Functional Side Chains Research Articles

Liquid/liquid interfacial cross-linking reaction of conjugated polymer prepared cross-linked films with improved electrochromic and capacitance properties

Interfacial crosslinking is a useful and unique method for preparing films with desired structures. Here, a crosslinked structure film (Rc-mProdot) is obtained from the linear polymer (mProdot) with cross-linkable functional side-chains via the liquid/liquid interfacial crosslinking. Transmission phenomenon and Tyndall effect reflected the assembling progress of Rc-mProdot film. FT-IR and SEM data prove the formation of the desired cross-linked polymer film with loose structure precisely. Significantly, the desirable Rc-mProdot film not only retains the original color and similar electrochemical behaviors to these of the spin-coated mProdot polymer film, but also exhibits improved electrochromic and capacitance properties including a faster electrochromic discoloring time (0.26 s), larger capacitance (increasing by 60% than Rc-mProdot film) and a better charge-discharge stability (retaining 79.1% after 600 cycles). This work provides a simple and efficient approach to liquid/liquid interfacial Schiff-base reaction to construct conjugated polymer films with loose structure towards improving electrochromic and supercapacitor performance and applications.

Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water.

The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pKa primary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5–9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as β- and γ-peptides, displays poor selectivity. Notably, this discovery enables the highly α-selective protecting-group-free ligation of lysine peptides at neutral pH while leaving the functional ε-amine side chain intact.

Recent Advances in Post-polymerization Modifications on Polypeptides: Synthesis and Applications.

Polypeptides, a kind of very promising biomaterial, have shown a wide range of applications due to their excellent biocompatibility, easy accessibility, and structural variability. To synthesize polypeptides with desired functions, post-polymerization modification (PPM) plays an important role in introducing novel chemical structure on their side-chains. The key to PPM strategy is to develop highly selective and efficient reactions that can couple the additional functional moieties with pre-installed side-chain functionalities on polypeptides. In this minireview, classic PPM approaches and their recent progresses are summarized and categorized into five sections, including various reactions on unsaturated alkyl, oxygen-, nitrogen-, sulfur-containing and other special functional groups. In addition, we also highlight the applications of the resultant structure-diversified polypeptides in the field of biomaterial.

Controllable Polymerization of N -Substituted β-Alanine N -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

Controllable Polymerization of <i>N</i> -Substituted β-Alanine <i>N</i> -Thiocarboxyanhydrides for Convenient Synthesis of Functional Poly(β-peptoid)s

A mussel-pearl side chain interaction in mercury(II) and phenol removal by sulfur-functionalized covalent organic frameworks: A DFT study

The covalent organic framework materials (COFs) with excellent chemical and physical characteristics have been rapidly developed as adsorbents in the application of environmental remediation. In the design of COFs, the selection of functional groups and side chains is of great significance. Herein, density function theory (DFT) method is used to illustrate the adsorption behavior and mechanism of three sulfur-functionalized COFs (S-COFs) for the adsorption of mercury(II) and phenol. According to the analysis of geometric configurations and electronic properties, it demonstrated that the side chains of S-COFs with high flexibility and concentrated sulfur-functional groups, acting like a closed mussel which tightly confined the contaminants, the highest adsorption was −24.32 kcal/mol. The adsorption mechanism of phenol and mercury(II) on S-COFs was elucidated. For phenol, hydrogen bonds and π-π stacking interaction played an important role in the adsorption process, while the coordination interaction was dominated for the adsorption of mercury(II). This research explains the importance of selecting appropriate functional groups and side chains for COFs in the removal of contaminants in the molecular scale, and reveals the great potential of COFs in environmental remediation applications.

New poly(ether-phosphoramide)s sulfides based on green resources as sensitive films for the specific impedimetric detection of nickel ions

For the development of selective and sensitive chemical sensors, we have developed a new family of poly(ether-phosphoramide) polymers. These polymers were obtained with satisfactory yields by nucleophilic aromatic polycondensation using isosorbide as green resources, and bisphenol A with two novel difluoro phosphinothioic amide monomers. Unprecedented, the thiophosphorylated aminoheterocycles monomers, functionalized with two heterocyclic amine, N-methylpiperazine and morpholine were successfully obtained by nucleophilic substitution reaction of P(S)–Cl compound. The resulting polymers were characterized by different analytical techniques (NMR, MALDI–ToF MS, GPC, DSC, and ATG). The resulting partially green polymers, having tertiary phosphine sulfide with P–N side chain functionalities along the main chain of polymers are the sensitive film at the surface of a gold electrode for the impedimetric detection of Cd, Ni, Pb and Hg. The bio-based poly(ether-phosphoramide) functionalized with N-methylpiperazine modified sensor showed better analytical performance than petrochemical based polymers for the detection of Ni2+. A detection limit of 50 pM was obtained which is very low compared to the previously published electrochemical sensors for nickel detection.

Effects of functional groups and side chains on assembly of “X”-shaped new aggregation-induced emission molecules

The self-assembly properties of aggregation-induced emission molecules play important roles in electroluminescence devices and fluorescence sensors because noncovalent interactions in self-assembly structures would accelerate the excitation energy consumption. However, there are only few studies to explore their self-assembly properties on the interface and there is still a great need for further understanding self-assembled mechanisms from the viewpoint of molecular design. Here, we presented three X-shaped aggregation-induced emission molecules X1, X2 and X3, which decorated with different functional groups and alkyl side chains. The self-assembly structures were revealed by scanning tunneling microscopy technique in combination with density functional theory. Results showed that X-shaped molecules self-assembled into different structures, depending on their molecular structure, especially the functional groups. Furthermore, self-assembly structures could be regulated by adjusting solution concentration. In more detail, parallel with gradually increasing solution concentration, the molecules approached closer and molecule–molecule interactions were enhanced, finally resulting in new nanostructures. The self-assembly properties of three X-shaped aggregation-induced emission molecules on the liquid/solid interface would give a guidance for further exploring the aggregation state in three-dimensional space. Meanwhile, the two-dimensional nanostructures might show special properties, which could be used in fabricating next generation functional films.

Targeting G-Quadruplex DNA for Cancer Chemotherapy.

The self-association of DNA formed by Hoogsteen hydrogen bonding comprises several layers of four guanine or G-tetrads or G4s. The distinct feature of G4s, such as the G-tetrads and loops, qualify structure-selective recognition by small molecules and various ligands and can act as potential anticancer therapeutic molecules. The G4 selective ligands can influence gene expression by targeting a nucleic acid structure rather than sequence. Telomere G4 can be targeted for cancer treatment by small molecules inhibiting the telomerase activity, whereas c-MYC is capable of controlling transcription and can be targeted to influence transcription. The k-RAS is one of the most frequently encountered oncogenic driver mutations in pancreatic, colorectal, and lung cancers. The k-RAS oncogene plays an important role in acquiring and increasing drug resistance and can also be directly targeted by small molecules to combat k-RAS mutant tumors. Modular G4 ligands with different functional groups, side chains, and rotatable bonds, as well as conformation, affect the binding affinity/ selectivity in cancer chemotherapeutic interventions. These modular G4 ligands act by targeting the diversity of G4 loops and groves and assist in developing more drug-like compounds with selectivity. In this review, we present the recent research on synthetic G4 DNA-interacting ligands as an approach towards the discovery of target-specific anticancer chemotherapeutic agents.

Efficiency enhancement of organic solar cell by small molecule electrolyte based on naphthalene diimide as an electron transport layer

As an electron transport layer (ETL) for organic solar cells (OSCs), a naphthalene diimide (NDI)-based alcohol-soluble small molecule electrolyte (FN-NDI-Br) was designed and synthesized. The small molecule electrolyte was synthesized from the quaternization of the amino-terminal group in the alkyl chain. A bulk heterojunction (BHJ)-based inverted OSCs with the ITO/ZnO/ETL/PTB7-Th:PC71BM/MoO3/Ag structure were fabricated. The power conversion efficiency (PCE) enhancement was achieved by inserting a small molecule electrolyte as the interlayer. The device performance of the device with the PTB7-Th and PC71BM blend as the photoactive layer and FN-NDI with acetic acid additive as ETL was enhanced over the device with pristine ZnO from 8.53% to 8.78%. The performance of the device was enhanced up to 9.16% by modifying the side chain functionality compared with the device with a FN-NDI interlayer.

Direct (hetero)arylation polymerization, electrochemical and optical properties of regioregular 3-substituted polythiophenes with alkylsulphanyl and alkylsulfonyl groups

Regioregular polythiophenes have been widely used in organic semiconducting applications due to their crystallinity and solubility. The alkylsulfanyl and alkylsulfonyl side chains could serve as useful synthetic strategy for adjusting the electronic properties of organic semiconductors. In this paper, head-to-tail coupled and highly regioregular poly(3-octylthiothiophene)s (PTS) and poly(3-octylsulfonylthiophene)s (PTSO2) were synthesized through direct (hetero)arylation polymerization. The head-to-tail (HT) regioregularity of the polymer were determined by the widely used 1H NMR method. The HOMO and LUMO energy levels of poly(3-alkylthiophene) were lowered by adjusting the oxidation state of sulfur from sulfanyl to sulfonyl. The effects of these functional side chains are presented through UV−vis, fluorescence, and electrochemical measurements, as well as crystallographic analysis of these synthetic polymers.

Iterative Synthesis of Stereo- and Sequence-Defined Polymers via Acid-Orthogonal Deprotection Chemistry.

Absolute control over polymer stereo- and sequence structure is highly challenging in polymer chemistry. Here, an acid-orthogonal deprotection strategy is proposed for the iterative synthesis of a family of unimolecular polymers starting with enantiopure serines, featuring precise sequence, stereoconfiguration and side-chain functionalities that cannot be achieved using traditional polymerization techniques. Acid-orthogonal deprotections proceed independently of one another by the selection of protecting groups that feature the respective acid-lability. Under p-toluenesulfonic acid, acidolysis of tert-butyloxycarbonyl can proceed exclusively, while low-dosage trifluoroacetic acid and low temperature only trigger the selective and quantitative cleavage of trityl. The pioneering use of this acid-orthogonal deprotection chemistry increases the compatibility with otherwise sensitive groups and opens up pathways to facilely introduce structural and functional diversity into stereo- and sequence-defined polymers, thus imparting their unique properties beyond natural biopolymers.

Tuneable N‐Substituted Polyamides with High Biomass Content via Ugi 4 Component Polymerization

AbstractUgi 4‐component reaction (Ugi 4CR) is an efficient tool which benefits from high atom efficiency, compatibility with green solvents such as methanol, simple purification, and a water side‐product. By using two bifunctional starting materials for Ugi 4CR, N‐substituted polyamides can be prepared via a step‐growth process. As polyamides play important roles in applications including films, and adhesives, the preparation of N‐substituted functional polyamides from largely sustainable monomers is investigated. Herein, the combination of renewable diamine, diacid, and aldehydes with commercially available isocyanides yield polyamides with tuneable side chain functionalities and ≈80% biomass content. Relatively high yields (up to 96%) are recorded for polymers of moderate molecular weights (Mw up to 8100 g mol−1). The prepared polyamides possess backbones which exhibit excellent thermal stability (Tdeg = 440 ± 10 °C), while functional side chains result in additional lower‐temperature degradations (215–285 °C). Side‐group variation enables shifting of the glass transition temperature (Tg) between 9 and 38 °C and causes variation in hydrophobicity resulting in water contact angles ranging from 47 o to 105 o. This work presents a reliable approach to prepare sustainable polymers with diverse side chain functionalities in a short reaction time and without need for catalysts or complicated purifications.

Periodically Functionalized Sequence‐Regulated Vinyl Polymers via Iterative Atom Transfer Radical Additions and Acyclic Diene Metathesis Polymerization

AbstractSequence‐regulated vinyl polymers with functional groups, such as aliphatic, aromatic, hydroxy, amino, and carboxylic acid groups, as found in natural macromolecules such as proteins, are one of the ultimate targets in synthetic polymers. This study is directed toward the synthesis of periodically functionalized sequence‐regulated vinyl polymers using a series of reactions consisting of iterative atom transfer radical additions (ATRAs) of vinyl monomers, allylation, functionalization, protection, acyclic diene metathesis (ADMET) polymerization, hydrogenation, and deprotection. The functionalized sequence‐regulated telechelic diene oligomers, possessing protected hydroxy, carboxylic acid, and amino groups in the pendant of the acrylate unit between two styrene units, are prepared by iterative ATRAs of two styrene molecules to methyl dichloroacetate followed by allylation of both C–Cl termini and substitution of methyl ester with the protected functionalized groups. The protected functionalized sequence‐regulated telechelic diene oligomers are then polymerized by ADMET polymerization to afford polymers with main‐chain internal olefins and protected functionalized side chains in the acryl units between the two styrene units. The subsequent hydrogenation and deprotection reactions produce a series of sequence‐regulated vinyl polymers with periodic polar functional groups such as –OH, –CO2H, and –NH3+Cl–. These functional groups affect the thermal properties and solubility of the polymers.

N-Amino-imidazol-2-one (Nai) Residues as Tools for Peptide Mimicry: Synthesis, Conformational Analysis and Biomedical Applications

Abstract N-Amino-imidazol-2-one (Nai) residues are tools for studying peptide-backbone and side-chain conformation and function. Recent methods for substituted Nai residue synthesis, conformational analysis by X-ray crystallography and computation, and biomedical applications are reviewed, demonstrating the utility of this constrained residue to favor biologically active turn conformers with defined χ-dihedral angle orientations.1 Introduction2 Synthetic Methods3 Conformational Analysis4 Biomedical Applications5 Conclusions

Effect of the Side Chain Functionality of the Conjugated Polyelectrolytes as a Cathode Interlayer Material on the Photovoltaic Performances

Effect of the Side Chain Functionality of the Conjugated Polyelectrolytes as a Cathode Interlayer Material on the Photovoltaic Performances

Solid-phase synthesis of novel antimicrobial peptoids with α- and β-chiral side chains.

Bacterial resistance to conventional antibiotics poses an immense threat to human health and consequently many bacterial infections arise from multi-drug resistant pathogens. It is, therefore, necessary to continue to develop novel antimicrobials. Peptoids are a novel class of antimicrobial agents that mimic the structures of peptides. These N-substituted glycines differ from peptides in the side chain attachment site where in peptoids, the side chain functionality is introduced at the nitrogen rather than the α-carbon in peptides. During the process of design and development of antimicrobial peptoids, several key elements such as charge and amphiphilicity appear to guide peptoid bioactivity against bacterial pathogens. In this study, we report a quick synthesis of three novel cationic antimicrobial peptoids that contain charged, hydrophobic, and chiral monomers. This study is the first to use a monomer that contains both charge and chiral center for the design of the novel peptoid sequences.

Spherical α-helical polypeptide-mediated E2F1 silencing against myocardial ischemia-reperfusion injury (MIRI).

Apoptosis of cardiomyocytes is a critical outcome of myocardial ischemia-reperfusion injury (MIRI), which leads to the permanent impairment of cardiac function. Upregulated E2F1 is implicated in inducing cardiomyocyte apoptosis, and thus intervention of the E2F1 signaling pathway via RNA interference may hold promising potential for rescuing the myocardium from MIRI. To aid efficient E2F1 siRNA (siE2F1) delivery into cardiomyocytes that are normally hard to transfect, a spherical, α-helical polypeptide (SPP) with potent membrane activity was developed via dendrimer-initiated ring-opening polymerization of N-carboxyanhydride followed by side-chain functionalization with guanidines. Due to its multivalent structure, SPP outperformed its linear counterpart (LPP) to feature potent siRNA binding affinity and membrane activity. Thus, SPP effectively delivered siE2F1 into cardiomyocytes and suppressed E2F1 expression both in vitro and in vivo after intramyocardial injection. The E2F1-miR421-Pink1 signaling pathway was disrupted, thereby leading to the reduction of MIRI-induced mitochondrial damage, apoptosis, and inflammation of cardiomyocytes and ultimately recovering the systolic function of the myocardium. This study provides an example of membrane-penetrating nucleic acid delivery materials, and it also provides a promising approach for the genetic manipulation of cardiomyocyte apoptosis for the treatment of MIRI.

Conjugated polymers for biomedical applications.

Conjugated polymers (CPs) are a series of organic semiconductor materials with large π-conjugated backbones and delocalized electronic structures. Due to their specific photophysical properties and photoelectric effects, plenty of CPs with varied chemical structures and functions are quickly evolving in the diverse biomedical field, such as fluorescence imaging, photodynamic therapy, photothermal therapy, etc. In addition, the functionalized side chains of CPs could contribute to the expected water-solubility, biocompatibility, biological response, etc. CPs can also be prepared into nanoparticles for acquiring controllable particle size and dispersion through the common synthesis procedure. In this review, we focus on the latest developments of CPs in biotherapy, biological regulation, biological response and bioprinting applications. The major challenges and outlooks of CPs for applications in the biomedical field are also discussed.

Biosynthetic incorporation for visualizing bacterial glycans.

Cell-surface glycans are central to many biological processes, yet methods for their site-selective modification are limited. Strategies for interrogating the structure and function of proteins have been enabled by chemoselective reactions of sidechain functionality for covalent modification, capture, or imaging. However, unlike protein sidechains, glycan building blocks lack distinguishing reactivity. Moreover, glycans are not primary gene products, so encoding glycan variants through genetic manipulation is challenging. Reactive functional groups can be introduced into glycans through metabolic engineering, which involves the generation of modified nucleotide-sugar building blocks. Lipid-linked building blocks, which are also used in glycan biosynthesis, have the advantage that they can be delivered directly to glycosyltransferases to function as surrogate substrates. This process, termed "biosynthetic incorporation," takes advantage of the properties of bacterial glycosyltransferase: they are selective for the products they generate yet promiscuous in their donor preferences. We describe how this strategy can be implemented to label arabinofuranose-containing glycans on the surface of mycobacterial cells. We anticipate that this platform can be expanded to develop chemoselective labeling agents for other important bacterial monosaccharides.

The combined influence of polythiophene side chains and electrolyte anions on organic electrochemical transistors

AbstractPolythiophenes with differently functionalized side chains (alkyl, oligoethylene oxide, ester, hydroxy, and carboxylic acid) and varied counter ions of potassium salt electrolytes were investigated in organic electrochemical transistors (OECTs). In addition, mixed blends were investigated to evaluate any synergistic effects between functionalities. Depending on the functional moiety attached, a large shift to lower potentials of Vth, an increase in drain current, and an increase in transconductance can be observed compared to the base combination of alkyl side chain and Cl−. The newly designed and synthesized hydroxy polymer displayed stability to large shifts in VTH, a slight increase in drain current, and little or no increase in transconductance when an ionic radius of the dopant is increased until a much larger anion, large polarizability, and low hydration number such as TSFI− was used. The acid‐functionalized polymer, on the other hand, had the same magnitude in shift with respect to any anion that is larger than Cl−. The polymers were characterized by spectroscopy, X‐ray diffraction, thermal analysis, and cyclic voltammetry. This work demonstrates that side‐chain engineering can result in substantial differences in the level of interaction in the electrolyte that would require tailoring the ion for specific polymer interactions.