Side-chain Groups Research Articles

Multifunctional Fluorescent Main-Chain Charged Polyelectrolytes Synthesized by Cascade C-H Activation/Annulation Polymerizations.

Fluorescent polyelectrolytes have attracted enormous attention as functional polymer materials. In contrast with the widely studied conjugated polyelectrolytes with ionic groups in side chains, fluorescent main-chain charged polyelectrolytes (MCCPs) have rarely been explored due to the large synthetic difficulty. Herein, we develop a facile and atom-economical N-heterocyclic carbene-directed cascade C-H activation/annulation polymerization strategy that can transform readily available imidazolium substrates and internal diynes into multifunctional fluorescent MCCPs with complex structures and high molecular weights (absolute Mn up to 135 600) in nearly quantitative yields. The presence of multisubstituted polycyclic N-heteroaromatic cations in polymer backbones endow the obtained MCCPs with excellent solution processability, high thermal stability, and dual-state efficient fluorescence in both solution and aggregate states. Benefiting from the strong electron-withdrawing capability of the cationic heterocycles in main chains, multicolored aggregate-state fluorescence can be readily achieved by modifying the substituents around the cationic ring-fused core. Taking advantage of the good photosensitivity of the fluorescent MCCP thin films, multiscale and high-resolution fluorescent photopatterns with different colors can be facilely prepared with potential applications in optical display devices and anticounterfeiting systems. Moreover, the strong electrostatic interactions of these cationic MCCPs with anionic polyelectrolytes enable them to form multicolored fluorescent interfacial polyelectrolyte complexation microfibers with directly visualized internal structures. Such flexible microfibers can be further made into diversified forms of fiber-based macroscopic patterns or painting.

Novel Alcohol-Soluble Nitroxide Radical Conjugated Polymer for Cathode Modifier of Efficient Organic Solar Cells with Enhanced Stability.

Alcohol-soluble conjugated polymers with polar side-chain components have been regarded as one of the most promising cathode interfacial modifers (CIMs) to achieve high-performance organic solar cells (OSCs). Herein, a novel alcohol-soluble nitrogen oxide radical conjugated polymer (PBN-NO) containing dimethylamine groups for regulating metal work function and the dangling of 2,2,6, 6-tetramethylpiperidine 1-oxy (TEMPO) radical side-chain groups for theoretically improving the conductivity, was prepared and characterized. As compared to the OSCs from PM6:Y6 blends with the most common CIMs of PFN, PDINO, and PDINN, the OSCs with PBN-NO as CIMs provide better or comparable power conversion efficiencies (PCEs) (16.19% vs 13.10%, 15.60%, and 16.15%), enhanced photostability, and thermal stability. Besides that, the reasons for the improving PCEs of the OSCs with PBN-NO modifier are systematically investigated and supported by a set of comparative experiments such as exciton dissociation, charge recombination, capacitance-voltage (C-V), etc. To the best of our knowledge, this is the first report of an alcohol-soluble nitroxide radical conjugated polymer that successfully integrates the interfacial modification of polar groups and improves conductivity by dangling radicals, therefore contributing to efficient OSCs with enhanced stability.

Interaction of Positively Charged Oligopeptides with Blood Plasma Proteins.

In this project, we combine two areas of research, experimental characterization and molecular docking studies of the interaction of positively charged oligopeptides with crucial blood plasma proteins. The investigated peptides are rich in NH2 groups of amino acid side chains from Dap, Orn, Lys, and Arg residues, which are relevant in protein interaction. The peptides are 9- and 11-mer with the following sequences: (Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt), (Lys-Dab-Ala-Gly-Orn-Pro-His-Lys-Arg), and (Lys-Dab-Dab-Gly-Orn-Pro-Phe(2-F)-Lys-Arg). The net charge of the compound strongly depends on the pH environment and it is an important aspect of protein binding. The studied oligopeptides exhibit therapeutic properties: anti-inflammatory activity and the capacity to diminish reactive oxygen species (ROS). Therefore, the mechanism of potential binding with blood plasma components is the next challenge. The binding interaction has been investigated under pseudo-physiological conditions with the main blood plasma proteins: albumin (BSA), α1-acid glycoprotein (AAG), and γ-globulin fraction (GGF). The biomolecular quenching constant (kq) and binding constant (Kb) were obtained by fluorescence spectroscopy at various temperatures. Simultaneously, the changes in the secondary structure of proteins were monitored by circular dichroism (CD) and infrared spectroscopy (IR) by quantity analysis. Moreover, molecular docking studies were conducted to estimate the binding affinity, the binding domain, and the chemical nature of these interactions. The results show that the investigated oligopeptides could be mainly transported by albumin, and the binding domain I is the most favored cavity. The BSA and GGF are able to form stable complexes with the studied compounds as opposed to AAG. The binding reactions are spontaneous processes. The highest binding constants were determined for Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt peptide, in which the values of the binding constants Kb to BSA and GGF were 10.1 × 104 dm3mol-1 and 3.39 × 103 dm3mol-1, respectively. The positively charged surface of peptides participated in salt bridge interaction with proteins; however, hydrogen bonds were also formed. The secondary structure of BSA and GGF after contact with peptides was changed. A reduction in the α-helix structure was observed with an increase in the β-sheet and β-turn and random coil structures.

A single amino acid substitution alters activity and specificity in Plasmodium falciparum aspartyl & asparaginyl-tRNA synthetases.

The specificity of each aminoacyl-tRNA synthetase (aaRS) for its cognate amino acid ensures correct tRNA esterification and allows fidelity in protein synthesis. The aaRSs discriminate based on the chemical properties of their amino acid substrates and structural features of the binding pockets. In this study, we characterized aspartyl-(DRS) and asparaginyl-tRNA synthetase (NRS) from Plasmodium falciparum to determine the basis of their specificity towards L-asp and L-asn respectively. The negatively charged L-asp and its analogue L-asn differ only in their side-chain groups i.e., -OH and -NH2. Further, the amino acid binding sites are highly conserved within these two enzymes. Analysis of the substrate (L-asp/L-asn) binding sites across species revealed two highly conserved residues in PfDRS (D408 and K372) and PfNRS (E395 and L360) that are involved in recognition of the Oδ2/Nδ2 of L-asp/L-asn respectively. These residues were mutated and swapped between the D408→E in PfDRS and the corresponding E395→D in PfNRS. A similar approach was employed for residue number K372→L in PfDRS and L360→K in PfNRS. The mutated PfDRSD408E retained its enzymatic activity during step 1 of aminoacylation reaction towards L-asp and L-asn and esterified tRNAAsp with L-asp like wild type enzyme, while the PfDRSK372L was rendered enzymatically inactive. The correspondingly mutated PfNRSE395D was enzymatically inactive. The mutated PfNRSL360K had an altered specificity and esterified tRNAAsn with non-cognate amino acid L-asp and not L-asn. These data suggest that the residue K372 is crucial for the enzymatic activity of PfDRS while the residue L360 in PfNRS imparts specificity towards L-asn.

Rhamnogalacturonan-I as a nematode chemoattractant from Lotus corniculatus L. super-growing root culture.

The soil houses a tremendous amount of micro-organisms, many of which are plant parasites and pathogens by feeding off plant roots for sustenance. Such root pathogens and parasites often rely on plant-secreted signaling molecules in the rhizosphere as host guidance cues. Here we describe the isolation and characterization of a chemoattractant of plant-parasitic root-knot nematodes (Meloidogyne incognita, RKN). The Super-growing Root (SR) culture, consisting of excised roots from the legume species Lotus corniculatus L., was found to strongly attract infective RKN juveniles and actively secrete chemoattractants into the liquid culture media. The chemo-attractant in the culture media supernatant was purified using hydrophobicity and anion exchange chromatography, and found to be enriched in carbohydrates. Monosaccharide analyses suggest the chemo-attractant contains a wide array of sugars, but is enriched in arabinose, galactose and galacturonic acid. This purified chemoattractant was shown to contain pectin, specifically anti-rhamnogalacturonan-I and anti-arabinogalactan protein epitopes but not anti-homogalacturonan epitopes. More importantly, the arabinose and galactose sidechain groups were found to be essential for RKN-attracting activities. This chemo-attractant appears to be specific to M. incognita, as it wasn't effective in attracting other Meloidogyne species nor Caenorhabditis elegans. This is the first report to identify the nematode attractant purified from root exudate of L corniculatus L. Our findings re-enforce pectic carbohydrates as important chemicals mediating micro-organism chemotaxis in the soil, and also highlight the unexpected utilities of the SR culture system in root pathogen research.

Molecular Recognition of Imidazole-Based Drug Molecules by Cobalt(III)- and Zinc(II)-Coproporphyrins in Aqueous Media.

The methods of 1H NMR, spectrophotometric titration, mass spectrometry and elemental analysis are applied to determine the selective binding ability of Co(III)- and Zn(II)-coproporphyrins I towards a series of imidazole-based drug molecules with a wide spectrum of pharmacological activity (metronidazole, histamine, histidine, tinidazole, mercazolil, and pilocarpine) in phosphate buffer (pH 7.4) simulating the blood plasma environment. It is shown that in aqueous buffer media, Co(III)-coproporphyrin I, unlike Zn(II)-coproporphyrin I, binds two imidazole derivatives, and the stability of mono-axial Co-coproporphyrin imidazole complexes is two to three orders of magnitude higher than that of similar complexes of Zn-coproporphyrin I. The studied porphyrinates are found to have the highest binding ability to histamine and histidine due to the formation of two additional hydrogen bonds between the carboxyl groups of the porphyrinate side chains and the binding sites of the ligands in the case of histidine and a hydrogen bond between the amino group of the ligand and the carbonyl oxygen atom of the carboxyl group of the porphyrinate in the case of histamine. The structures of the resulting complexes are optimized by DFT quantum chemical calculations. The results of these studies may be of use in the design of biosensors, including those for the detection, control and verification of various veterinary drug residues in human food samples.

Improving C2H3Cl2F hydrate formation for cold storage in the presence of amino acids

The motivation of this study is to investigate the effect of side chain groups of amino acids on hydrate formation. To confirm their effects on hydrate nucleation and growth, we use aromatic amino acids (tryptophan, phenylalanine, tyrosine), heterocyclic amino acids (histidine, proline) and aliphatic acids (arginine, alanine) as biological additives. The effect of different side chain groups of amino acids on hydrate formation kinetics is investigated. It is found that the hydrophobic groups of amino acids have a significant influence on promoting hydrate formation compared with the hydrophilic groups. Among the hydrophobic groups, aromatic groups are superior to aliphatic groups in improving hydrate nucleation and growth rate, while aliphatic groups are more advantageous in increasing hydrate production, cold storage capacity (CSC) and hydrate conversion rate. Heterocyclic amino acids have no obvious effect on hydrate formation. In addition, foam is not produced during hydrate dissociation, which is good for practical application.

Fmoc-SPPS-compatible p-methoxyphenacyl-modified glutamic for the synthesis of photocaged peptides

The development of photocaged glutamic acid (Glu) contributes to the time-resolved control of peptide and protein activities. Here, we efficiently synthesized the Glu with the side chain modified by photosensitive p-methoxyphenacyl group. This photocaged Glu can be introduced into peptide through standard 9‑fluorenylmethoxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS), and can be re-exposed the Glu side-chain carboxy group by removing the photosensitive group under light irradiation. We prepared caged Endothelin-1 (ET-1) analogues with p-methoxyphenacyl-modified Glu and successfully achieved decaging.

Electrocatalytic behavior of amino compound oxidation on NiCo catalyst and energy conversion

Direct electricity is generated from amino compounds with different side chain groups via electrooxidation on a NiCo catalyst.

Effects of food formulation on bioavailability of phytosterols: phytosterol structures, delivery carriers, and food matrices.

Daily intake of phytosterols (PSs) as a diet supplement can lower blood-cholesterol levels and reduce the risks of cardiovascular diseases. However, the high crystallinity, low water solubility, easy oxidizability, and other characteristics of PSs restrict their application and bioavailability in food products. The formulation parameters including the structures of PSs, delivery carriers, and food matrices may play an important role in the release, dissolution, transport, and absorption of PSs in functional foods. In this paper, the effects of formulation parameters, including phytosterol structures, delivery carriers, and food matrices, on the bioavailability of phytosterols are summarized and suggestions are provided for the formulation design of functional foods. The side chain and hydroxyl esterification group of PSs may significantly affect their lipid or water solubilities and micellization capacities, which in turn affect the bioavailability of PSs. Selecting suitable delivery carriers based on the characteristics of the food system can reduce the crystallinity and oxidation of PSs and control the release of PSs, thereby improving the PS stability and delivery efficiency. Moreover, the ingredients of the carriers or food products would also influence the release, solubility, transport, and absorption of PSs in the gastrointestinal tract (GIT).

4-Electron redox enabled by a perylene diimide containing side-chain amines for efficient organic cathode development.

A perylene diimide containing side-chain amines (PDIN) was studied as an organic cathode for application in lithium batteries, showing a high capacity of 174 mA h g-1. The chemical structures, experimental results, and calculation analyses verify that PDIN performed a 4-electron redox reaction jointly involving its CO and side-chain amine groups. This study promotes the development of organic cathodes with multi-electron redox reactions.

Rational design of non-fullerene acceptors via side-chain and terminal group engineering: a computational study.

We investigated the optoelectronic and photovoltaic properties of three types of acceptor-donor-acceptor-based non-fullerene acceptor (NFA) molecules for organic solar cell (OSC) applications. Density functional theory and its time-dependent variant were employed to compute the quadrupole moment perpendicular to the π-system (Q20), open circuit voltage (VOC), and other relevant solar cell parameters. The role of functionalization in the acceptor unit on the overall device performance was explored by incorporating halogen and methoxy-based electron-withdrawing groups. The electronegativity differences between the halogen atoms and the methoxy group demonstrated contrasting effects on the energy levels, molecular orbitals, and absorption maximum. We observed a trade-off between short-circuit current (JSC) and VOC, which was further substantiated by an inverse correlation between Q20 and VOC. We found an optimum value of Q20 in the range of 80 to 130 ea02 to achieve an optimized solar cell performance. Among the designed systems, Se-derived NFAs with a small band gap, red-shifted absorption maximum, high-oscillator strength, small exciton binding energy, and optimum Q20 turned out to be potential candidates for future applications. These criteria can be generalized to design and screen next-generation non-fullerene acceptors to achieve improved OSC performance.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Synthesis of disulfide-rich C-terminal Cys-containing peptide acids through a photocleavable side-chain anchoring strategy.

A side-chain anchoring strategy has been developed as an effective method for the synthesis of C-terminal Cys-containing peptide acids. However, the application of this strategy to CCAs containing more than one disulfide bond is still hindered due to the trifluoroacetic acid (TFA) lability of the anchored side-chain groups. Herein, we report a photocleavable side-chain anchoring strategy using newly developed molecules having photocleavable side-chain protecting groups that are stable against TFA cleavage to assist in the formation of disulfide bonds. The utility of this new strategy was demonstrated by the synthesis of Riparin 1.1 and hCNP22 containing one disulfide bond and α-conotoxin Vc1.1 containing two disulfide bonds. This new strategy will provide new possibilities for the synthesis of disulfide-rich C-terminal Cys-containing peptide acids.

Cell-Penetrating Dabcyl-Containing Tetraarginines with Backbone Aromatics as Uptake Enhancers.

Cell-penetrating peptides represent an emerging class of carriers capable of effective cellular delivery. This work demonstrates the preparation and investigation of efficient CPPs. We have already shown that the presence of 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) and Trp greatly increase the uptake of oligoarginines. This work is a further step in that direction. We have explored the possibility of employing unnatural, aromatic amino acids, to mimic Trp properties and effects. The added residues allow the introduction of aromaticity, not as a side-chain group, but rather as a part of the sequence. The constructs presented exceptional internalization on various cell lines, with an evident structure-activity relationship. The CPPs were investigated for their entry mechanisms, and our peptides exploit favorable pathways, yet one of the peptides relies highly on direct penetration. Confocal microscopy studies have shown selectivity towards the cell lines, by showing diffuse uptake in FADU cells, while vesicular uptake takes place in SCC-25 cell line. These highly active CPPs have proved their applicability in cargo delivery by successfully delivering antitumor drugs into MCF-7 and MDA-MB-231 cells. The modifications in the sequences allow the preparation of short yet highly effective constructs able to rival the penetration of well-known CPPs such as octaarginine (Arg8).

Does Urea Preferentially Interact with Amide Moieties or Nonpolar Sidechains? A Question Answered Through a Judicious Selection of Model Systems.

The transfer model suggests that urea unfolds proteins mainly by increasing the solubility of the amide backbone, probably through urea-induced increase in hydrogen bonding. Other studies suggest that urea addition increases the magnitude of solvent-solute van der Waals interactions, which increases the solubility of nonpolar sidechains. More recent analyses hypothesize that urea has a similar effect in increasing the solubility of backbone and sidechain groups. In this work, we compare the effects of urea addition on the solvation of amides and alkyl groups. At first, we study the effects of urea addition upon solvent hydrogen bonding acidity and basicity through the perturbation in the fluorescence spectrum of probes 1-AN and 1-DMAN. Our results demonstrate that the solvent's hydrogen bonding properties are minimally affected by urea addition. Subsequently, we show that urea addition does not perturb the intra-molecular hydrogen bonding in salicylic acid significantly. Finally, we investigate how urea preferentially interacts with amide and alkyl groups moieties in water by comparing the effects of urea addition upon the solubility of acetaminophen and 4-tertbutylphenol. We show that urea affects amide and t-butyl solubility (lowers the transfer free energy of both amide (backbone) and alkyl (sidechain) groups) in a similar fashion. In other words, preferential interaction of urea with both moieties contributes to protein denaturation.

Synthesis and Mesomorphic Properties of Biphenyl Derivatives with Central Unit Based on 1,6-Hexamethylene Diisocyanate Oligomers

A number of compounds with biphenyl as a mesogenic fragment and a structure simulating LC dimers, polymers with mesogenic side chain groups and a star-shaped structure have been synthesized. An approach for the synthesis of such compounds under mild conditions and without a complex purification procedure with a quantitative yield, has been developed. The approach is the implementation of “click chemistry” methods for the synthesis of LC compounds. It has been shown that the LC state is observed only if there are three biphenyls in one molecule, i.e., the compounds appear to be similar to polyesters with biphenyl as a mesogenic moiety. The determining factor in the formation of the LC state and particularly smectic mesomorphism of compounds with such a potentially “weak” mesogen as biphenyl is the formation of intermolecular hydrogen bonds.

Three segment ligation of a 104 kDa multi-domain protein by SrtA and OaAEP1

NMR spectroscopy is an excellent tool for studying protein structure and dynamics which provides a deeper understanding of biological function. As the size of the biomolecule of interest increases, it can become advantageous to dilute the number of observed signals in the NMR spectrum to decrease spectral overlap and increase resolution. One way to limit the number of resonances in the NMR data is by selectively labeling a smaller domain within the larger macromolecule, a process called segmental isotopic labeling. Many examples of segmental isotopic labeling have been described where two segments of a protein are ligated together by chemical or enzymatic means, but there are far fewer descriptions of a three or more segment ligation reaction. Herein, we describe an enzymatic segmental labeling scheme that combines the widely used Sortase A and more recently described OaAEP1 for a two site ligation strategy. In preparation to study proposed long-range allostery in the 104 kDa DNA damage repair protein Rad50, we ligated side-chain methyl group labeled Zn Hook domain between two long segments of otherwise unlabeled P.furiosus Rad50. Enzymatic activity data demonstrated that the scars resulting from the ligation reactions did not affect Rad50 function within the Mre11-Rad50 DNA double strand break repair complex. Finally, methyl-based NMR spectroscopy confirmed the formation of the full-length ligated protein. Our strategy highlights the strengths of OaAEP1 for segmental labeling, namely faster reaction times and a smaller recognition sequence, and provides a straightforward template for using these two enzymes in multisite segmental labeling reactions.

Utility of methyl side chain probes for solution NMR studies of large proteins

Selective isotopic labeling of methyl side chain groups in proteins and other biomolecules, combined with advances in perdeuteration, new pulse sequences, and high field spectrometers with cryogenic probes, has revolutionized the field of solution nuclear magnetic resonance (NMR) spectroscopy by enabling characterization of macromolecular systems with molecular weights above 1 MDa in their native aqueous environment. This tutorial provides a basic overview for how modern NMR spectroscopists can utilize methyl side chain probes to study their system of interest. The advantages and limitations of methyl side chain probes are discussed. In addition, the preparation of selectively 13C-methyl labeled recombinant protein samples, strategies for manual and automated methyl NMR resonance assignment, and the application of methyl probes for characterization of dynamics and conformational exchange are discussed. A sneak preview for ways in which methyl probes are expected to continue to advance the field of biomolecular NMR towards new horizons in solution studies of large supramolecular complexes is also presented.

The change of amino acids samples under metalimnetic oxygen minimum condition: Characterization and mechanism

The metalimnetic oxygen minimum (MOM) is a common anaerobic phenomenon that occur between 5.00 and 40.00 m of reservoirs. Amino acids (AAs) are widely found in water, but their change in MOM remain unclear. In this study, four AAs with different side chain groups were selected to explore the change of their samples and related disinfection by-products formation potential (DBPFPs) under MOM condition. The results showed that the final degradation rate of dissolved organic carbon and dissolved organic nitrogen of four AAs samples were 11.71%−59.87% and 26.50%−100.00% under MOM condition. Aspartic acid samples were the easiest to be degraded, whereas glycine samples were the opposite. While the total fluorescence intensity increased by 6.30%−113.40% for the appearance of tryptophan-like substance. The total DBPFPs of glutamic acid, arginine and aspartic acid samples were finally decreased by 4.73%, 8.00% and 98.88% (glycine sample increased by 2.30 times). Compared with the surface condition, the degradation of AAs samples and the change of DBPFPs were significantly inhibited under MOM condition. In addition, the diversities of bacterial communities were significantly reduced under MOM condition, which was very unfavorable to the degradation of AAs samples, and in turn affected the control of DBPs and deteriorated the water quality.