Variety Of Side Chains Research Articles

Ultrafast Spectroscopic Studies on Excited State Dynamics of Different Alkyl Substituted Perylene Monoimides in Solution and Thin Films

AbstractPerylene monoimides (PMI) are a unique class of polyaromatic molecules, which are known to undergo interesting excited state processes, making them attractive for the applications in optoelectronic devices. In this paper a comprehensive investigation is conducted on the photophysical properties and excited state dynamics of a series of PMI derivatives (PMI‐C18, PMI‐CE6, PMI‐C8, and PMI‐C6), with varying side chains substituted at the imide position. These studies involved utilization of both steady state and time resolved spectroscopic techniques. Femtosecond transient absorption (TA) spectroscopic studies demonstrated that PMI derivatives exhibit similar fluorescence characteristic in solution, irrespective of the various side chains substituted at the imide position. However, in thin films the various side chains led to prominent differences in their packing arrangement, which leads to difference in the TA spectra as compared to solution. The difference in the packing arrangement in PMI thin films is studied using X‐ray diffraction (XRD) spectroscopy. It is notable that the PMI‐CE6 thin films exhibited the existence of triplet state. The distinctive behavior of PMI‐CE6 is attributed to the distinct packing arrangement, providing role of molecular structure in influencing the excited state dynamics. The triplet state formation in PMI thin films renders them well‐suited for utilization in optoelectronic devices.

Impact of Side Chains in 1-n-Alkylimidazolium Ionomers on Cu-Catalyzed Electrochemical CO2 Reduction.

This study presents the impact of the side chains in 1-n-alkylimidazolium ionomers with varying side chain lengths (CnH2n+1 where n = 1, 4, 10, 16) on Cu-catalyzed electrochemical CO2 reduction reaction (CO2RR). Longer side chains suppress the H2 and CH4 formation, with the n-hexadecyl ionomer (n = 16) showing the greatest reduction in kinetics by up to 56.5% and 60.0%, respectively. On the other hand, C2H4 production demonstrates optimal Faradaic efficiency with the n-decyl ionomer (n = 10), a substantial increase of 59.9% compared to its methyl analog (n = 1). Through a combination of density functional theory calculations and material characterization, it is revealed that the engineering of the side chains effectively modulates the thermodynamic stability of key intermediates, thus influencing the selectivity of both CO2RR and hydrogen evolution reaction. Moreover, ionomer engineering enables industrially relevant partial current density of -209.5 mA cm-2 and a Faradaic efficiency of 52.4% for C2H4 production at 3.95 V, even with a moderately active Cu catalyst, outperforming previous benchmarks and allowing for further improvement through catalyst engineering. This study underscores the critical role of ionomers in CO2RR, providing insights into their optimal design for sustainable chemicalsynthesis.

Divergent Syntheses of Near-Infrared Light-Activated Molecular Jackhammers for Cancer Cell Eradication.

Aminocyanines incorporating Cy7 and Cy7.5 moieties function as molecular jackhammers (MJH) through vibronic-driven action (VDA). This mechanism, which couples molecular vibrational and electronic modes, results in picosecond-scale concerted stretching of the entire molecule. When cell-associated and activated by near-infrared light, MJH mechanically disrupts cell membranes, causing rapid necrotic cell death. Unlike photodynamic and photothermal therapies, the ultrafast vibrational action of MJH is unhindered by high concentrations of reactive oxygen species scavengers and induces only a minimal temperature increase. Here, the efficient synthesis of a library of MJH is described using a practical approach to access a key intermediate and facilitating the preparation of various Cy7 and Cy7.5 MJH with diverse side chains in moderate to high yields. Photophysical characterization reveals that structural modifications significantly affect molar extinction coefficients and quantum yields while maintaining desirable absorption and emission wavelengths. The most promising compounds, featuring dimethylaminoethyl and dimethylcarbamoyl substitutions, demonstrate up to sevenfold improvement in phototherapeutic index compared to Cy7.5 amine across multiple cancer cell lines. This synthetic strategy provides a valuable platform for developing potent, light-activated therapeutic agents for cancer treatment, with potentially broad applicability across various cancer types.

Synthesis and In Vivo Profiling of Desymmetrized Antimalarial Trioxolanes with Diverse Carbamate Side Chains.

The recent withdrawal of artefenomel from clinical development leaves no endoperoxide-class agents in the antimalarial pipeline. Synthetic endoperoxides with a desymmetrized structure have demonstrated promising physiochemical and in vivo properties. Here we expand on our initial investigation of trans-3″ carbamate substitution with a diverse array of amine-, alcohol-, and sulfinyl-terminated analogues prepared in (S,S) and (R,R) configurations. In general, this chemotype combines low-nM antiplasmodial activity with excellent aqueous solubility but widely varying human liver microsome (HLM) stability. We evaluated 20 novel analogues in the P. berghei mouse malaria model, identifying new analogues such as RLA-4767 (9a) and RLA-5489 (9d), with HLM stability and pharmacokinetic profiles superior to analogues from our initial report (e.g., RLA-4776, 8a). These new leads approach or equal the efficacy of artefenomel after two daily oral doses of 10 mg/kg, thus revealing a promising chemotype with the potential to deliver development candidates.

Modular Design and Self-assembly of pH-Responsive Multidomain Peptides Incorporating Non-natural Ionic Amino Acids.

Stimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non-natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH-responsive properties and enabling rational design based on desired transitional pH ranges. The structure-activity relationship of these pH-responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications.

Synthesis and Performance of Bithiophene Isoindigo Organic Semiconductors with Side‐Chain Functionality in Transistors

AbstractThe isoindigo and its derivatives have rapidly garnered attention as widely employed electron‐deficient moieties, finding extensive applications in organic field‐effect transistors. In this study, four different isoindigo‐based organic semiconductor polymers were synthesized via a Stille coupling reaction of four isoindigo molecules with varying side chains serving as acceptors and bithiophene as donors. Furthermore, their optical, electrochemical, thermal stability, and other relevant properties were comprehensively evaluated. These polymers exhibited remarkable electrochemical and thermal stability attributed to their low LUMO energy level, which facilitates effective electrical contact between the semiconductor layer and the source/drain while ensuring excellent air stability for the semiconductor polymers. Additionally, solution‐gate field‐effect transistors prepared using these polymers achieved hole mobilities of 10−2 cm2 V−1 S−1 along with an Ion/Ioff ratio of 8.39×103, demonstrating exceptional field‐effect performance.

Exploration of Tertiary Structure in Sequence-Defined Polymers Using Molecular Dynamics Simulations.

Peptoids are a class of sequence-defined biomimetic polymers with peptide-like backbones and side chains located on backbone nitrogens rather than alpha carbons. These materials demonstrate a strong ability for precise control of single-chain structure, multiunit self-assembly, and macromolecular assembly through careful tuning of sequence due to the diversity of available side chains, although the driving forces behind these assemblies are often not understood. Prior experimental work has shown that linked 15mer peptoids can mimic the protein helical hairpin structure by leveraging the chirality-inducing nature of bulky side chains and hydrophobicity, but there are still gaps in our understanding of the relationship between sequence, stability, and particular secondary or tertiary structure. We present a molecular dynamics (MD) study on the folding behavior of these polymers into hairpins, discussing the differences in structure from sequences with various characteristics in water and acetonitrile, and then compare the handedness preference of common helical motifs between solvents.

Temperature-dependent physicochemical studies of sodium salicylate in aqueous solutions of ionic liquids {[BMIm]Br and [EMIm]Cl}

The current study explores the impact of two different imidazolium based ionic liquids, having diverse side chains and anions: 1-ethyl-3-methylimidazolium chloride ([EMIm]Cl) and 1‑butyl‑3-methylimidazolium bromide ([BMIm]Br) on the thermodynamic and transport properties of sodium salicylate. This inquiry examines the sodium salicylate's density, sound velocity, and viscosity within aqueous solutions of these ionic liquids across a temperature range of 283.15 K to 313.15 K at atmospheric pressure. Various parameters, including apparent molar volume (Vϕ), limiting apparent molar volume (Voϕ), transfer volume (ΔtrV∘ϕ), limiting apparent molar expansibility (E∘∅), Hepler's constant, apparent molar isentropic compression (Kϕ,s), limiting apparent molar isentropic compression (K∘ϕ,s), transfer parameter of isentropic compression (ΔtrK∘ϕ,S), and viscosity B-coefficient, were computed from experimental values. Additionally, we have analyzed the trends in computed parameters, considering the interactions between `solute and solvent along with solute-solute interactions in the systems under investigation. Our results suggest a predominance of hydrophilic-hydrophilic and ion-hydrophilic interactions within studied systems. The observed magnitudes of these parameters affirm a stronger interaction between sodium salicylate and [BMIm]Br in comparison to those with [EMIm]Cl.

Relationships of Prodiginins Mechanisms and Molecular Structures to their Antiproliferative Effects.

The Prodiginins (PGs) natural pigments are secondary metabolites produced by a broad spectrum of gram-negative and gram-positive bacteria, notably by species within the Serratia and Streptomyces genera. These compounds exhibit diverse and potent biological activities, including anticancer, immunosuppressive, antimicrobial, antimalarial, and antiviral effects. Structurally, PGs share a common tripyrrolic core but possess variable side chains and undergo cyclization, resulting in structural diversity. Studies have investigated their antiproliferative effects on various cancer cell lines, with some PGs advancing to clinical trials for cancer treatment. This review aims to illuminate the molecular mechanisms underlying PG-induced apoptosis in cancer cells and explore the structure-activity relationships pertinent to their anticancer properties. Such insights may serve as a foundation for further research in anticancer drug development, potentially leading to the creation of novel, targeted therapies based on PGs or their derivatives.

Ortho-quinone methide driven synthesis of kynurenic acid lactams.

Lactam formation of different KYNA amides and Mannich bases mediated by ortho-quinone methide has been investigated. The efficiency of the two routes of the cyclization process was revealed and the influence of diverse amide side chains was explored. In this regard compounds bearing a tertiary amine function in the amide side chain resulted in the formation of the lactam product, while the formation of dimer derivatives was observed in the case of other KYNA amides. Furthermore, derivatives bearing different substituents on the KYNA B ring were synthesized and their effects on the ring-closure reaction were investigated.

Design and synthesis of 7-membered lactam fused hydroxypyridinones as potent metal binding pharmacophores (MBPs) for inhibiting influenza virus PAN endonuclease

Since influenza virus RNA polymerase subunit PAN is a dinuclear Mn2+ dependent endonuclease, metal-binding pharmacophores (MBPs) with Mn2+ coordination has been elucidated as a promising strategy to develop PAN inhibitors for influenza treatment. However, few attentions have been paid to the relationship between the optimal arrangement of the donor atoms in MBPs and anti-influenza A virus (IAV) efficacy. Given that, the privileged hydroxypyridinones fusing a seven-membered lactam ring with diverse side chains, chiral centers or cyclic systems were designed and synthesized. A structure-activity relationship study resulted in a hit compound 16l (IC50 = 2.868 ± 0.063 μM against IAV polymerase), the seven-membered lactam ring of which was fused a pyrrolidine ring. Further optimization of the hydrophobic binding groups on 16l afforded a lead compound (R, S)-16s, which exhibited a 64-fold more potent inhibitory activity (IC50 = 0.045 ± 0.002 μM) toward IAV polymerase. Moreover, (R, S)-16s demonstrated a potent anti-IAV efficacy (EC50 = 0.134 ± 0.093 μM) and weak cytotoxicity (CC50 = 15.35 μM), indicating the high selectivity of (R, S)-16s. Although the lead compound (R, S)-16s exhibited a little weaker activity than baloxavir, these findings illustrated the utility of a metal coordination-based strategy in generating novel MBPs with potent anti-influenza activity.

Biosynthesis of Strained Amino Acids by a PLP‐Dependent Enzyme through Cryptic Halogenation

AbstractAmino acids (AAs) are modular building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non‐ribosomal peptides. While the 20 main proteinogenic AAs display relatively limited side chain diversity, a wide range of non‐canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis, but contain a broad array of structural features and functional groups. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C4 position of lysine by a radical halogenase, PazA. The cyclopropane ring is then formed in the next step by a pyridoxal‐5′‐phosphate‐dependent enzyme, PazB, via an SN2‐like attack at C4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine potentially inhibits ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane‐containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology.

Biosynthesis of Strained Amino Acids by a PLP-Dependent Enzyme through Cryptic Halogenation.

Amino acids (AAs) are modular building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides. While the 20 main proteinogenic AAs display relatively limited side chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis, but contain a broad array of structural features and functional groups. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C4 position of lysine by a radical halogenase, PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5'-phosphate-dependent enzyme, PazB, via an SN2-like attack at C4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine potentially inhibits ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology.

Structure elucidation and antioxidant activity of a polysaccharide from Penthorum chinense Pursh

Penthorum chinense Pursh is a traditional Miao medicine, mainly used in the treatment of liver diseases. In this study, an acidic heteropolysaccharide PCPP was isolated from P. chinense with an average molecular weight of 14.96 kDa. PCPP contained arabinogalactan and homogalacturonan segments, which is formed by 4-Galp-(1 → 5)-Araf-1 and 3,6-Galp-(1 → 6)-Galp-1,3 glycosidic linkage. A variety of side chains, including t-Glcp-(1 → 4)-Glcp-(1 → 4)-GlcpA-1, t-Xylp-(1→, and 2-Manp-(1 → 4)-GalpA-1,3 linked to the O-3 and O-6 of 3,6-Galp. The antioxidant activity measurement in three models demonstrated that PCPP exhibited ROS scavenging capacity, antioxidant ability in the cellular model, enhancement of oxidative stress resistance, and healthspan-promoting effect in the worm model. These results provided the theoretical fundament of PCPP as a potential natural antioxidant.

Hierarchical assembly of peptoids on MoS2

Bio-macromolecular assembly forms intricate scaffolds in living systems that allow them to biomineralize bone, enamel, and shell. Such bioinspired approaches have also been widely used in biohybrid materials synthesis. Recently, researchers have demonstrated functional bioelectronic structures by assembling biopolymers, including proteins and peptides, on van der Waals (VdW) materials for sensors and energy storage and harvesting. However, the hierarchical assembly of biopolymers on VdW materials has yet to be fully documented, because modulating the assembly architectures by controlling the energy landscape along with environmental stimuli, in which various assembly phases occur, remains challenging. In this study, we focused on peptoids, biomimetic polymers with properties similar to peptides but offering advantages such as greater side chain diversity, lower complexity due to elimination of backbone-backbone hydrogen binding, lower synthesis costs, and improved stability. Specifically, we designed two short peptoid sequences capable of assembling on MoS2. Our findings reveal diverse self-assembled phases, including monolayer hybrid films with high crystallinity, vesicle-like nanoparticles, lamellae, and multi-layer ribbons. We elucidated the assembly processes of these states and confirmed the occurrence of phase transitions between them by using in situ atomic force microscopy (AFM). The results highlight the critical roles of peptoid-peptoid, peptoid-solvent, and peptoid-MoS2 interactions. These insights significantly advance the understanding needed to design hierarchical biopolymer architectures at VdW material-solvent interfaces with potential implications for enhancing the performance of bioelectronic devices based on 2D vdW materials.

Effect of different side chains on alternating copolymers of benzodithiophene and thiophene in organic solar cells

AbstractPolymeric semiconductors offer the dual advantages of lightness and flexibility, facilitating the large‐scale production of organic electronic devices. In the present research, electron donor polymers were synthesized incorporating high electron density aromatic units, specifically benzodithiophene (BDT) and thiophene (Th), to explore their efficacy in organic electronics. This systematic study focused on evaluating the impact of varying side chains on the material properties of these polymers. It was found that polymers with Th side chains exhibited significantly enhanced thermal stability, approximately 100°C higher than their alkoxide side chain counterparts. For the polymer PEHO‐BDT3HT, a bandgap value of around 1.6 eV was obtained. Furthermore, binary devices were developed using these novel copolymers, among which PDT‐BDT3HT demonstrated superior photovoltaic performance, achieving a power conversion efficiency of 1.56% without any optimization. This work not only sheds light on the influence of side chain variations in polymer properties but also showcases the potential of BDT and Th‐based copolymers in the field of organic electronics.

Meticulous Molecular Engineering of Crystal Orientation and Morphology in Conjugated Polymer Thin Films for Field-Effect Transistors.

The ability to precisely tailor molecular packing and film morphology in conjugated polymers offers a robust means to control their optoelectronic properties. This, however, remains a grand challenge. Herein, we report the dependency of molecular packing of an important conjugated polymer, poly(2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT), on a set of intrinsic parameters and unveil the correlation between their crystalline structures and charge transport characteristics. Specifically, a family of PBTTT with varying side chains (i.e., hexyl, octyl, decyl, dodecyl, tetradecyl, and hexadecyl referred to as C6, C8, C10, C12, C14, and C16, respectively) and molecular weights (MWs) with a focus on C14 are judiciously designed and synthesized. Various crystalline structures are yielded by tuning the alkyl chain and MW of PBTTT together with thermal annealing. It reveals that extending the alkyl chain length of PBTTT to C14, along with a larger MW and heating at 180 °C, promotes the formation of edge-on crystallites with significantly improved orientation and ordering. Furthermore, these distinct crystalline structures greatly impact their charge mobilities. This study sheds light on the tailored design of crystalline structures in PBTTT through a synergetic approach, which paves the way for potential applications of PBTTT and other conjugated polymers in optoelectronic devices with enhanced performance.

Synthesis of asymmetric cationic zinc porphyrin photosensitizer containing thiophene group for photodynamic therapy in vitro and theoretical calculation of DFT

Porphyrins, as photosensitizers for photodynamic therapy, is used to treat various cancers. In this study, three different side-chain variants of thiophene-zinc porphyrins were synthesized (Zn-P1, Zn-P2, and Zn-P3). Among the synthesized compounds, Zn-P1 exhibited the highest activity and demonstrated superior singlet oxygen generation capability according to both density functional theory calculations and singlet oxygen generation experiments. Our cytotoxicity assays revealed that Zn-P1 exhibited remarkable phototoxicity along with a pronounced selectivity for HepG2 cells. This selectivity was confirmed by cell staining experiments, which showed obvious apoptotic processes. Further insight into this anticancer mechanism was provided by cell reactive oxygen species experiments, which explained the induction of cancer cell apoptosis. Light-activated production of reactive oxygen species by photosensitizers initiates the apoptotic cascade in cancer cells. This study highlights the utility of cationic porphyrin photosensitizer complexes in photodynamic therapy and provides new insights for the development of innovative photosensitizers in cancer treatment.

Azo-linked room temperature columnar liquid crystals with bisphenol A core: Structure property relationship and photophysical properties

A series of bent-shaped liquid crystals containing an azo group and a bisphenol A core were synthesized, and characterized using various techniques. The presence of mesogenic properties in these azo-based dimers was confirmed through POM, DSC, and high-temperature XRD analysis. The structure-property relationship is further studied to confirmed the effect of the variable alkyl side chain on the terminal position, which also affects the liquid crystalline properties of the compounds in terms of mesophase temperature range and thermal stability. All the compounds exhibited enantiotropy columnar hexagonal phase with wide temperature range and thermal stability. Their photophysical properties were investigated using UV–visible spectroscopy and spectrofluorometry. It was observed that all four columnar mesogens underwent cis and trans azo isomerization upon exposure to photoisomerization.

Enantioselective organocatalytic strategies to access noncanonical α-amino acids.

Organocatalytic asymmetric synthesis has evolved over the years and continues to attract the interest of many researchers worldwide. Enantiopure noncanonical amino acids (ncAAs) are valuable building blocks in organic synthesis, medicinal chemistry, and chemical biology. They are employed in the elaboration of peptides and proteins with enhanced activities and/or improved properties compared to their natural counterparts, as chiral catalysts, in chiral ligand design, and as chiral building blocks for asymmetric syntheses of complex molecules, including natural products. The linkage of ncAA synthesis and enantioselective organocatalysis, the subject of this perspective, tries to imitate the natural biosynthetic process. Herein, we present contemporary and earlier developments in the field of organocatalytic activation of simple feedstock materials, providing potential ncAAs with diverse side chains, unique three-dimensional structures, and a high degree of functionality. These asymmetric organocatalytic strategies, useful for forging a wide range of C-C, C-H, and C-N bonds and/or combinations thereof, vary from classical name reactions, such as Ugi, Strecker, and Mannich reactions, to the most advanced concepts such as deracemisation, transamination, and carbene N-H insertion. Concurrently, we present some interesting mechanistic studies/models, providing information on the chirality transfer process. Finally, this perspective highlights, through the diversity of the amino acids (AAs) not selected by nature for protein incorporation, the most generic modes of activation, induction, and reactivity commonly used, such as chiral enamine, hydrogen bonding, Brønsted acids/bases, and phase-transfer organocatalysis, reflecting their increasingly important role in organic and applied chemistry.