Intermolecular Research Articles

Anticancer activity of Co(III) complex containing mixed ligand bis(5-phenyl-1,2,4-triazole)-3-sulfinamide and o-phen: Crystal structure, DFT, and Hirshfeld Surface Analysis

The cobalt complexes have demonstrated potential as antibacterial, antifungal, and anticancer agents, further enhancing their significance in the field. Here, a cobalt (III) complexes [Co(ptsm)H2O(o-phen)]·CH3OH containing in situ formed bis(5-phenyl-1,2,4-triazole)-3-sulfinamide (ptsm), 1,10-phenanthroline, and H2O molecule as ligand along with methanol molecule as crystallised solvent has been synthesised and characterised by various spectroscopic and X-ray crystallography techniques. The cobalt complex crystallises in a triclinic system with space group P-1. The DFT and TD-DFT calculations were also performed to optimise geometry and better understand electronic transitions. The outcomes of quantum chemical calculations (TD-DFT and DFT) match the characteristics of the experiments. Various intermolecular interactions in complex 1 have been quantitively explained with Hirshfeld surface analysis. The M.T.T. assay assessed the cytotoxicity of complex 1 against Dalton's lymphoma (DL) cells, yielding IC50 values of 40 µM. The A.O./EtBr dual staining and D.A.P.I. staining further confirms the cytotoxic potential of the complex 1.

Dual responsive behaviors in fluorescence of molecular crystals based on naphthalene pyridyl derivatives

Three compounds based on naphthalene and pyridine structures with different nitrogen positions (NP-2, NP-3, and NP-4) were synthesized. Except for displaying aggregation-induced emission (AIE) properties, the solution and crystals of these compounds show reversible fluorescence changes under alternative acid and base treatments. Experimental results, including X-ray diffraction, optical spectroscopy measurements, and cross-polarized microscope characterization, suggested that compounds might undergo reversible crystal-to-crystal transition upon external acid and base stimuli. It also revealed that the position of the heteroatom nitrogen in the pyridine unit significantly affected the intra- and intermolecular interactions, leading to restricted-intermolecular motions (RIMs) that caused the AIE effect. Besides, computational calculations indicated significant changes in molecular geometries and electronic interactions between the initial states and the protonated states. An information encryption system involving activation and operation codes was established based on the multiple stimuli-responsive properties. Our work not only presents a facile way to develop multiple responsive properties in molecular crystal systems but also explores their potential as highly emissive functional dyes for future applications.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

Structural and computational exploration of zwitterionic and quinoidal forms in Schiff base compound

The stable NH-form of the Schiff base compound, (Z)-6-(((4-chlorobenzyl) amino) methylene)-2-hydroxycyclohexa-2,4-dienone was synthesized and characterized by FTIR, SEM, EDAX anlysis and X-ray crystallographic analysis. Structural analysis was carried out to examine the NH-form of the halogen-based Schiff base compound. Additionally, an analysis of bond lengths, based on previously reported NH-forms of other Schiff bases, was conducted to distinguish between the zwitterion and quinoid structures. Further, Hirshfeld surface analysis was performed to visualize and quantify intermolecular interactions, supported by shape index, 2D fingerprint plots, and Enrichment ratio analyses, highlighting the importance of these interactions. Energy frameworks were established to deepen the understanding of crystal packing through the computation of intermolecular interaction energies. QTAIM analysis was performed to visualize and quantify intramolecular interactions, while Density Functional Theory (DFT) studies elucidated molecular properties such as the HOMO-LUMO energy gap and its derivatives. Evaluation of antibacterial activity against S. aureus was conducted via the disc diffusion assay supplemented by molecular docking studies. This comprehensive approach provides valuable structural insights into the NH-form, as well as molecular and biological aspects of (Z)-6-(((4-chlorobenzyl) amino) methylene)-2-hydroxycyclohexa-2,4-dienone.

Enhancement of the gelling properties of Aristichthys nobilis: Insights into intermolecular interactions between okra polysaccharide and myofibrillar protein

The effects of various contents of okra polysaccharide (OP) (0%-1%) on myofibrillar protein (MP) gelation and the interaction mechanism between OP and MP were investigated. OP improved the gelling properties of MP with an additive limitation of 0.75%. Rheological analysis demonstrated that the addition of OP enhanced the interactions between MPs, resulting in a denser intermolecular gel network structure. The addition of OP shifted the I850/I830 of Fourier transform infrared spectroscopy, indicating that hydrogen bonds were formed between OP and MP. Adding OP promoted the transition from α-helix to β-sheet in the MP. OP exposed the hydrophobic groups of MPs and increased the number of hydrophobic interactions between them, favoring the formation of a dense gel network. Molecular docking predicted that hydrogen bonds were the main force involved in the binding of OP and MP. Moderate OP promoted the aggregation of MPs and improved their functional properties, facilitating heat-induced gelation.

Highly branched thermoresponsive polysaccharide derivative in water. Partly substituted highly branched cyclic dextrin ethylcarbamate

A thermoresponsive highly branched polysaccharide derivative was revealed from commercially available highly branched cyclic dextrin (HBCD), originally synthesized from amylopectin. Eight samples of partially substituted ethyl carbamate derivatives of HBCD (HEC) were prepared with a degree of substitution DS ranging from 0.27 to 1.46. Three samples with DS = 0.88, 1.05, and 1.22 showed LCST type phase separation in water. The intrinsic viscosity and form factor in water were typical of the hyperbranched structure. The intermolecular interactions between HEC and iodine or 1-anilinonaphthalene-8-sulfonic acid (ANS) were appreciably different from those of the linear analog (AEC), suggesting that the locally bent helical conformation of highly branched HEC chains has a different interaction with small molecules. The phase diagram of HEC-water systems was accidentally similar to that of the linear chain with the same molar mass and DS, although the one phase region of the branched polymer chain-poor solvent system is usually wider than that of the corresponding linear chain. This is likely due to the lower hydration nature of the polymer segment of HEC chains than that of the corresponding linear chain.

Highly branched thermoresponsive polysaccharide derivative in water. Partly substituted highly branched cyclic dextrin ethylcarbamate

A thermoresponsive highly branched polysaccharide derivative was revealed from commercially available highly branched cyclic dextrin (HBCD), originally synthesized from amylopectin. Eight samples of partially substituted ethyl carbamate derivatives of HBCD (HEC) were prepared with a degree of substitution DS ranging from 0.27 to 1.46. Three samples with DS = 0.88, 1.05, and 1.22 showed LCST type phase separation in water. The intrinsic viscosity and form factor in water were typical of the hyperbranched structure. The intermolecular interactions between HEC and iodine or 1-anilinonaphthalene-8-sulfonic acid (ANS) were appreciably different from those of the linear analog (AEC), suggesting that the locally bent helical conformation of highly branched HEC chains has a different interaction with small molecules. The phase diagram of HEC-water systems was accidentally similar to that of the linear chain with the same molar mass and DS, although the one phase region of the branched polymer chain-poor solvent system is usually wider than that of the corresponding linear chain. This is likely due to the lower hydration nature of the polymer segment of HEC chains than that of the corresponding linear chain.

Electrical conductivity of polyvinyl alcohol/carboxymethyl cellulose doped by zinc oxide and hematite nanoparticles for optoelectronics devices

This research explores polymer nanodielectrics, a category of materials where nanoceramic fillers are incorporated into polymers. These hybrid materials are gaining significant interest due to their tunable optical and electrical properties, making them potentially well-suited for applications in flexible optoelectronic and organic electronic devices. Polyvinyl alcohol (PVA), Carboxymethyl cellulose (CMC), zinc oxide (ZnO), and hematite (Fe2O3) nanoparticles (NPs) have been used to create nanocomposite materials in order to improve their optical and electrical characterization. Physical methods have been used to investigate the effects of varying hematite nanoparticle contents on the optical and electrical characterization of the prepared films. XRD analysis indicated a reduction in the crystalline character of the PVA/CMC blend following the incorporation of ZnO/Fe2O3 nanoparticles (NPs). FTIR data approved the interaction between the PVA/CMC composite and the ZnO/Fe2O3, leading to a decrease in intermolecular interactions within the polymeric matrix and coordination with the ZnO/Fe2O3. Electrical analysis obtained an enhancement in σac values with the rise of ZnO/Fe2O3 NPs content up to 30 min of laser ablation times in the polymeric nanocomposite due to the high content of ZnO/Fe2O3 NPs that were added to the PVA/CMC hybrid polymer matrix. The findings from this study suggest the promise of these materials for applications in high-performance batteries, supercapacitors, or other next-generation energy storage and conversion devices.

Comparative structural analysis of anhydrous and monohydrated polymorphs of diclofenac diethylammonium: Implications for stability, dissolution, and bioavailability

Diclofenac diethylammonium belongs to the class of non-steroidal anti-inflammatory drugs, and it is widely used to relieve pain and reduce systemic inflammation. This drug exists in polymorphic forms, which can directly affect the ability to process the drug, as well as drug product dissolution, stability, and bioavailability. Considering the worldwide regulatory guidance for polymorphs in drug substances, a detailed structural analysis of two polymorphs exhibiting the anhydrous and monohydrated structures of diclofenac diethylammonium is presented here, using the supramolecular arrangement and its relationship with structural-physicochemical properties. The polymorph’s structures show conformational differences in the carboxylic group caused by coordinated water molecules presented in the monohydrated polymorphic structure. Both polymorphs have the supramolecular arrangement stabilized by NH···O and CH···Cl intermolecular interactions, but the monohydrated molecule presents a strong OH···O intermolecular interaction due to the presence of a water molecule. Hirshfeld surface analysis showed CH···π and π···π contacts in the anhydrous and monohydrated polymorphs, respectively. Theoretical results, including solvent effect with explicit and implicit approaches for water, indicated the kinetic stability of the diclofenac diethylammonium drug and showed susceptible electrophilic attacks occurring in the region close to the carbonyl oxygen atom.

Exploration of supramolecular interactions, Hirshfeld surface, FMO, molecular electrostatic potential (MEP) analyses of pyrazole based Zn(II) complex

The supramolecular interactions of title compound [Zn(HL2)](ClO4)2(MeOH)2] (1) where, HL2=((Z)-N’-(5-methyl-1H-pyrazole-3-carbonyl)pyrazine-2-carbohydrazonamide) are explored in detail. With a detailed scrutiny of visualizing of title compound 1, the crystal packing is mainly directed by strong hydrogen bonding interactions observed N–H⋯N and N–H⋯O but, in addition, weak interactions such as C–H⋯π, π⋯π are also sighted to stabilize the crystal self-assembly. Electronic structure of the complex is determined using DFT calculations at B3LYP level with mixed basis set. Theoretically calculated structural parameters are in good match with the experimentally obtained parameters from XRD. TDDFT calculation is performed to simulate the UV–Vis absorption spectra of the complex. Molecular reactivity and stability of the complex has been assessed through frontier molecular orbital analysis and also through evaluation of molecular electrostatic potential (MEP). Hirshfeld surface analysis, which uses molecular surface contours and 2D fingerprint plots to visually analyze intermolecular interactions in crystal structures, has been used to examine molecular morphologies. The Hirshfeld surface and fingerprint plots are accompanied by crystal structure analysis allowed for the discovery of the important intermolecular interactions.

Biological Evaluation of a Novel Schiff Base Ligand as an Antioxidant Agent: Synthesis, Characterization and DFT Computations of its Ni(II) and Cu(II) Complexes

By condensation reaction in methanolic medium, a novel ligand using methoxy substituted amine and 5-bromosalicylaldehydic was synthesized. Then, its Cu- and Ni- complexes were also prepared under same experimental conditions. The final desired compounds, with high obtained yields, have been characterized and well discussed by EA-CHN, UV-Vis., FT-IR, NMR, SEM-EDX and MS spectrometry. The structure of the ligand was confirmed by X-ray crystallography showing an interesting intramolecular hydrogen bond and also intermolecular interactions (Br...CArom. and CH/π-type). The electronic properties were quantified by density functional theory (DFT) calculations using DFT- B3LYP/6-31G (d,p) level basis set. The molecular structures, geometrical parameters, chemical reactivity, stability, molecular electrostatic potential (MEP) and Mulliken atomic charges were computed to identify the chemical reactive sites on the molecular surface. The antioxidant activities were studied theoretically involving various parameters such as bond dissociation enthalpy (BDE), ionization potentials (IPs), proton affinities (PA), proton dissociation enthalpy (PDE), electron transfer enthalpy (ETE) and radical stabilization energy (RSE). Experimentally, the antioxidant activities were also studied by using 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric ion reducing antioxidant power (FRAP) and nitric oxide scavenging (SNP) methods. The computational study of antioxidant activity is well correlated with their experimental results.

Classical tribology and charge-energy evolution theory cooperate to determine nitrided ceramic coating/metal substrate interfacial friction

Who governs interfacial friction, classical tribology theory or charge-energy theory? Since it was widely recognized that the origin of friction is interatomic forces, attention has gradually shifted towards the characteristics of local nanoscale interfaces. The new theory believes the charge density evolution during the friction process has more significant attributes in determining the friction properties. Here, we discuss the frictional failure mechanisms at the ceramic/metal interface formed after the nitriding. The increase in N-doped interface friction is supported by classical friction theory and corresponds to high interface adhesion work. On the other hand, the H-doped interface with the lowest adhesion work exhibits the highest friction. Unlike other interface systems (metallic bonding), the failure interface after H doping is an ionic bonding interface. Stronger ionic bonds are formed and broken in relative sliding, significantly increasing charge density. This emphasizes the crucial role of charge density in this process, aligning with the principles of the new theory. Nevertheless, the classical friction theory can still be used when measuring friction properties of the interface with the same chemical bonds, and it may be more convincing than the new theory. Overall, these research results reveal the intrinsic origin of H/N's influence on TiN/Ti friction properties and provide new insights into understanding natural failures at the nanometer level.

Nondestructive frozen protein ink: Antifreeze mechanism, processability, and application in 3D printing

Antifreeze peptide (AFP) including in frozen protein ink is an inevitable trend because AFP can make protein ink suitable for 3D printing after freezing. AFP-based surimi ink (ASI) was firstly investigated, and the AFP significantly enhanced 3D printability of frozen surimi ink. The rheological and textural results of ASI show that the τ0, K, and n values are 321.14 Pa, 2.2259 × 105 Pa·sn, and 0.19, respectively, and the rupture strength of the 3D structure is up to 217.67 g. Circular dichroism, intermolecular force, and differential scanning calorimeter show ASI has more undenatured protein after freezing when compared that surimi ink (SI), which was denatured, and the α-helix changed to a β-sheet due to the destruction of hydrogen bonds and the exposure of hydrophobic groups. The water distribution, water holding capacity, and microstructure indicate that ASI effectively binds free water after freezing, while SI has weak water binding capacity and a large amount of free water is formed. ASI is suitable for 3D printing, and can print up to 40.0 mm hollow isolation column and 50.0 mm high Wuba which is not possible with SI. The application of AFP provides guidance for 3D printing frozen protein ink in food industry.

Characterization of Composite Materials Using Carbon Nano Tube Carboxy Group Introduction and Aluminum Oxide Synthesis

The high integration and high density of semiconductor packages are generating increased heat in electronic devices, leading to issues such as reduced lifespan and malfunctions in electronic devices. In response, research on thermal interface materials is being conducted to address heat generated from heat sources, and various studies, particularly those applying carbon nano tube, are notable in this regard. However, in the case of carbon nano tube, there are challenges in industrial application due to the occurrence of cohesive forces through van der Waals interactions. Therefore, in this study, the characteristics were analyzed through the formation of carbon nano tube carboxyl groups (–COOH) and the synthesis of aluminum oxide via chloride (–COCl) formation. After the chloride process, a functional group –COCl was confirmed at 430 cm−1. It was confirmed that the electrical properties were improved as a result of the CNT, CNT carboxyl, and chloride process. It is believed that the electrical properties improved as impurities were removed during the acid treatment process. In addition, it is believed that the electrical properties were improved due to the increase in intermolecular forces between CNTs. Through this, it is determined that the application of carbon nano tube and aluminum oxide composite materials can be highly beneficial for thermal conductivity heat dissipation filler applications.

The pH dependent structural and viscoelastic behavior of Ovomucin-Complex isolated from egg white under alkaline conditions

Ovomucin-Complex (OVM) is responsible for providing the natural gel-like properties of egg white, especially in alkali-induced egg white gels. In this study, OVM was modified by alkaline to produce gel-type materials. The structure, physicochemical and viscoelastic properties of OVMs under different pH (7–12) were probed using FTIR, HPLC, SEM, CLSM and rheometer. The results of rheological measurements in linear viscoelastic region revealed that alkaline modified OVMs exhibited a soft viscoelastic gel in alkaline conditions, with the transition occurring near pH 8, compared with a viscoelastic solution at neutral pH. In addition to the pH-dependent gelation behavior of OVMs, further rheological studies under nonlinear deformations reveal shear thinning and an apparent yield stress, which were also highly affected by pH. The results from HPLC and molecular interactions suggest that the alkaline modification led to the depolymerization of OVMs in alkaline conditions, enhancing the formation of intermolecular disulfide bonds, electrostatic force and hydrophobic interactions. The differences in these mechanical properties were also reflected in the OVM structure. The SEM and CLSM images demonstrated that the arrangement of gel pores under pH 10 conditions is denser and well-distributed than those under other conditions. The FTIR results verified that alkaline modification leads to the decreased content of β-sheet. Nevertheless, prolonged exposure to pH 12.0 resulted in a gradual liquefaction of the gel due to increased electrostatic repulsion and surface hydrophobicity, as well as the reduced disulfide bond and an increase in the disordered structure. These findings provide a novel insight for the development of mucin gel foods.

Investigation of mechanical, microscopic, and leaching properties of coal-based solid waste geopolymer mortar activated by soda residue and phosphogypsum

In this study, coal-based solid waste geopolymer mortar (SWCB) was prepared by using granulated ground blast-furnace slag (GGBS) and coal gasification coarse slag (CGCS) as precursors, and soda residue (SR) and phosphogypsum (PG) as activators, with gangue sand (GS) utilized as an inert filler. The corresponding compressive strength, fluidity, ion leaching, and microstructure of the developed SWCB were systematically investigated under varying solid contents, binder-to-sand ratios, and activator ratios. The findings suggest that the incorporation of activators promoted the dissolution of the silicon-aluminum phase in GGBS and CGCS into Al(OH)4−, [SiO(OH)3]−, and [SiO2(OH)2]2−, which could subsequently react with the Ca2+ and SO42− released by PG, forming AFt and C-(A)-S-H, thereby playing a crucial role in enhancing matrix strength. AFt was the predominant hydration product in the early reaction stage. The morphology of the AFt phase evolved from needle-like or filamentous to fine and coarse rods as hydration progressed. Initially, the formation of C-(A)-S-H gel increased with rising activator content before decreasing. The optimal synergy between AFt and C-(A)-S-H was observed at an activator content of 30 %. However, the growth of gypsum crystals was hindered when the activator content surpassed 30 %, resulting in a plate-like or columnar morphology. C-(A)-S-H gel exhibited remarkable adsorption capability towards P atoms attributed to intermolecular Van der Waal's forces, enabling simultaneous physical encapsulation of P atoms, while Cl element immobilization was primarily attributed to the contribution of SiOH sites to Cl adsorption.

Mechanochromism of π-conjugated borate derivatives and the effect of intermolecular non-covalent forces on molecular packing and mechanochromic property

We prepared three π-conjugated pinacol borate derivatives anthryl dioxaborolane (ANB), pyrenyl dioxaborolane (PYB) and perylenyl dioxaborolane (PEB) based on anthracene, pyrene and perylene moieties, and studied their optical properties in solid and solution. Interestingly, the three molecules were structurally similar, yet exhibited different optical properties and mechanochromic behavior. Crystal structure studies showed that the mechanical fluorescent response of ANB, PYB and PEB were closely related to the molecular packing modes. Although there were multiple π-π and σ-π interactions in all three molecules, the conjugation degree of ANB was relatively low, resulting in a weak π-π interaction. Therefore, the effective partial parallel packing between adjacent ANB could not form in the initial state, and external mechanical stimulation could not induce the change of optical properties. In PYB and PEB molecules with a high conjugation degree, the π-π interaction was stronger. A partial parallel packing state was formed between the molecules under the synergistic action of π-π and σ-π interaction. Under external disturbance, the relative slippage between molecules was easy to occur. Thus, the characteristic static excimer fluorescence was displayed due to the enhancement of parallel packing. Since the intermolecular interactions of PYB and PEB were a kind of weak non-covalent forces, the packing state changed by external force could return to the initial state at room temperature, showing reversible mechanochromic characteristic. This kind of room temperature reversible force sensitive material constructed by weak non-covalent interactions was expected to be applied and popularized in the fields of encrypted communication and anti-counterfeiting display.

The effect of protein-glutaminase from Chryseobacterium proteolyticum on physicochemical and functional properties of high-temperature soybean meal protein

Protein-glutaminase (EC 3.5.1.44, PG) can significantly improve the functional properties of food proteins. However, the low yield of PG has limited industrial applications. Results showed that 0.02 % tea saponin could increase the PG yield by 18.93 %. The transcription level of the PG gene was significantly enhanced, which promoted the extracellular secretion of PG through an increase in membrane permeability. On this basis, PG was used to modify high-temperature soybean meal protein (HSMP) due to its poor properties. In this study, the deamidation degree (DD) of PG-modified HSMP was optimized to 58.61 % by the response surface method. HSMP with different DD was prepared and its physicochemical and functional properties were studied. After PG treatment, the intermolecular repulsive force of HSMP increased, the particle size distribution became uniform, and the solution system was more stable. In addition, the surface morphology of HSMP gradually became loose and porous. The solubility of HSMP significantly improved, reaching 11.34 times that of untreated HSMP at pH 5.00. Meanwhile, the emulsifying and foaming capacity of HSMP significantly improved, but the foaming stability was reduced.

Structural and computational insights into two completely unanticipated Cu(II) and Ni(II) complexes derived from a bifunctional salamo-type bis(pyridine)-arm ligand

A bifunctional Salamo-type bis(pyridine)-arm ligand H2L (4,4′-Methyl-6,6′-pyridinenitrilomethylidyne-2,2′-[ethylenedioxybis(nitrilomethylidyne)]diphenol) was designed and synthesized, which can react with Cu(II) and Ni(II) nitrates to hydrolyze & break the C = N double bonds of new ligand H2L′ (4,4′-Methyl-6,6′-formal-2,2′-[ethylenedioxybis(nitrilomethylidyne)]diphenol). The ligand reacted with Cu(II) and Ni(II) salts to form respectively complexes [Cu(L′)] (1) and [Ni2(L′)(H2O)2](NO3)2 (2). They were elucidated by single crystal X-ray method. Many important noncovalent interactions, such as intramolecular hydrogen bonding, intermolecular hydrogen bonding and π···π stacking interactions, can be observed in the crystal structures of the two complexes. IR & UV–Vis absorbent spectroscopic analysis showed that the ligand unit is involved in the coordination with copper(II) and nickel(II) atoms, and ultraviolet titration and fluorescence titration spectra verified that the coordinating radios of the two complexes formed in liquid phase are in accordance with those of single-crystal X-ray diffraction. Through DFT theoretical calculations and electrostatic potential analyses (MESP) of the ligand and its complexes, the configuration of the ligand at the lowest energy were deeply understood, and it was demonstrated that the coordination reaction at salamo sites requires a great torsional force, and the weak intermolecular interaction force and the energy gaps of HOMO-LUMO orbitals were profoundly discussed, and the Cu(II) and Ni(II) complexes exhibit anomalous fluorescence enhancement behaviors.

Two-tailed modification module tuned steric-hindrance effect enabling high therapeutic efficacy of paclitaxel prodrug nanoassemblies

Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy, mainly comprise drug modules, response modules and modification modules. However, existing studies usually compare the differences between single types of modification modules, neglecting the impact of steric-hindrance effect caused by chemical structure. Herein, single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs (P-LAC18 and P-BAC18), and the in-depth insights of the steric-hindrance effect on prodrug nanoassemblies were explored. Notably, the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance. Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents, showing faster drug release and stronger antitumor efficacy, but with poorer safety. In contrast, two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics, tumor accumulation and safety due to the good size stability, thus ensuring equivalent antitumor efficacy at tolerance dose. These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structure-activity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.