thermophilic proteins has become a hot direction in the field of protein engineering. However, the exact mechanism of thermostability of proteins is not yet known, for engineering thermophilic proteins knowing the basis of thermostability is necessary. In order to understand the basis of the thermostability in proteins, we have made a statistical analysis of the sequences, secondary structures, hydrogen bonds, salt bridges, DHA (Donor–Hydrogen–Accepter) angles, and bond lengths of ten pairs of thermophilic proteins and their non-thermophilic orthologous. Our findings suggest that polar amino acids contribute to thermostability in proteins by forming hydrogen bonds and salt bridges which provide resistance against protein denaturation. Short bond length and a wider DHA angle provide greater bond stability in thermophilic proteins. Moreover, the increased frequency of aromatic amino acids in thermophilic proteins contributes to thermal stability by forming more aromatic interactions. Additionally, the coil, helix, and loop in the secondary structure also contribute to thermostability.

Characterisation of a Seneca Valley virus thermostable mutant

Seneca Valley virus (SVV) is a newly discovered picornavirus in the Senecavirus genus. SVV-001 strain has shown promise as an oncolytic virus against tumors with neuroendocrine features. There is a need to use a structure-based approach to develop virus-like particles capable to mimicking the architecture of naturally occurring empty capsids that can be used as vaccines or as carriers for targeted cancer treatment. However, these empty capsids are inherently less stable, and tedious to purify. This warrants investigation into factors which confer the SVV capsid stability and into combining this knowledge to recombinantly express stable SVV VLPs. In this study, we isolated a thermostable mutant of SVV by thermal selection assays and we characterized a single mutation located in a capsid protein. The cryo-EM map of this mutant showed conformational shifts that facilitated the formation of additional hydrogen bonds and aromatic interactions, which could serve as capsid stabilizing factors.

Antibody CDR amino acids underlying the functionality of antibody repertoires in recognizing diverse protein antigens

Antibodies recognize protein antigens with exquisite specificity in a complex aqueous environment, where interfacial waters are an integral part of the antibody–protein complex interfaces. In this work, we elucidate, with computational analyses, the principles governing the antibodies’ specificity and affinity towards their cognate protein antigens in the presence of explicit interfacial waters. Experimentally, in four model antibody–protein complexes, we compared the contributions of the interaction types in antibody–protein antigen complex interfaces with the antibody variants selected from phage-displayed synthetic antibody libraries. Evidently, the specific interactions involving a subset of aromatic CDR (complementarity determining region) residues largely form the predominant determinant underlying the specificity of the antibody–protein complexes in nature. The interfacial direct/water-mediated hydrogen bonds accompanying the CDR aromatic interactions are optimized locally but contribute little in determining the epitope location. The results provide insights into the phenomenon that natural antibodies with limited sequence and structural variations in an antibody repertoire can recognize seemingly unlimited protein antigens. Our work suggests guidelines in designing functional artificial antibody repertoires with practical applications in developing novel antibody-based therapeutics and diagnostics for treating and preventing human diseases.

Omicron Binding Mode: Contact Analysis and Dynamics of the Omicron Receptor-Binding Domain in Complex with ACE2.

On 26 November 2021, the WHO classified the Omicron variant of the SARS-CoV-2 virus (B.1.1.529 lineage) as a variant of concern (VOC) (COVID-19 Variant Data, Department of Health, 2022). The Omicron variant contains as many as 26 unique mutations of effects not yet determined (Venkatakrishnan, A., Open Science Framework, 2021). Out of its total of 34 Spike protein mutations, 15 are located on the receptor-binding domain (S-RBD) (Stanford Coronavirus Antiviral & Resistance Database, 2022) that directly contacts the angiotensin-converting enzyme 2 (ACE2) host receptor and is also a primary target for antibodies. Here, we studied the binding mode of the S-RBD domain of the Spike protein carrying the Omicron mutations and the globular domain of human ACE2 using molecular dynamics (MD) simulations. We identified new and key Omicron-specific interactions such as R493 (of mutation Q493R), which forms salt bridges both with E35 and D38 of ACE2, Y501 (N501Y), which forms an edge-to-face aromatic interaction with Y41, and Y505 (Y505H), which makes an H-bond with E37 and K353. The glycan chains of ACE2 also bind differently in the WT and Omicron variants in response to different charge distributions on the surface of Spike proteins. However, while the Omicron mutations considerably improve the overall electrostatic fit of the two interfaces, the total number of specific and favorable interactions between the two does not increase. The dynamics of the complexes are highly affected too, making the Omicron S-RBD:ACE2 complex more rigid; the two main interaction sites, Patches I and II, isolated in the WT complex, become connected in the Omicron complex through the alternating interaction of R493 and R498 with E35 and D38.

Molecular Mechanism of Organic Crystal Nucleation: A Perspective of Solution Chemistry and Polymorphism

Crystal nucleation determining the formation and assembly pathway of first organic materials is the central science of various scientific disciplines such as chemical, geochemical, biological, and synthetic materials. However, our current understanding of the molecular mechanisms of nucleation remains limited. Over the past decades, the advancements of new experimental and computational techniques have renewed numerous interests in detailed molecular mechanisms of crystal nucleation, especially structure evolution and solution chemistry. These efforts bifurcate into two categories: (modified) classical nucleation theory (CNT) and non-classical nucleation mechanisms. In this review, we briefly introduce the two nucleation mechanisms and summarize current molecular understandings of crystal nucleation that are specifically applied in polymorphic crystallization systems of small organic molecules. Many important aspects of crystal nucleation including molecular association, solvation, aromatic interactions, and hierarchy in intermolecular interactions were examined and discussed for a series of organic molecular systems. The new understandings relating to molecular self-assembly in nucleating systems have suggested more complex multiple nucleation pathways that are associated with the formation and evolution of molecular aggregates in solution.

Mononuclear Tricoordinate Copper(I) and Silver(I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin.

Reaction of two equivalents of the bulky 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with MX (being M = Cu+, Ag+; and X = Cl−, Br−, I−) in acetonitrile afforded neutral complexes of the type [MXL2] [CuClL2].2CH3CN (1a); [CuBrL2].2CH3CN (1b); [CuIL2] (1c): [AgClL2] (2a); [AgBrL2] (2b) and [AgIL2] (2c). The two aromatic groups in free ligand were found to be trans with respect to the thiourea unit, which was a reason to link the ligand molecules via intermolecular hydrogen bonding. Intramolecular hydrogen bonding was observed in all metal complexes. The copper complexes 1a and 1b are acetonitrile solvated and show not only intra- but also intermolecular hydrogen bonding between the coordinated thiourea and the solvated acetonitrile molecules. Silver complexes reported here are the first examples of structurally characterized tricoordinated thiourea-stabilized monomeric silver(I) halides. Molecular docking studies were carried out to analyze the binding modes of the metal complexes inside the active site of the human insulin (HI) protein. Analysis of the docked conformations revealed that the electrostatic and aromatic interactions of the protein N-terminal residues (i.e., Phe and His) may assist in anchoring and stabilizing the metal complexes inside the active site. According to the results of docking studies, the silver complexes exhibited the strongest inhibitory capability against the HI protein, which possesses a deactivating group, directly bonded to silver. All compounds were fully characterized by elemental analysis, NMR spectroscopy, and molecular structures of the ligand, and five out of six metal complexes were also confirmed by single-crystal X-ray diffraction.

The Pink Box: Exclusive Homochiral Aromatic Stacking in a Bis-perylene Diimide Macrocycle.

This work showcases chiral complementarity in aromatic stacking interactions as an effective tool to optimize the chiroptical and electrochemical properties of perylene diimides (PDIs). PDIs are a notable class of robust dye molecules and their rich photo- and electrochemistry and potential chirality make them ideal organic building blocks for chiral optoelectronic materials. By exploiting the new bay connectivity of twisted PDIs, a dynamic bis-PDI macrocycle (the “Pink Box”) is realized in which homochiral PDI–PDI π–π stacking interactions are switched on exclusively. Using a range of experimental and computational techniques, we uncover three important implications of the macrocycle’s chiral complementarity for PDI optoelectronics. First, the homochiral intramolecular π–π interactions anchor the twisted PDI units, yielding enantiomers with half-lives extended over 400-fold, from minutes to days (in solution) or years (in the solid state). Second, homochiral H-type aggregation affords the macrocycle red-shifted circularly polarized luminescence and one of the highest dissymmetry factors of any small organic molecule in solution (glum = 10–2 at 675 nm). Finally, excellent through-space PDI–PDI π-orbital overlap stabilizes PDI reduced states, akin to covalent functionalization with electron-withdrawing groups.

Nitric-Oxide-Releasing aza-BODIPY: A New Near-Infrared J-Aggregate with Multiple Antibacterial Modalities.

The development of near-infrared (NIR) J-aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine-containing aza-BODIPY precursor (BDP-NH2 ), affording the first nitric oxide (NO)-releasing NIR J-aggregate (BDP-NO). The introduction of N-nitrosamine moieties efficiently inhibits the aromatic interactions of BDP-NH2 , which instead promotes the formation of J-aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents of BDP-NO within micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT-associated inflammation for the in vivo treatment of MRSA infection.

Nitric‐Oxide‐Releasing aza‐BODIPY: A New Near‐Infrared J‐Aggregate with Multiple Antibacterial Modalities

AbstractThe development of near‐infrared (NIR) J‐aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine‐containing aza‐BODIPY precursor (BDP‐NH2), affording the first nitric oxide (NO)‐releasing NIR J‐aggregate (BDP‐NO). The introduction ofN‐nitrosamine moieties efficiently inhibits the aromatic interactions ofBDP‐NH2, which instead promotes the formation of J‐aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents ofBDP‐NOwithin micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT‐associated inflammation for the in vivo treatment of MRSA infection.

Abstract LB516A: The irreversible FLT3 inhibitor FF-10101 is active against a diversity of FLT3 inhibitor resistance mechanisms

Abstract Background: FLT3 tyrosine kinase inhibitors (TKIs) such as midostaurin and gilteritinib have improved clinical outcomes for patients with FLT3-mutant acute myeloid leukemia (AML), but resistance remains a problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 and has shown activity against FLT3 F691L and D835 mutations. We evaluated FF-10101 against an expanded panel of FLT3 resistance mutations and activating mechanisms of MAPK signaling associated with FLT3 TKI resistance in AML cell lines and patient samples. Results: FF-10101 was uniformly active against a series of previously unevaluated FLT3 TKI resistant D835 mutations (sensitivity = IC50 <10X of FLT3-ITD alone in Ba/F3 cells). FF-10101 was more active against F691L than gilteritinib (8-fold vs 14-fold increase in IC50 vs. FLT3-ITD, respectively). K429E and N676K mutations associated with clinical resistance to crenolanib and midostaurin, respectively, were also both FF-10101-sensitive. G697S and Y693N mutations, previously identified by random saturation mutagenesis screening to confer resistance to gilteritinib, also conferred moderate resistance to FF-10101 while Y693C conferred a high degree of resistance to both (IC50 >50X higher than FLT3-ITD). D698N, however, was FF-10101-sensitive and gilteritinib-resistant. Using a cell-based model, we confirmed C695 as the lone residue covalently bound by FF-10101. Moreover, a mutagenesis screen for FF-10101 resistance identified only C695Y/R mutations. Structural modeling showed an aromatic π-π interaction between FF-10101 and Y693 that orients an electrophilic acrylamide portion for covalent bonding of FLT3 at C695, likely explaining resistance conferred by Y693C. Confirmatory mutagenesis experiments showed that Y693F, by recapitulating the native aromatic interaction, retained FF-10101 sensitivity while the non-aromatic Y693S mutation conferred a high degree of resistance. Finally, FF-10101 exerted generally greater cytotoxicity than gilteritinib in FLT3-ITD+ AML cell lines (MOLM-14 and MV4-11) and three FLT3-mutant AML patient samples cultured in HS5 stromal cell conditioned media that models bone marrow microenvironment (BME) induced TKI resistance. In MOLM-14s, FF-10101 more effectively suppressed rebound ERK re-activation after 24h drug exposure than gilteritinib, potentially explaining this enhanced activity. Nevertheless, MOLM-14 and MV4-11s with NRAS G12C and Q61K co-mutations exhibited significant resistance to FF-10101 and gilteritinib. Conclusions: FF-10101 is active against nearly all mutations associated with FLT3 TKI resistance except for C695 mutations (site of FF-10101 binding) and the gilteritinib/crenolanib-resistant Y693C mutation (which has yet to be identified clinically). FF-10101 potentially overcomes resistance associated with the BME but likely remains vulnerable to RAS activating mutants. In report of phase 1 study of FF-10101 in relapsed/refractory AML (NCT03194685), 8/30 evaluable patients exhibited response (27%) with five responding patients previously receiving a FLT3 TKI, including one CRi after progression on gilteritinib. These results and our findings show that FF-10101 has potential to benefit AML patients that acquire certain FLT3 TKD resistance mutations or exhibit progression with other FLT3 TKIs, including gilteritinib. Citation Format: Timothy T. Ferng, Daisuke Terada, Makoto Ando, Theodore C. Tarver, Fihr Chaudhary, Kimberly C. Lin, Aaron C. Logan, Catherine C. Smith. The irreversible FLT3 inhibitor FF-10101 is active against a diversity of FLT3 inhibitor resistance mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB516A.

Maclurin Exhibits Antioxidant and Anti-Tyrosinase Activities, Suppressing Melanogenesis.

Maclurin is rich in some edible fruits such as Morus alba (white mulberry) and Garcinia mangostana. Although maclurin showed anti-cancer and antioxidant effects, its roles in ultraviolet (UV)-induced melanogenesis have not been studied. Here, we investigated the effects of maclurin in melanogenesis using skin cells and a three-dimensional human skin model. When the cytotoxicity of maclurin was examined in B16F10 cells, no cytotoxicity was found up to 20 μM. Maclurin suppressed UVB-mediated tyrosinase activation and melanin accumulation in B16F10 cells without changes in mRNA levels of melanogenesis-related genes including tyrosinase, TRP1, TRP2, CREB, and MITF. Moreover, maclurin reduced melanin contents in melan-a cells, a cell line for normal melanocytes. When applied to a human skin model consisting of the epidermis and melanocytes, maclurin significantly reduced UVB-induced melanin accumulation (~47%) in a concentration-dependent manner based on microscopic observation and Fontana-Masson staining. Protein–ligand docking simulation followed by binding residue analysis showed that maclurin may bind to inactivate tyrosinase by forming multiple hydrogen bonds and hydrophobic and aromatic interactions with the residues of tyrosinase. Together, our study suggests that maclurin may be applied as an anti-melanogenic agent.

Structural basis for altered positional specificity of 15-lipoxygenase-1 with 5S-HETE and 7S-HDHA and the implications for the biosynthesis of resolvin E4

Human 15-lipoxygenases (LOX) are critical enzymes in the inflammatory process, producing various pro-resolution molecules, such as lipoxins and resolvins, but the exact role each of the two 15-LOXs in these biosynthetic pathways remains elusive. Previously, it was observed that h15-LOX-1 reacted with 5S-HETE in a non-canonical manner, producing primarily the 5S,12S-diHETE product. To determine the active site constraints of h15-LOX-1 in achieving this reactivity, amino acids involved in the fatty acid binding were investigated. It was observed that R402L did not have a large effect on 5S-HETE catalysis, but F414 appeared to π−π stack with 5S-HETE, as seen with AA binding, indicating an aromatic interaction between a double bond of 5S-HETE and F414. Decreasing the size of F352 and I417 shifted oxygenation of 5S-HETE to C12, while increasing the size of these residues reversed the positional specificity of 5S-HETE to C15. Mutants at these locations demonstrated a similar effect with 7S-HDHA as the substrate, indicating that the depth of the active site regulates product specificity for both substrates. Together, these data indicate that of the three regions proposed to control positional specificity, π−π stacking and active site cavity depth are the primary determinants of positional specificity with 5S-HETE and h15-LOX-1. Finally, the altered reactivity of h15-LOX-1 was also observed with 5S-HEPE, producing 5S,12S-diHEPE instead of 5S,15S-diHEPE (aka resolvin E4 (RvE4). However, h15-LOX-2 efficiently produces 5S,15S-diHEPE from 5S-HEPE. This result is important with respect to the biosynthesis of the RvE4 since it obscures which LOX isozyme is involved in its biosynthesis. Future work detailing the expression levels of the lipoxygenase isoforms in immune cells and selective inhibition during the inflammatory response will be required for a comprehensive understanding of RvE4 biosynthesis.

Chain-Shattering Polymers as Degradable Microdispersive Solid-Phase Extraction Sorbents.

A chain-shattering polymer (CSP) has been proposed as a microdispersive solid-phase extraction (μdSPE) sorbent in a proof-of-concept study of degradable materials for analytical purposes. The responsive CSP was synthesized from 1,3,5-tris(bromomethyl)-2-nitrobenzene acting as the self-immolative trigger responsive unit and 2,6-naphthalenedicarboxylic acid as aromatic linker to enhance noncovalent aromatic interactions with the analytes. The CSP was characterized and applied as a μdSPE sorbent of a group of plasticizers, which were selected as model analytes, from different types of environmental water samples (tap, waste, and spring waters). Gas chromatography coupled to mass spectrometry detection was used for analyte determination. Mean recovery values were in the range of 80%–118% with RSD values below 22%. After the extraction, the polymer could be efficiently degraded by UV irradiation or by chemical reduction, recovering the aromatic linker. This work has proved the potential of CSPs as recyclable sorbents, paving the way to more environmentally benign analytical procedures.

The enthralling effect of packing on the light emission of pyridazinone based luminophore: Crystallographic, electronic absorption and computational studies

The present study unfolds the synthesis and characterization of a new butylidine linked hetero dimer of pyridazinone (PNP). The crystal structure analysis of PNP reveals that it exhibited infinite 1D linear chains connected through C-H∙∙∙O interaction and interlayer connectivity was supported by the unconventional orthogonal dipolar interaction via nitro-aromatic (ONO2···π(C)Ar). These interactions are also described using DFT calculations and are potentially studied. Here we discuss the influence of crystal structure on the photophysical properties of a new solid state emitter containing brick layer packing. Furthermore, we conducted detailed exploration of the intermolecular interactions that maintain the crystal packing of the structure by employing the Hirshfeld surface analysis and its corresponding two-dimensional fingerprint plots revealing that the C-H∙∙∙O interaction mainly stabilized the crystal structure. Time-dependent density functional theory (TDDFT) studies and observed nitro aromatic interactions (ONO2∙∙∙(C)Ar) in the crystal helped to explain the electronic behaviour of PNP. The validity of the computations is supported by a good agreement between the estimated and experimental values of the excitation energy transfer. Furthermore, we conducted detailed research on the Hirshfeld surface analysis and the intermolecular interactions that stabilize the crystal packing using their corresponding two-dimensional fingerprint plot. Some standard thermodynamical parameters such as specific heat, entropy and free energy have also been computed. In addition to this, the variation of specific heat with temperature has been explored.

Synthesis and crystal structure of rac-2-(1,3-dioxo-isoindolin-2-yl)ethyl 4-methyl-N-phenyl-N'-(tri-iso-propyl-sil-yl)benzene-sulfondiimidoate: the first member of a new substance class.

The title compound {systematic name: rac-2-[7-methyl-4-(4-methylphenyl)-4-(phenylimino)-6,6-bis(propan-2-yl)-3-oxa-4λ6-thia-5-aza-6-silaoct-4-en-1-yl]-2,3-dihydro-1H-isoindole-1,3-dione}, C32H41N3O3SSi, was synthesized by desoxychlorination of 4-methyl-N-phenyl-N'-(triisopropyl-sil-yl)benzene-sul-fon-imid-am-ide and subsequent reaction with 2-(2-hy-droxy-eth-yl)isoindoline-1,3-dione. The racemic compound was crystallized from isopropanol. The structural characterization by single-crystal X-ray diffraction revealed two double-bonded nitro-gen atoms to the central sulfur atom and an overall crystal packing driven by its aromatic inter-actions.

Effects of the Cationic Structure on the Adsorption Performance of Ionic Polymers toward Au(III): an Experimental and DFT Study.

Ionic polymers have been proven to be promising adsorbents in recovering Au(III) due to their advantages of simple synthesis and high adsorption efficiency. However, the unclarity of the relationship between the adsorption ability of ionic polymers and their cationic structures hinders further optimization of their adsorption performance. This study synthesized a series of ionic polymers with pyridinium, imidazolium, piperidinium, pyrrolidinium, and triethylammonium cations to discover the effects of the cationic structure on their adsorption properties. Experimental results show that the existence of anion-π interaction between aromatic cations and [AuCl4]- makes the aromatic cations-anion interaction stronger, which does not enhance the adsorption performance of the aromatic-based ionic polymer. This is due to the charge delocalization in the aromatic ring, resulting in a lower electrostatic potential (ESP) of aromatic cations than that of aliphatic cations with a localized charge. The higher the ESP of cations, the better the adsorption performance of the corresponding ionic polymer. This study serves as a deep understanding of the cationic structure-adsorptive performance relationship of the ionic polymer at the molecular level and further provides a theoretical guidance to optimize the adsorption performance of ionic polymers.

Methionine‐aromatic Interaction as a Tool to Enhance Protein Stability

Nonbonded aromatic interactions play a significant role in stabilizing a folded protein structure(1, 2). Apart from well‐studied aromatic‐aromatic interactions in proteins, preferential proximity of sulfur containing cysteine and methionine sidechains and aromatic rings is also observed in protein hydrophobic cores and at the interfaces of protein‐protein complexes. Methionine‐aromatic motifs are examples of such S‐aromatic motifs that provide additional stabilization at a longer distance range over pure hydrophobic interactions(3). Although the idea of preferential association of aromatic amino acids has been successfully implemented for de novo design of peptides and proteins, the additional stability provided by met‐aromatic motif over pure hydrophobic interaction and its potential significance in designing a stabler protein fold has not been examined before. The present work shows the relevance of S‐aromatic interaction in increasing thermodynamic stability of a protein fold using Small Ubiquitin‐Like Modifier (SUMO) protein. We found that a highly conserved methionine‐phenylalanine motif in the core is a unique signature of SUMO but absent in other homologous Ubiquitin‐like (Ubl) protein folds. Using biophysical measurements and solution NMR based experiments, we found that the specific ‘up’ conformation between the methionine‐phenylalanine pair is critical to SUMO’s β‐grasp fold stability and its function(4). Given the additional stability provided by met‐aromatic motif over classical hydrophobic interaction, we engineered new S‐aromatic motifs in SUMO by replacing phenylalanine with other naturally occurring aromatic amino acids. Combining all atom MD simulations and solution NMR studies, we identify the energetically preferred interaction geometry of different met‐aromatic motifs inside the core. We found that the engineered SUMOs with increasing S‐aromatic interaction strength enhances the overall protein stability. Overall, our results reveal the potential role of S‐aromatic interactions as a design tool in enhancing thermodynamic stability of a protein fold.