Correction: High-throughput computational screening of hypothetical metal-organic frameworks with open copper sites for CO2/H2 separation.

Correction for 'High-throughput computational screening of hypothetical metal-organic frameworks with open copper sites for CO2/H2 separation' by Mengmeng Li et al., Phys. Chem. Chem. Phys., 2022, 24, 18764-18776, https://doi.org/10.1039/D2CP01139E.

High-throughput computational screening of hypothetical metal-organic frameworks with open copper sites for CO2/H2 separation.

It is challenging to identify the optimal metal-organic framework (MOF) adsorbents for gas adsorption and membrane-based separation from the large-scale material databases. The high-throughput computational screening (HTCS) method was adopted to discover the optimal materials for CO2/H2 separation from thousands of MOFs. First, a hierarchical strategy was used to select 1092 MOFs from 13 512 MOFs, and their adsorption capacity towards the equimolar CO2/H2 mixture at 298 K and 10 bar was further calculated using the grand canonical Monte Carlo (GCMC) simulations. The results show that those MOFs with lvtb topology and organic linker 1,2,4,5-tetrazine are conducive to exhibiting high performance CO2/H2 adsorption separation among top-100 MOFs with high performance. The MOFs with pore limited diameter (PLD), largest cavity diameter (LCD), gravimetrical surface area (GSA), and void fraction in the range of 4-12 Å, 5-12 Å, 5500-6500 m2 g-1 and 0.80-0.85, respectively, have high adsorption capacity towards CO2. Second, the dynamic adsorption properties of the top-4 MOFs were simulated by the breakthrough curves of the binary (CO2/H2) and quinary (CO2/H2/CH4/CO/N2) mixtures in the fixed adsorption bed. MOF-4641 exhibits a high breakthrough time of 130 for the quinary mixture. Finally, the adsorption mechanism of CO2 in the top-4 MOFs was investigated by the radial distribution function (RDF), the mass center probability density distribution, etc. The atomic insights from HTCS and breakthrough curve predictions in this work will be helpful in developing novel porous materials and obtaining superior CO2 separation performance.

Developing Acid-Responsive Glyco-Nanoplatform Based Vaccines for Enhanced Cytotoxic T-lymphocyte Responses Against Cancer and SARS-CoV-2.

Cytotoxic T-lymphocytes (CTLs) are central for eliciting protective immunity against malignancies and infectious diseases. Here, for the first time, partially oxidized acetalated dextran nanoparticles (Ox-AcDEX NPs) with an average diameter of 100 nm are fabricated as a general platform for vaccine delivery. To develop effective anticancer vaccines, Ox-AcDEX NPs are conjugated with a representative CTL peptide epitope (CTLp) from human mucin-1 (MUC1) with the sequence of TSAPDTRPAP (referred to as Mp1) and an immune-enhancing adjuvant R837 (referred to as R) via imine bond formation affording AcDEX-(imine)-Mp1-R NPs. Administration of AcDEX-(imine)-Mp1-R NPs results in robust and long-lasting anti-MUC1 CTL immune responses, which provides mice with superior protection from the tumor. To verify its universality, this nanoplatform is also exploited to deliver epitopes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to prevent coronavirus disease 2019 (COVID-19). By conjugating Ox-AcDEX NPs with the potential CTL epitope of SARS-CoV-2 (referred to as Sp) and R837, AcDEX-(imine)-Sp-R NPs are fabricated for anti-SARS-CoV-2 vaccine candidates. Several epitopes potentially contributing to the induction of potent and protective anti-SARS-CoV-2 CTL responses are examined and discussed. Collectively, these findings shed light on the universal use of Ox-AcDEX NPs to deliver both tumor-associated and virus-associated epitopes.

Synthesis and immunological evaluation of the unnatural ß-linked mucin-1 Thomsen-Friedenreich conjugate.

MUC1 glycopeptides are attractive antigens for anti-cancer vaccine development. One potential drawback in using the native MUC1 glycopeptide for vaccine design is the instability of the O-glycosyl linkage between the glycan and the peptide backbone to glycosidase. To overcome this challenge, a MUC1 glycopeptide mimic has been synthesized with the galactose-galactosamine disaccharide linked with threonine (Thomsen-Friedenreich or Tf antigen) through an unnatural ß-glycosyl bond. The resulting MUC1-ß-Tf had a much-enhanced stability toward a glycosidase capable of cleaving the glycan from the corresponding MUC1 glycopeptide with the natural α-Tf linkage. The MUC1-ß-Tf was subsequently conjugated with a powerful carrier bacteriophage Qß. The conjugate induced high levels of IgG antibodies in clinically relevant human MUC1 transgenic mice, which cross-recognized not only the natural MUC1-α-Tf glycopeptide but also MUC1 expressing tumor cells, supporting the notion that a simple switch of the stereochemistry of the glycan/peptide linkage can be a strategy for anti-cancer vaccine epitope design for glycopeptides.

Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development.

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qß. Mouse immunization with the Qß-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qß-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

High-throughput computational screening of metal-organic frameworks with topological diversity for hexane isomer separations.

The adsorption separation of C6-C8 hydrocarbons in metal-organic frameworks (MOFs) has attracted extensive attention worldwide due to its technical feasibility and high energy efficiency in the petroleum industry. In this study, a large-scale computational screening of 13 512 MOFs with topological diversity was carried out to search optimal candidates for the simultaneous separation of two dimethyl butanes (DMB) from the quinary equimolar mixture of hexane isomers. We first screened out 841 MOFs according to their geometrical properties such as pore limited diameter (PLD) and volumetric surface area. Subsequently, high-performing MOFs were ranked out by an evaluation metric of adsorption performance score (APS), that is the product of the adsorption capacity of DMB and the selectivity of DMB over normal and mono-branched hexane isomers (N + M), on the basis of the predicted capacities by the grand canonical Monte Carlo (GCMC) simulations at 10 bar and 433 K. The structure-property relationships were established between APS and MOF descriptors such as density, PLD, etc. Among the screened 841 MOFs, the MOF with highest APS was MOF-163 because it provided an ideal pore topology with the 6.85 Å annular channel to distinguish DMB from the N + M isomers. The breakthrough predictions further demonstrated that the dimensionless residence time of 2,2-dimethylbutane (22DMB) was significantly different from that of n-hexane; this indicated that MOF-163 was a superior candidate for the dynamic separation of hexane isomers. Radial distribution function, adsorption equilibrium configurations and mass center probability density distributions were investigated to elucidate why MOF-163 could differentiate DBM from the N + M isomers. The molecular-level insights proposed in this study will facilitate the development of new MOFs for the separation of hydrocarbons in the petroleum industry.

Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice.

Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUC1 antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qß carrier with MUC1 glycopeptides containing 20-22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qß-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qß-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.

Computational design of tetrazolate-based metal-organic frameworks for CH4 storage.

CH4 is considered as an environmentally benign fuel and there is considerable interest in the development of new materials for CH4 storage. In this study, 424 tetrazolate-based metal-organic frameworks (MOFs) were computationally designed including 304 structures with the, urr and fcu topological nets and 120 structures with diverse nets. The CH4 deliverable volumetric capacities of all designed nanoporous materials and the adsorption isotherms of the top 10 hypothetical MOFs with high volumetric deliverable capacity at 298 K were predicted using molecular simulations. From the simulation results, tetrazolate blocks adjacent to pyrene or dibenzene linkers in fcu topological MOFs were found to provide lower density CH4 storage at delivery pressure (5.8 bar) as well as more efficient CH4 packing at charge pressure (65 or 35 bar), resulting in an obvious enhancement in CH4 deliverable volumetric capacity. The predicted CH4 deliverable capacity of Zr-fcu-MOF-2Py between 65 and 5.8 bar can reach 177 cm3 (STP) cm-3, the highest among tetrazolate-based MOFs studied. In comparison with NU-Py-fcu (with carboxylate blocks and pyrene linkers), its deliverable capacity increases 45.1% from 122 to 177 cm3 (STP) cm-3 under the same conditions. The enhancement mechanism from microscopic insights provided details on how the incorporation of tetrazolate links into MOFs would affect CH4 adsorption and delivery. This will lead to a novel way to enhance CH4 volumetric delivery capacity through finely tuning the chemical environment of MOFs with the incorporation of polar functional groups such as tetrazolate blocks.

Effect of an acetylene bond on hydrogen adsorption in diamond-like carbon allotropes: from first principles to atomic simulation.

By inserting an acetylene bond into the organic linkers of porous materials, hydrogen storage can be significantly enhanced; however, the mechanism of this enhancement remains elusive. Herein, we developed a new diamond-like carbon allotrope (referred as diamond-like diacetylene a.k.a. DDA) with medium pores constructed by inserting -C[triple bond, length as m-dash]C-C[triple bond, length as m-dash]C- ligands into the -C-C- bonds of diamond. The structural, mechanical, and electrical properties, as well as hydrogen storage capacities were investigated for this novel material using density functional theory and Monte Carlo simulations. The optimized geometry of DDA shows a high surface area and free pore volume of ca. 5498.76 m2 g-1 and 2.0486 m3 g-1, respectively. DDA also exhibits structural stability and special electronic properties. Interestingly, DDA exhibits exceptional gravimetric hydrogen storage capacity as well as volumetric one. The excess gravimetric and volumetric H2 uptakes at 77 K and 2.0 MPa hit a maximum of 14.12 wt% and 603.35 cm3 (STP) cm-3, respectively, which substantially exceeds those previously reported for MOF or PAF materials. Even at 243 K and 12 MPa, the total gravimetric H2 uptake of DDA reaches 5.38 wt%. To the best of our knowledge, DDA is one of porous materials with the maximum physical hydrogen uptake. It is also one of the few materials that can be close to meeting hydrogen storage target of the US department of energy at room temperature. Significantly, DDA shows the deliverable hydrogen storage capacity up to 5.28 wt% at room temperature. Through analyzing the effect of the acetylene position in the DLCAs on their hydrogen storage capacities, we found that the high hydrogen adsorption performance of DDA is mainly attributed to its high surface area, large number of adsorption sites, and appropriate binding energy. In summary, the newly developed DDA is a promising candidate for hydrogen storage and provides a new possibility for synthesizing high-performance adsorbents.

Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore.

Inflammation causes significant morbidity and mortality, necessitating effective in vivo imaging of inflammation. Prior approaches often rely on combination of optical agents with entities specific for proteinaceous biomarkers overexpressed in inflammatory tissues. We herein report a fundamentally new approach to image inflammation by targeting lysosomes undergoing acidification in inflammatory cells with a sialic acid (Sia) conjugated near-infrared profluorophore (pNIR). Sia-pNIR contains a sialic acid domain for in vivo targeting of inflamed tissues and a pNIR domain which isomerizes into fluorescent and optoacoustic species in acidic lysosomes. Sia-pNIR displays high inflammation-to-healthy tissue signal contrasts in mice treated with Escherichia coli, Staphylococcus aureus, or lipopolysaccharide. In addition, inflammation-associated fluorescence is switched off upon antibiotics treatment in mice. This report shows the potentials of Sia-pNIR for activatable dual-modality inflammation imaging, and particularly the use of lysosomes of inflamed cells as a previously unappreciated biomarker for inflammation imaging.

A near-infrared fluorescence dye for sensitive detection of hydrogen sulfide in serum.

Cy-Cl, a cationic near-infrared cyanine dye, readily reacts with hydrogen sulfide (H2S) via nucleophilic thiolation to give dose-dependent 'turn-off' fluorescence and colorimetric read-out, allowing selective detection of low levels of H2S in serum and imaging of mitochondrial H2S in living cells.

Development of NHAcGD2/NHAcGD3 conjugates of bacteriophage MX1 virus-like particles as anticancer vaccines.

The successful development of an anticancer vaccine will be a giant leap forward in cancer prevention and treatment. Herein, the bacteriophage MX1 coat protein virus-like particles (MX1 VLPs) have been conjugated with 9NHAc-GD2 (NHAcGD2) to obtain a MX1-NHAcGD2 conjugate. Intriguingly, vaccinating against this conjugate produced a robust anti-NHAcGD2 IgG response in mice, with an average IgG titer of over 3 million. More interestingly, antibodies induced by the MX1-NHAcGD2 conjugate bound well to IMR-32 neuroblastoma cells and had potent complement-dependent cytotoxic (CDC) effects on IMR-32 cells. Inspired by the superiority of the 9NHAc-GD2 antigen, we also designed another 9NHAc-modified ganglioside antigen, 9NHAc-GD3 (NHAcGD3), to overcome the hydrolytic instability of 9-O-acetylated-GD3. By coupling NHAcGD3 with MX1 VLP, the MX1-NHAcGD3 conjugate was constructed. Strikingly, vaccination of MX1-NHAcGD3 elicited high anti-NHAcGD3 IgG antibodies, which effectively recognized human malignant melanoma SK-MEL-28 cells and had a significant CDC effect against this cell line. This study provides novel MX1-NHAcGD2 and MX1-NHAcGD3 conjugates with broad clinical translational prospects as promising anticancer vaccines.

Inducing Long Lasting B Cell and T Cell Immunity Against Multiple Variants of SARS-CoV-2 Through Mutant Bacteriophage Qß-Receptor Binding Domain Conjugate.

More than 3 years into the global pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant threat to public health. Immunities acquired from infection or current vaccines fail to provide long term protection against subsequent infections, mainly due to their fast-waning nature and the emergence of variants of concerns (VOCs) such as Omicron. To overcome these limitations, SARS-CoV-2 Spike protein receptor binding domain (RBD)-based epitopes are investigated as conjugates with a powerful carrier, the mutant bacteriophage Qß (mQß). The epitope design is critical to eliciting potent antibody responses with the full length RBD being superior to peptide and glycopeptide antigens. The full length RBD conjugated with mQß activates both humoral and cellular immune systems in vivo, inducing broad spectrum, persistent, and comprehensive immune responses effective against multiple VOCs including Delta and Omicron variants, rendering it a promising vaccine candidate.

Benzothiazoline based chemodosimeters for fluorogenic detection of hypochlorous acid.

Two nonfluorescent and colorless chemodosimeters featuring benzothiazoline moiety were developed for chromo-fluorogenic detection of HOCl.

Development of a novel sialic acid-conjugated camptothecin prodrug for enhanced cancer chemotherapy.

Camptothecin (CPT) is an attractive natural drug for cancer chemotherapy. However, the poor water solubility, non-targeting feature, and adverse side effects of CPT are significant obstacles to developing an effective anticancer drug. Here, for the first time, 9-thiol-sialic acid (9-SH-Sia) is coupled to CPT by forming a disulfide releasable carbonate linkage, resulting in a novel CPT prodrug (CPT-ss-Sia) that self-assembles into nanostructures in an aqueous solution. Strikingly, CPT-ss-Sia exhibited excellent in vitro properties, including enhanced water solubility, glutathione (GSH)-triggered CPT release, and increased E-lactone ring stability. Furthermore, CPT-ss-Sia had good cancer cell-killing ability comparable to CPT. Intravenous administration of CPT-ss-Sia significantly inhibited the growth of multiple types of tumors. Histological analysis showed that CPT-ss-Sia treatment significantly reduced lesions in tumor-bearing mice compared to CPT treatment. Notably, CPT-ss-Sia treatment did not adversely affect the body weight of the mice. This is the first report of the 9-SH-Sia conjugate-based prodrug. Overall, CPT-ss-Sia has broad clinical application prospects.

Development of superior nanotheranostic agents with indocyanine green-conjugated poly(styrene-alt-maleic acid) nanoparticles for tumor imaging and phototherapy.

Developing safe, high-quality theranostic agents for cancer treatment is of great clinical value. In this work, for the first time, the clinical indocyanine green (ICG) is coupled with the biocompatible poly(styrene-alt-maleic anhydride) (PSMAn) to obtain the PSMAn-ICG polymer. The self-assembly of its hydrolyzed product in water results in ICG-conjugated poly(styrene-alt-maleic acid) nanoparticles (PSMA-ICG NPs). Intriguingly, the NPs have many advantages, including good solubility and stability in aqueous solutions, high photostability and decreased hemolytic damage to red blood cells, highlighting the importance of PSMA coupling. More interestingly, PSMA-ICG NPs significantly promote tumor targeting and enable long-term imaging of tumors. Furthermore, the administration of PSMA-ICG NPs in combination with near-infrared laser irradiation provides superior potency in the photothermal therapy of tumors. Furthermore, 9-amino-sialic acid (Sia)-coated PSMA-ICG NPs are fabricated, further enhancing tumor imaging and phototherapy. This is the first report of PSMA-NIR conjugates achieving tumor reduction in mice. Overall, this study provides novel phototheranostic agents with broad clinical transformation prospects.

Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles.

Major diseases, such as cancer and COVID-19, are frightening global health problems, and sustained action is necessary to develop vaccines. Here, for the first time, ethoxy acetalated dextran nanoparticles (Ace-Dex-NPs) are functionalized with 9-N-(4H-thieno[3,2-c]chromene-2-carbamoyl)-Siaα2-3Galß1-4GlcNAc (TCC Sia-LacNAc) targeting macrophages as a universal vaccine design platform. First, azide-containing oxidized Ace-Dex-NPs are synthesized. After the NPs are conjugated with ovalbumin (OVA) and resiquimod (Rd), they are coupled to TCC Sia-LacNAc-DBCO to produce TCC Sia-Ace-Dex-OVA-Rd, which induce a potent, long-lasting OVA-specific cytotoxic T-lymphocyte (CTL) response and high anti-OVA IgG, providing mice with superior protection against tumors. Next, this strategy is exploited to develop vaccines against infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target for neutralizing antibodies. The TCC Sia-Ace-Dex platform is preferentially used for designing an RBD-based vaccine. Strikingly, the synthetic TCC Sia-Ace-Dex-RBD-Rd elicited potent RBD-neutralizing antibodies against live SARS-CoV-2 infected Vero E6 cells. To develop a universal SARS-CoV-2 vaccine, the TCC Sia-Ace-Dex-N-Rd vaccine carrying SARS-CoV-2 nucleocapsid protein (N) is also prepared, which is highly conserved among SARS-CoV-2 and its variants of concern (VOCs), including Omicron (BA.1 to BA.5); this vaccine can trigger strong N-specific CTL responses against target cells infected with SARS-CoV-2 and its VOCs.

A rhodamine-deoxylactam based sensor for chromo-fluorogenic detection of nerve agent simulant.

N-(rhodamine B)-deoxylactam-5-amino-1-pentanol (dRB-APOH) was designed and prepared as the chromo-fluorogenic sensor for detection of a nerve agent simulant via analyte triggered tandem phosphorylation and opening of the intramolecular deoxylactam. The successful detection of diethyl chlorophosphate suggests the utility of rhodamine-deoxylactams as the chromo-fluorogenic signal reporting platform for design of sensors targeting reactive chemical species via various chemistries.

Synthesis of sialic acid conjugates of the clinical near-infrared dye as next-generation theranostics for cancer phototherapy.

Cancer is a multifaceted global health problem that requires continuous action to develop next-generation cancer theranostics. Inspired by the emerging use of indocyanine green (ICG), the only clinically approved near-infrared (NIR) dye for cancer phototherapy, here we synthesized two ICG conjugate theranostics by coupling ICG to sialic acid (Sia) through the C2 and C9 positions of Sia, respectively, referred to as Sia-C2-ICG and Sia-C9-ICG. Encouragingly, Sia-C2/C9-ICGs show superior in vitro properties, including enhanced stability, reduced non-specific binding to serum proteins, and improved blood compatibility, highlighting the benefits of Sia coupling. Notably, in vivo NIR imaging shows that Sia-C9-ICG significantly promotes tumor targeting and effectively prolongs the circulation time in the body, while Sia-C2-ICG is superior to ICG but inferior to Sia-C9-ICG in targeting tumors. Furthermore, Sia-C9-ICG combined with NIR laser irradiation can lead to excellent photothermal and photodynamic therapies for cancer cells, resulting in superior solid tumor ablation. To our knowledge, this is the first report of Sia-NIR conjugates achieving significant tumor reduction in vivo. Together, these advances render Sia-C9-ICG an attractive lead as next-generation cancer theranostics that can be translated clinically to treat human patients.

Structure Guided Design of Bacteriophage Qß Mutants as Next Generation Carriers for Conjugate Vaccines.

Vaccines are critical tools to treat and prevent diseases. For an effective conjugate vaccine, the carrier is crucial, but few carriers are available for clinical applications. In addition, a drawback of current protein carriers is that high levels of antibodies against the carrier are induced by the conjugate vaccine, which are known to interfere with the immune responses against the target antigen. To overcome these challenges, we obtained the near atomic resolution crystal structure of an emerging protein carrier, i.e., the bacteriophage Qß virus like particle. On the basis of the detailed structural information, novel mutants of bacteriophage Qß (mQß) have been designed, which upon conjugation with tumor associated carbohydrate antigens (TACAs), a class of important tumor antigens, elicited powerful anti-TACA IgG responses and yet produced lower levels of anticarrier antibodies as compared to those from the wild type Qß-TACA conjugates. In a therapeutic model against an aggressive breast cancer in mice, 100% unimmunized mice succumbed to tumors in just 12 days even with chemotherapy. In contrast, 80% of mice immunized with the mQß-TACA conjugate were completely free from tumors. Besides TACAs, to aid in the development of vaccines to protect against COVID-19, the mQß based conjugate vaccine has been shown to induce high levels of IgG antibodies against peptide antigens from the SARS-CoV-2 virus, demonstrating its generality. Thus, mQß is a promising next-generation carrier platform for conjugate vaccines, and structure-based rational design is a powerful strategy to develop new vaccine carriers.