Exploring the Correlation between Azido-Tetrazolo Tautomerizations and Isomer Structures: Electron Density of Bonding N Atoms and N-N Bond Polarity.

Azido-tetrazolo tautomerizations between azido N-heteroaromatic compounds and tetrazole-fused energetic materials can produce a new generation of high-energy density compounds. Density functional theory (DFT) computations are performed to explore the relationship between reaction barriers and electron densities of bonding N atoms, i.e., the terminal N1 and heterocyclic N2 atoms, for six reported tautomerizations. The results reveal four linear correlations between reverse reaction barriers (Gr) and the electron densities of N1 and N2 atoms in the product. N1 electron density (ρN1) and N-N bond polarity, as measured by the difference between the electron densities on the two N atoms (ΔρN = ρN1 - ρN2) in products, are inversely proportional to the reverse reaction barriers. They are also proportional to the energy barrier differences between the forward and reverse reactions (ΔG = Gf - Gr). Polar solvents, including DMSO, water, and acetone, can effectively increase the reverse reaction barriers (Gr) by improving the stability of products. This regularity is further confirmed by its application to four additional tautomerizations and can be used to screen out unfavorable azido-tetrazolo tautomerization reactions and increase the success rate of such synthesis.

Exploring the thermal decomposition and detonation mechanisms of 2,4-dinitroanisole by TG-FTIR-MS and molecular simulations.

2,4-dinitroanisole (DNAN), an insensitive explosive, has replaced trinitrotoluene (TNT) in many melt-cast explosives to improve the safety of ammunition and becomes a promising material to desensitize novel explosives of high sensitivity. Here, we combine thermogravimetric-Fourier transform infrared spectrometry-Mass spectrometry (TG-FTIR-MS), density functional theory (DFT), and ReaxFF molecular dynamics (MD) to investigate its thermal decomposition and detonation mechanisms. As revealed by TG-FTIR-MS, the thermal decomposition of DNAN starts at ca. 453 K when highly active NO2 is produced and quickly converted to NO resulting in the formation of a large amount of Ph(OH)(OH2)OCH3+. DFT calculations show that the activation energy of DNAN is higher than that of TNT due to the lack of α-H. Further steps in both thermal decomposition and detonation reactions of the DNAN are dominated by bimolecular O-transfers. ReaxFF MD indicates that DNAN has a lower heat of explosion than TNT, in accordance with the observation that the activation energies of polynitroaromatic explosives are inversely proportional to their heat of explosion. The inactive -OCH3 group and less nitro groups also render DNAN higher thermal stability than TNT.

How are N-methylcarbamates encapsulated by ß-cyclodextrin: insight into the binding mechanism.

Guest molecules containing chromophore groups encapsulated by ß-cyclodextrin (ß-CD) generate circular dichroism (CD) signals, which enables a preliminary prediction of their binding modes. However, the accurate determination of the representative binding conformation (RC) remains a challenging task due to the complex conformational space of these host-guest systems. Here, we combine a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/CSM) with induced circular dichroism (ICD) data (N. L. Pacioni, A. B. Pierini and A. V. Veglia, Spectrochim. Acta A Mol. Biomol. Spectrosc., 2013, 103, 319-324.) to explore the binding mechanism of ß-CD with four N-methylcarbamate molecules: promecarb (PC), bendiocarb (BC), carbaryl (CY) and carbofuran (CF). In aqueous solution, their stability decreases as: PC > BC > CY > CF. Comparing the ECD spectra computed from TD-DFT with the ICD data can help eliminate many common binding configurations and identify the RC. The host-guest binding affinities (BAs) estimated using a ONIOM2(B971:PM6)/SMD model reproduce the measured binding trend, reveal the competition between the non-covalent interaction and solvent effect and explain the large difference in their binding modes. We also examine the fluctuations in the computed BA using similar structures.

A single-wavelength excited NIR fluorescence probe for distinguishing GSH/H2S and Cys/Hcy in living cells and zebrafish through separated dual-channels.

Biothiols and hydrogen sulfide, as critical sulfur-containing reactive substances, serve essential functions in various human pathological processes, making it challenging to simultaneously distinguish them due to their similar reactivity and structures (-SH). Here, we rationalized the development of a single-wavelength excitation near-infrared (NIR) fluorescence probe, FC-NBD, for distinguishing GSH/H2S and Cys/Hcy by separated fluorescence dual channels. In this probe, FC-NBD, composed of coumarin-benzopyrylium derivatives linked with nitro benzoxadiazole (NBD) via ether bonds, could quantitatively and selectively distinguish GSH/H2S and Cys/Hcy with a low limit of detection (LOD) of 0.199/0.177 µM and 0.106/0.076 µM, respectively. As expected, under single-wavelength excitation (470 nm), FC-NBD demonstrated distinctly separable green and NIR fluorescence emissions towards Cys/Hcy at 550 and 660 nm, but only exhibited a noticeable NIR fluorescence emission towards GSH/H2S at 660 nm. Moreover, FC-NBD could simultaneously visualize and discriminate GSH/H2S and Cys/Hcy in living cells as well as zebrafish through green and NIR channels at a single excitation wavelength.

Evaluating the impact of Hartree-Fock exact exchange on the performance of global hybrid functionals for the vertical excited-state energies of fused-ring electron acceptors using TD-DFT.

The acceptor-donor-acceptor structured fused-ring electron acceptors (FREAs) have piqued interest for organic solar cells. We herein employ time-dependent density functional theory to evaluate the effect of Hartree-Fock exact exchange (HFX) on the performance of 16 global hybrid functionals for computing the maximum absorption wavelengths (λver-theo) and the vertical excitation energies (Ever-theo) of 34 molecules. We customize the HFX ratio in the functionals used to perform an in-depth analysis of its impact on the Ever-theo values. The computed λver-theo values strictly follow an inverse proportionality to the HFX percentage. The performance of the methods with the same ratio of HFX is almost identical, such as B3LYP, B3PW91, and mPW3PBE containing 20% HFX. The performance enhances with a relatively higher HFX ratio of 21% in X3LYP, B971, B972, and 22% in B98 giving smaller deviations. APF and APFD containing 23% HFX provide the smallest deviations for all compounds, with a mean signed error limited to 0.02 eV and a mean absolute error (MAE) of 0.06 eV. The performance drops using M06 and M05 with comparatively higher HFX ratios providing MAE values of 0.07 eV and 0.1 eV, respectively. M06-2X with 54% HFX provides the largest MAE value of 0.35 eV. The lowest obtained MAE is 0.06 eV at 23 to 25% HFX in most of the functionals considered in this study, suggesting that these are the optimal values for the prediction of excitation energies of FREAs. It has also been found that global hybrids seem to be more efficient for larger-sized molecules with a smaller bandgap.

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4-Oxadiazole-2-Thiol Derivatives.

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29 µM for AChE and 21.83±0.39 to 39.43±0.44 µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

Enhanced mechanical properties and biocompatibility on BC/HAp composite through calcium gluconate fortified bacterial.

Bacterial cellulose/hydroxyapatite (BC/HAp) composite is an outstanding candidate for bone tissue engineering. The conventional biomimetic mineralization method takes a long time with unsatisfactory mechanical properties and biocompatibility. Herein, we modified the BC by changing the carbon source to calcium gluconate during the biosynthesis process of BC by bacteria, providing nucleation sites for further mineralization in simulated body fluid. Results show spherical porous HAp in the size of 100-200 nm was fully filled in the three-dimensional network structure of BC nanofibers uniformly within five days of mineralization. Molecular dynamics simulation shows that the aggregation of cellulose units in aqueous solution can enhance the adsorption of calcium ions. By this means, we significantly improved the mechanical properties and biocompatibility of the BC/HAp composite, as well as simplified the preparation process, compared to conventional method, which, therefore, suggests, it could be further studied for biomedical applications such as bone tissue engineering.

Tandem CuAAC/Ring Cleavage/[4 + 2] Annulation Reaction to Synthesize Dihydrooxazines and Conversion to 2-Aminopyrimidines.

A tandem CuAAC/ring cleavage/[4 + 2] annulation reaction of terminal ynones, sulfonyl azides, and oximes has been developed to synthesize functionalized dihydrooxazines under mild conditions. In particular, intermediate N-sulfonyl acylketenimines are the first example of a 4π-system participating in [4 + 2] cycloadditions, and dihydrooxazines can convert to 2-aminopyridines through ring cleavage under basic conditions.

Evaluating the nature of the vertical excited states of fused-ring electron acceptors using TD-DFT and density-based charge transfer.

Acceptor-donor-acceptor structured fused-ring electron acceptors (FREAs) are the most efficient electron acceptors used in organic solar cells. We use density functional theory (DFT), its time-dependent version (TD-DFT), and an intra-molecular charge transfer index to evaluate the nature of the excited states of FREAs. Typically, several efficient electronic transitions contribute to the absorption spectra of FREAs. An investigation of every efficient electronic transition of each FREA is performed based on the electronic density variation in the donor and acceptor moieties of the molecules upon absorbing solar photons. Not all these transitions are equivalent for light-to-electricity conversion. The first transition contributes the most to the absorption spectra. This transition is intense and extremely efficient for light-to-electricity conversion, giving a higher value of intra-molecular charge transfer. For certain effective transitions of FREAs, the phenyl rings in the donor unit behave as the electron-donating units, such as IDT-NTI-2EH, BTCN-M, and MeIC. The foremost finding of the present research work is that the furthermost strong electronic transitions are not essentially the most effective ones for the conversion of sunlight into electricity.

Oxygen vacancy mediated single unit cell Bi2WO6 by Ti doping for ameliorated photocatalytic performance.

Crystal defects are crucially important in semiconductor photocatalysis. To improve the reactivity of photocatalysts and attain desirable solar energy conversion, crystal defect engineering has gained considerable attention in real catalysts. Herein, we engineered crystal defects and mediate oxygen vacancies in host Bi2WO6 crystal lattice via varying content of Ti dopant to fabricate single-unit-cell layered structure, resulting in enhanced visible-light-driven photocatalytic efficiency. Density functional theory (DFT) calculations verified that the substitution of Bi cation in the crystal structure of Bi2WO6 can induce a new defect level, and increase the density of states (DOS) at the valence band maximum, which not only improve the charge dynamic but also the electronic conductivity. Remarkably, the single-unit-cell layers Ti-doped Bi2WO6 structure casts profoundly improved photocatalytic performance towards ceftriaxone sodium degradation, Cr(VI) reduction, and particularly higher photocatalytic H2 production rate, with a 5.8-fold increase compared to bulk Bi2WO6. Furthermore, the photoelectrochemical measurements unveil that the significantly higher charge migration and charge carrier dynamic counts for the elevated photocatalytic performance. After careful examination of experimental results, it was proved that the Ti doping mediated crystal defects, and engendered oxygen vacancies are critically important for controlling the photocatalytic performance of Bi2WO6.

TD-DFT benchmark for UV-visible spectra of fused-ring electron acceptors using global and range-separated hybrids.

Non-fullerene acceptors, especially acceptor-donor-acceptor structured fused-ring electron acceptors (FREAs), have attracted widespread attention in organic solar cells because of their versatile molecular design in fine-tuning light absorption and energy levels. We report the accuracy of Time-Dependent Density Functional Theory (TD-DFT) for FREAs by comparing their theoretically predicted vertical absorption wavelength (λver-abso) with the experimental maximum absorption (λmax). The λver-abso values of 50 molecules obtained from major types of FREAs have been investigated using TD-DFT by considering the solvent effects. The values of λver-abso predicted with a pure density functional (PBE), global hybrids (B3LYP and PBE0) and range-separated schemes (CAM-B3LYP and LC-ωPBE) follow the exact exchange percentage included at an intermediate inter-electronic distance. Global hybrids outperform all other schemes. The mean absolute error provided is 22 nm by PBE0 and 38 nm by B3LYP for the whole set of molecules. The maximum deviation of 92 nm provided by B3LYP and 69 nm provided by PBE0 confirms that PBE0 is more appropriate for predicting the absorption wavelengths when designing new FREAs. By applying linear regression analysis to obtain the calibration curve, we found that the range-separated methods provide an equal or even more consistent description of FREA excited states. For the whole set of molecules, linearly corrected data yield an average error of 25 and 27 nm for CAM-B3LYP and LC-ωPBE, respectively. Consequently, when a statistical analysis technique is applicable for a certain series of FREAs, a theoretical method permits a chemically comprehensive and empirically good explanation of UV/Vis spectra for newly-designed FREAs.

Organocatalyzed Solvent Free and Efficient Synthesis of 2,4,5-Trisubstituted Imidazoles as Potential Acetylcholinesterase Inhibitors for Alzheimer's Disease.

The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives 3a-3m. The compounds 3a-3m were synthesized by one pot condensation reaction of substituted aromatic aldehydes, benzil, and ammonium acetate in good to excellent yields (74-96 %). To explore the potential of these compounds against Alzheimer's disease, their inhibitory activities against acetylcholinesterase (AChE) were evaluated. In this series of compounds, compound 3m, bearing one ethoxy and a hydroxy group on the phenyl ring on 2,4,5-trisubstituted imidazoles, proved to be a potent AChE inhibitor (102.56±0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the compounds 3m, 3e, 3k, 3c, 3a, 3d, 3j, and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the compound 3m forms an H-bond with the oxygen atom of the residue (i. e., THR121) which has a bond length of 3.051 Å.

Synthesis and evaluation of a novel 'off-on' chemical sensor based on rhodamine B and the 2,5-pyrrolidinedione moiety for selective discrimination of glutathione and its bioimaging in living cells.

A new "turn-on" fluorescent probe, RDMBM, based on the rhodamine B dye and the 2,5-pyrrolidinedione moiety was synthesized and characterized. Its sensing behavior toward various amino acids was evaluated via UV-vis and fluorescence spectroscopic techniques. The observed spectral changes showed that RDMBM displays high selectivity and sensitivity toward GSH in MeOH/H2O (1:2, v/v, pH 7.40, Tris-HCl buffer, 1 mM) solution and that it undergoes 1:1 covalent binding with GSH. More importantly, the hydrogenation and ring-opening of the nitrogen atom in the spirane structure of rhodamine B derivatives were tightly bound to the induction effects of different groups. Furthermore, fluorescence imaging applications demonstrated that RDMBM can be successfully used for the detection of GSH in human breast cancer cells MCF-7.

Metal-to-Ligand Charge-Transfer-based Visual Detection of Alkaline Phosphatase Activity.

The ability to directly detect alkaline phosphatase (ALP) activity in undiluted serum samples is of great importance for clinical diagnosis. In this work, we report the use of the distinctive metal-to-ligand charge-transfer (MLCT) absorption properties of the Cu(BCA)2+ (BCA = bicinchoninic acid) reporter for the visual detection of ALP activity. In the presence of ALP, the substrate ascorbic acid 2-phosphate (AAP) can be enzymatically hydrolyzed to release ascorbic acid (AA), which in turn reduces Cu2+ to Cu+. Subsequently, the complexation of Cu+ with the BCA ligand generates the chromogenic Cu(BCA)2+ reporter, accompanied by a color change of colorless-to-purple of the solution with a sharp absorption band at 562 nm. The underlying MLCT-based mechanism has been demonstrated on the basis of density functional theory (DFT) calculations. Needless of any sequential multistep operations and elaborately designed colorimetric probe, the proposed MLCT-based method allows for a fast and sensitive visual detection of ALP activity within a broad linear range of 20 - 200 mU mL-1 (R2 = 0.999), with a detection limit of 1.25 mU mL-1. The results also indicate that it is highly selective and has great potential for the screening of ALP inhibitors in drug discovery. More importantly, it shows a good analytical performance for the direct detection of the endogenous ALP levels of undiluted human serum samples. Owing to the prominent simplicity and practicability, it is reasonable to conclude that the proposed MLCT-based method has a high application prospect in clinical diagnosis.

A combined experimental and DFT mechanistic study for the unexpected nitrosolysis of N-hydroxymethyldialkylamines in fuming nitric acid.

The reaction of dimorpholinomethane in fuming HNO3 was investigated. Interestingly, the major product was identified as N-nitrosomorpholine and a key intermediate N-hydroxymethylmorpholine was detected during the reaction by 1H-NMR tracking which indicates that the reaction proceeds via an unexpected nitrosolysis process. A plausible nitrosolysis mechanism for N-hydroxymethyldialkylamine in fuming nitric acid involving a HNO3 redox reaction is proposed, which is supported by both experimental results and density functional theory (DFT) calculations. The effects of ammonium nitrate and water on the nitrosolysis were studied using different ammonium salts as additives and varying water content, respectively. Observations show the key role of ammonium ions and a small amount of water in promoting the nitrosolysis reaction. Furthermore, DFT calculations reveal an essential point that ammonia, merged from the decomposition of the ammonium salts, acts as a Lewis base catalyst, and the hydroxymethyl group of the substrate participates in a hydrogen-bonding interaction with the NH3 and H2O molecules.

Fluorescence quenching based alkaline phosphatase activity detection.

Simple and fast detection of alkaline phosphatase (ALP) activity is of great importance for diagnostic and analytical applications. In this work, we report a turn-off approach for the real-time detection of ALP activity on the basis of the charge transfer induced fluorescence quenching of the Cu(BCDS)22- (BCDS = bathocuproine disulfonate) probe. Initially, ALP can enzymatically hydrolyze the substrate ascorbic acid 2-phosphate to release ascorbic acid (AA). Subsequently, the AA-mediated reduction of the Cu(BCDS)22- probe, which displays an intense photoluminescence band at the wavelength of 402nm, leads to the static quenching of fluorescence of the probe as a result of charge transfer. The underlying mechanism of the fluorescence quenching was demonstrated by quantum mechanical calculations. The Cu(BCDS)22- probe features a large Stokes shift (86nm) and is highly immune to photo bleaching. In addition, this approach is free of elaborately designed fluorescent probes and allows the detection of ALP activity in a real-time manner. Under optimal conditions, it provides a fast and sensitive detection of ALP activity within the dynamic range of 0-220mUmL-1, with a detection limit down to 0.27mUmL-1. Results demonstrate that it is highly selective, and applicable to the screening of ALP inhibitors in drug discovery. More importantly, it shows a good analytical performance for the direct detection of the endogenous ALP levels of undiluted human serum and even whole blood samples. Therefore, the proposed charge transfer based approach has great potential in diagnostic and analytical applications.

Organocatalyzed and mechanochemical solvent-free synthesis of novel and functionalized bis-biphenyl substituted thiazolidinones as potent tyrosinase inhibitors: SAR and molecular modeling studies.

Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of Schiff's bases bearing different substituents with thioglycolic acid produces a variety of thiazolidinones derivatives in good to excellent yield. In vitro inhibition studies against mushroom tyrosinase of these thiazolidinone analogues revealed that many of them possessed good to excellent tyrosinase inhibition at low micro-molar concentrations. In particular, six compounds exhibited potent inhibitory potential with IC50 values ranging from 0.61 ± 0.31 to 21.61 ± 0.11 µM as compared with that of standard kojic acid (IC50 6.04 ± 0.11 µM). Further molecular docking studies revealed that the thiazolidinones moiety plays a key role in the inhibition mechanism by well fitting into the enzyme bounding pocket.

Facile colorimetric assay of alkaline phosphatase activity using Fe(II)-phenanthroline reporter.

We report a versatile approach for the colorimetric assay of alkaline phosphatase (ALP) activity based on the distinctive metal-to-ligand charge-transfer (MLCT) absorption properties of Fe(II)-phenanthroline reporter. In the presence of ALP, the applied substrate ascorbic acid 2-phosphate is enzymatically hydrolyzed to produce ascorbic acid, which then reduces Fe3+ to Fe2+. The complexation of Fe2+ with the bathophenanthroline disulfonate (BPS) ligand generates a blood-red Fe(BPS)34- reporter, which is characterized by an intense MLCT absorption band at 535 nm in the visible range. Under optimal conditions, the spectral output exhibits a good quantitative relationship with ALP activity over the range of 0-220 mU mL-1 with a detection limit of 0.94 mU mL-1. Moreover, the activity of ALP can also be conveniently judged through naked-eye observations. Results indicate that it is highly selective and can be applied to the screening of ALP inhibitors. In addition, it has been successfully employed to detect the endogenous ALP level of undiluted human serum samples, with a detection limit of 1.05 mU mL-1 being achieved. This approach avoids any elaborately designed substrates and holds considerable simplicity and flexibility for reporter design. This study broadens the horizon of the applications of phenanthroline-based transition metal complexes. Furthermore, an efficient and practical method like this has the potential to be widely used in clinical applications and in the point-of-care testing.

Turn-On Colorimetric Platform for Dual Activity Detection of Acid and Alkaline Phosphatase in Human Whole Blood.

The activity detection of acid phosphatase (ACP) and alkaline phosphatase (ALP) is of great importance to the diagnosis and prognosis of related diseases. In this work, we report for the first time a turn-on colorimetric platform for the activity detection of ACP and ALP, by exploiting Cu(BCDS)22- (BCDS=bathocuproinedisulfonate) as the probe. The presence of ACP or ALP dephosphorylates the substrate ascorbic acid 2-phosphate to produce ascorbic acid, which then reduces Cu(BCDS)22- into Cu(BCDS)23- , leading to a turn-on spectral absorption at 484 nm and a dramatic color change of the solution from colorless to orange-red. The underlying metal-to-ligand charge-transfer mechanism has been demonstrated by quantum mechanical computations. This platform allows a rapid, sensitive readout of ACP and ALP activities within the dynamic range from 0 to 220 mU ml-1 . In addition, it is highly immune to false-positive results and also highly selective. More importantly, it is applicable in the presence of human serum and even whole blood samples. These results demonstrate that our platform holds great potential in clinical practices and in the point-of-care analysis.

Dual pH-Mediated Mechanized Hollow Zirconia Nanospheres.

We demonstrate for the first time how to assemble mechanized hollow zirconia nanospheres (MHzNs), consisting of hollow mesoporous zirconia nanospheres (HMZNs) as nanoscaffolds and supramolecular switches anchored on the exterior surface of HMZNs. The remarkable advantage of substitution of HMZNs for conventional mesoporous silica nanoscaffolds is that HMZNs can suffer the hot alkaline reaction environment, which provides a novel strategy for functionalization and thus achieve dual pH-mediated controlled release functions by simple and practicable assembly procedure. Under neutral solution, cucurbituril[7] (CB[7]) macrocycles complexed with propanone bis(2-aminoethyl)ketal (PBAEK) to form [2]pseudorotaxanes as supramolecular switches, blocking the pore orifices and preventing the undesirable leakage of cargoes. When solution pH was adjusted to alkaline range, CB[7] macrocycles, acting as caps, disassociated from PBAEK stalks and opened the switches due to the dramatic decrease of ion-dipole interactions. While under acidic conditions, PBAEK stalks were broken on account of the cleavage of ketal groups, resulting in the collapse of supramolecular switches and subsequent release of encapsulated cargoes. MHzNs owning dual pH-mediated controlled release characteristic are expected to apply in many fields. In this work, the feasibility of doxorubicin (DOX)-loaded MHzNs as targeted drug delivery systems was evaluated. In vitro cellular studies demonstrate that DOX-loaded MHzNs can be easily taken up by SMMC-7721 cells, can rapidly release DOX intracellularly, and can enhance cytotoxicity against tumor cells, proving their potential for chemotherapy.