Search Results (42)

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW < 1300 Da) containing amide functionality between 2021 and 2025, highlighting its continued and evolving role in addressing contemporary medical challenges. An analysis of these novel therapeutics reveals the remarkable functional versatility of the amide bond. In antiviral agents like nirmatrelvir (Paxlovid^®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati^®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide’s unique combination of planarity, resonance stabilization, and capacity for robust hydrogen bonding continues to make it an essential element in the medicinal chemist’s toolkit, underpinning the development of next-generation therapeutics across oncology, infectious diseases, and neurology. To provide a practical framework for drug discovery, the synthetic routes for each drug are detailed, with particular emphasis placed on the key amide-forming strategies employed. Full article

Pour point depressants (PPDs) based on functionalized polyolefins were obtained and evaluated for their efficiency in pour point reducing of Kumkol waxy crude oil (Kazakhstan), which contains 15.2 wt.% paraffin and has a pour point of +17 °C. An ethylene–propylene copolymer (EPR-505A) was treated through grafting of maleic anhydride (MA-g-PO) and then converted into three different derivatives that had an identical polymer backbone: an ester-functionalized, an amide-functionalized, and a combined ester–amide additive. The obtained products were tested at 500 g/t through kinematic viscosity measurements, equilibrium and kinetic interfacial tension analysis, pour point determination, cooling curve analysis, and optical microscopy. The ester derivative reduced the pour point by 7 °C, the amide derivative did so by 5 °C, and the combined additive achieved a 10 °C pour point reduction and a more than twofold decrease in kinematic viscosity at 0 °C. Interfacial tension measurements and adsorption kinetics allowed us to assume that ester groups govern macromolecular solubility and diffusion mobility, while amide groups enhance adsorption affinity at paraffin crystal surfaces. Their combined action shifts crystallization from a collective to a dispersed regime. These findings establish structure–activity relationships between polar group architecture and PPD efficiency. Full article

The creation of new potential metal-based therapeutics largely relies on the development of useful ligand scaffolds. In recent years, our research group has introduced thiophosphoryl-functionalized carboxamides as a convenient framework for obtaining biologically active cyclopalladated derivatives. In continuation of these studies, β-(aminoalkyl)phosphine sulfides bearing additional substituents in the ethylene backbone were synthesized for the first time and reacted with picolinic acid to afford a series of new functionalized amide ligands. The latter readily underwent direct cyclopalladation under the action of PdCl₂(NCPh)₂ under mild reaction conditions. The resulting S,N,N-complexes were studied for in vitro cytotoxicity against several solid and hematopoietic cancer cell lines, as well apoptosis induction and DNA damage ability, which showed their promising anticancer properties. In addition, moderate antibacterial activity was observed for a representative palladocycle of the β-thiophosphorylated derivatives. Full article

Polyamide 6 (PA6) is limited in its application in precision and high-temperature fields due to its high moisture absorption, low heat resistance, and poor barrier properties. To overcome these intrinsic deficiencies, a rigid 9-(carboxyphenyl)carbazole-based diacid monomer (CzIPA) was incorporated into the PA6 backbone via one-step melt polycondensation. Structural analyses confirmed successful copolymer formation and effective modulation of hydrogen-bonding interactions and chain rigidity. The introduction of the bulky carbazole units markedly enhanced the thermal and physical properties of PA6. The glass transition temperature increased by up to 35.5 °C, while the maximum decomposition temperature rose by 23.8 °C, reflecting the reduced chain mobility and strengthened thermal resistance. The decreased amide-group density led to a 15% reduction in water absorption, improving dimensional stability. The Young’s modulus, flexural strength, and flexural modulus of the prepared copolymers were significantly improved compared to PA6, while the toughness was slightly reduced. Furthermore, oxygen and water-vapor permeabilities were simultaneously reduced by 30–35%, attributed to restricted diffusion pathways in the modified microstructure. Despite the increased rigidity, the copolymers maintained good melt processability with clear shear-thinning behavior. This study demonstrates CzIPA copolymerization as an efficient structural design strategy for producing high-performance PA6 materials with enhanced thermal stability, lower hygroscopicity, and superior barrier properties. Full article

Background: Oral insulin improves compliance and convenience in patients with diabetes who require regular needle injections. However, the clinical application of oral insulin preparations has been limited due to instability and inefficient permeation through the gastrointestinal tract. In this study, a novel cationic polysaccharide nanodrug delivery platform was designed for efficient oral insulin delivery. Methods: The innovative thiolated trimethyl chitosan-grafted β-cyclodextrin (NCT) was synthesized by utilizing N-trimethyl chitosan (TMC) as the polymer backbone. This involved modifying TMC with thiol group-containing N-acetylcysteine and carboxymethyl-β-cyclodextrin that possesses hydrophobic cavities via an amide condensation reaction. Subsequently, this polymer was employed to construct the NCT nanoparticle system using an ionic cross-linking method. The physicochemical properties of the NCT nanoparticles were systematically analyzed, and their therapeutic efficacy was comprehensively evaluated in streptozotocin (STZ)-induced animal models. Results: The NCT nanoparticles demonstrated mucus adhesion, permeability, and pH sensitivity, which facilitated a slow and controlled release within the gastrointestinal microenvironment due to both ionic electrostatic interactions and disulfide bonding interactions. The experiments revealed in vivo that insulin/NCT nanoparticles extended the retention time of insulin in the small intestine. Blood glucose levels decreased to approximately 39% of the initial level at 5 h post-administration while exhibiting smooth hypoglycemic efficacy. Simultaneously, insulin bioavailability increased to 12.58%. Conclusions: The NCT nanoparticles effectively protect insulin from degradation in the gastrointestinal microenvironment while overcoming intestinal barriers, thereby providing a promising approach to oral biomolecule delivery. Full article

The lipooligosaccharide (LOS) of the marine bacterium Kangiella japonica KMM 3897 was structurally characterized using chemical analysis, NMR spectroscopy, and MALDI-TOF mass spectrometry. The oligosaccharide core consists of a monophosphorylated trisaccharide containing 2-amino-2-deoxy-D-glucose, D-glycero-D-manno-heptose, and 3-deoxy-D-manno-oct-2-ulosonic acid. The penta-acylated lipid A moiety features a glucosamine disaccharide backbone with phosphate groups and amide- and ester-linked primary fatty acids [i11:0 (3-OH)], along with a secondary acyl chain (i11:0 or 11:0). Immunostimulatory assays revealed that K. japonica KMM 3897 LOS induced significantly weaker cytokine production in human peripheral blood mononuclear cells (PBMCs) compared with E. coli LPS. Notably, it exhibited potent antagonistic activity against E. coli LPS-mediated toxicity and suppressed caspase-4 activation in LPS-treated PBMCs. These findings highlight its anti-inflammatory and protective properties. Full article

Methionine residues in proteins and peptides are frequently oxidized by losing one electron. The presence of nearby amide groups is crucial for this process, enabling methionine to participate in long-range electron transfer. Hydroxyl radical (HO^•) plays an important role being generated in aerobic organisms by cellular metabolisms as well as by exogenous sources such as ionizing radiations. The reaction of HO^• with methionine mainly affords the one-electron oxidation of the thioether moiety through two consecutive steps (HO^• addition to the sulfur followed by HO⁻ elimination). We recently investigated the reaction of HO^• with model peptides mimicking methionine and its cysteine-methylated counterpart, i.e., CH₃C(O)NHCHXC(O)NHCH₃, where X = CH₂CH₂SCH₃ or CH₂SCH₃ at pH 7. The reaction mechanism varied depending on the distance between the sulfur atom and the peptide backbone, but, for a better understanding of various suggested equilibria, the analysis of the flux of protons is required. We extended the previous study to the present work at pH 4 using pulse radiolysis techniques with conductivity and optical detection of transient species, as well as analysis of final products by LC-MS and high-resolution MS/MS following γ-radiolysis. Comparing all the data provided a better understanding of how the presence of nearby amide groups influences the one-electron oxidation mechanism. Full article

Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro skin equivalents and engineered grafts, the intrinsic limitations of native fibrin hydrogels in terms of long-term mechanical stability and resistance to degradation need to be addressed to enhance the usefulness and application of these hydrogels in tissue engineering. In this study, we chemically modified plasma-derived fibrin by incorporating succinimidyl alginate (SA), a version of alginate chemically modified to introduce reactive succinimidyl groups. These NHS ester groups (N-hydroxysuccinimide esters), attached to the alginate backbone, are highly reactive toward the primary amine groups present in plasma proteins such as fibrinogen. When mixed with plasma, the NHS groups covalently bond to the amine groups in fibrin, forming stable amide linkages that reinforce the fibrin network during hydrogel formation. This chemical modification improved mechanical properties, reduces contraction, and enhanced the stability of the resulting hydrogels. Hydrogels were prepared with a final fibrinogen concentration of 1.2 mg/mL and SA concentrations of 0.5, 1, 2, and 3 mg/mL. The objective was to evaluate whether this modification could create a more stable matrix suitable for supporting skin tissue development. The mechanical and microstructure properties of these new hydrogels were evaluated, as were their biocompatibility and potential to create 3D skin models in vitro. Dermo-epidermal skin cultures with primary human fibroblast and keratinocyte cells on these matrices showed improved dermal stability and better tissue structure, particularly SA concentrations of 0.5 and 1 mg/mL, as confirmed by H&E (Hematoxylin and Eosin) staining and immunostaining assays. Overall, these results suggest that SA-functionalized fibrin hydrogels are promising candidates for creating more stable in vitro skin models and engineered skin grafts, as well as for other types of engineered tissues, potentially. Full article

The safety concerns associated with sensitivity issues regarding long nitrogen chain-based energetic compounds, especially for eight or more catenated nitrogen atoms in backbones, need to be resolved. Incorporating specific functional groups represents a key approach for enhancing stability in organic energetic materials. This study reports the synthesis of 1,1′-(diazene-1,2-diyl)bis(4-nitro-1H-1,2,3-triazole-5-carboxamide) (S8), an N8-chain compound featuring strategically placed amide groups. Employing THA(O-tosylhydroxylamine) and KMnO₄, 1,1′-(diazene-1,2-diyl)bis(4-nitro-1H-1,2,3-triazole-5-carboxamide) (S8) was synthesized and underwent N-amination and oxidative azo coupling. Comprehensive characterization, including X-ray diffraction, mechanical sensitivity testing, and theoretical analysis, alongside comparative studies with known N8 compounds, revealed that S8 exhibits unprecedented stability within its class. Among reported N8-catenated nitrogen chain compounds, attributed to the incorporation of the amide functionality, S8 demonstrates the highest impact sensitivity (IS = 10 J) and friction sensitivity (FS = 40 N) while maintaining excellent detonation performance (D = 8317 ms⁻¹, P = 28.27 GPa). This work highlights the amide group as a critical structural part for achieving high stability in sensitive long-nitrogen-chain energetic materials without compromising performance. Full article

Peptoids are peptidomimetics in which the side chain is attached to the nitrogen of the amide group rather than the α-carbon. This alteration in the backbone structure is highly valued because it endows beneficial properties, including enhanced resistance to proteolysis, greater immunogenicity, improved biostability, and superior bioavailability. In this current study, we focused on the Ugi-4CR-based one-pot synthesis of peptoids using 1,4-dithiane-2,5-diol as the carbonyl component together with amine, carboxylic acid, and isocyanides. Four new peptoids—5a, 5b, 5c, and 5d—were designed and efficiently prepared in good chemical yields and were subjected to DFT investigations for their electronic behavior. These compounds have free OH, SH, and terminal triple bonds for further chemistry. In a computational analysis, the spectral data of compounds 5a–5d were juxtaposed with calculated spectral values derived from the B3LYP/6-311G(d,p) level. The electronic excitation and orbital contributions of 5a–5d were predicted using TD-DFT calculations. A natural bond order (NBO) analysis was utilized to investigate the electronic transition of newly synthesized peptoids, focusing on their charge distribution patterns. Furthermore, MEP and NPA analyses were conducted to predict charge distribution in these compounds. The reactivity and stability of the targeted peptoids were evaluated by global reactivity descriptors, which were determined with frontier molecular orbital analysis. The DFT results revealed that compound 5c displayed marginally higher reactivity compared to 5a, 5b, and 5d, possibly due to its extended conjugation. Full article

The formation of self-crosslinking chitosan hydrogels using carboxylic acids has a number of limitations. Chitosan dissolves in oxalic, malonic, and succinic acids at a ratio of 1 amino group to 2 carboxyl groups into viscous solutions (G′ < G′′), but does not dissolve with lower amounts of the acid. Mixing chitosan hydrochloride with disodium carboxylates does not afford gels, but only a coacervate in the case of disodium oxalate, which dissolves upon dialysis. In the homologous series of N-carboxyalkyl derivatives (alkyl = methyl, ethyl, propyl), all members form gels (G′ > G′′). At approx. 50% of substitution, the storage modulus increases from 40 Pa (methyl) to 30,000 Pa (propyl) indicating the increasing strength of intermolecular interactions with the increasing length of the alkyl spacer. This could indicate that a sufficiently long spacer is required to properly connect the chitosan helices. N-succinyl chitosan, where the spacer is attached to the backbone as an amide, also forms polymer gels across all degrees of N-acylation. When compared to N-carboxypropyl chitosan, the latter forms significantly stiffer gels that swell less. This indicates that one covalent bond, a sufficient length, and the conformational flexibility of the spacer are important for gelation. Full article

Polybenzimidazole (PBI) is a high-performance polymer known for its excellent thermal stability, mechanical strength, and chemical resistance, attributes that are derived from its unique structure comprising repeated benzene and imidazole rings. However, limitations such as relatively low thermal stability and moisture sensitivity restrict its application as a super engineering plastic. In this study, amide groups are incorporated into the PBI backbone to synthesize the copolymer poly(BI-co-A), effecting a structural modification at the molecular level. Additionally, silica nanospheres were composited into the poly(BI-co-A) film to further enhance its thermal performance. The resulting composite films exhibited remarkable thermal stability, with the temperature for 10% weight loss reaching as high as 761 °C. To address increased water absorption due to the high hydrophilicity of hydroxyl groups on the silica nanospheres’ surface, a dehydration treatment was applied in an electric furnace. This treatment produced a highly thermoresistant poly(BI-co-A) nanocomposite film with reduced wettability, making it suitable for applications in humid environments. Full article

Glycopolymers are functional polymers with saccharide moieties on their side chains and are attractive candidates for biomaterials. Postpolymerization modification can be employed for the synthesis of glycopolymers. Activated esters are useful in various fields, including polymer chemistry and biochemistry, because of their high reactivity and ease of reaction. In particular, the formation of amide bonds caused by the reaction of activated esters with amino groups is of high synthetic chemical value owing to its high selectivity. It has been employed in the synthesis of various functional polymers, including glycopolymers. This paper reviews the recent advances in polymers bearing activated esters for the synthesis of glycopolymers by postpolymerization modification. The development of polymers bearing hydrophobic and hydrophilic activated esters is described. Although water-soluble activated esters are generally unstable and hydrolyzed in water, novel polymer backbones bearing water-soluble activated esters are stable and useful for postpolymerization modification for synthesizing glycopolymers in water. Dual postpolymerization modification can be employed to modify polymer side chains using two different molecules. Thiolactone and glycine propargyl esters on the polymer backbone are described as activated esters for dual postpolymerization modification. Full article

Fully room temperature three-dimensional (3D) shape-reprogrammable, recyclable, and photomobile azobenzene (azo) polymer actuators hold much promise in many photoactuating applications, but their development is challenging. Herein, we report on the efficient synthesis of a series of main-chain azo liquid crystalline polymers (LCPs) with such performances via Michael addition polymerization. They have both ester groups and two kinds of hydrogen bond-forming groups (i.e., amide and secondary amino groups) and different flexible spacer length in the backbones. Such poly(ester-amide-secondary amine)s (PEAsAs) show low glass transition temperatures (T_g ≤ 18.4 °C), highly ordered smectic liquid crystalline phases, and reversible photoresponsivity. Their uniaxially oriented fibers fabricated via the melt spinning method exhibit good mechanical strength and photoinduced reversible bending/unbending and large stress at room temperature, which are largely influenced by the flexible spacer length of the polymers. Importantly, all these fibers can be easily reprogrammed under strain at 25 °C into stable fiber springs capable of showing a totally different photomobile mode (i.e., unwinding/winding), mainly owing to the presence of low T_g and both dynamic hydrogen bonding and stable crystalline domains (induced by the uniaxial drawing during the fiber formation). They can also be recycled from a solution at 25 °C. This work not only presents the first azo LCPs with 3D shape reprogrammability, recyclability, and photomobility at room temperature, but also provides some important knowledge of their structure–property relationship, which is useful for designing more advanced photodeformable azo polymers. Full article

The idea of flexible body armor has been around for many years. Initial development included shear thickening fluid (STF) as a backbone polymer to impregnate ballistic fibers such as Kevlar. At the core of the ballistic and spike resistance was the instantaneous rise in viscosity of STF during impact. Increase in viscosity was due to the hydroclustering of silica nanoparticles dispersed in polyethylene glycol (PEG) through a centrifuge and evaporation process. When STF composite was dry, hydroclustering was not possible due to absence of any fluidity in PEG. However, particles embedded within the polymer, covered the Kevlar fiber and offered some resistance to spike and ballistic penetration. The resistance was meagre and hence, the goal was to improve it further. This was achieved by creating chemical bonds between particles, and by strongly attaching particles to the fiber. PEG was replaced with silane (3-amino propyl trimethoxysilane), and a fixative cross-linker, Glutaraldehyde (Gluta), was added. Silane installed an amine functional group on the silica nanoparticle surface, and Gluta created strong bridges between distant pairs of amine groups. Amide functional groups present in Kevlar also interacted with Gluta and silane to form a secondary amine, allowing silica particles to attach to fiber. A network of amine bonding was also established across the particle-polymer-fiber system. In synthesizing the armor, silica nanoparticles were dispersed in a mixture of silane, ethanol, water, and Gluta, maintaining an appropriate ratio by weight, and using a sonication technique. Ethanol was used as a dispersion fluid and was evaporated later. Several layers of Kevlar fabric were then soaked with the admixture for about 24 h and dried in an oven. Armor composites were tested in a drop tower according to NIJ115 Standard using spikes. Kinetic energy at impact was calculated and normalized with the aerial density of the armor. NIJ tests revealed that normalized energy for 0-layer penetration increased from 10 J-cm²/g (STF composite) to 220 J-cm²/g for the new armor composite, indicating a 22-fold enhancement. SEM and FTIR studies confirmed that this high resistance to spike penetration was due to the formation of stronger C-N, C-H, and C=C-H stretches facilitated by the presence of silane and Gluta. Full article