Squaric Acid Research Articles

Proposal of spin crossover as a reversible switch of catalytic activity for the oxygen evolution reaction in two dimensional metal-organic frameworks.

The development of oxygen evolution reaction (OER) catalysts with high activity and controllability is crucial for clean energy conversion and storage but remains a challenge. Here, based on first-principles calculations, we propose to utilize spin crossover (SCO) in two-dimensional (2D) metal-organic frameworks (MOFs) to achieve reversible control of OER catalytic activity. The theoretical design of a 2D square lattice MOF with Co as nodes and tetrakis-substituted cyanimino squaric acid (TCSA) as ligands, which transforms between the high spin (HS) and the low spin (LS) state by applying an external strain (∼2%), confirms our proposal. In particular, the HS-LS spin state transition of Co(TCSA) considerably regulates the adsorption strength of the key intermediate HO* in the OER process, resulting in a significant reduction of the overpotential from 0.62 V in the HS state to 0.32 V in the LS state, thus realizing a reversible switch for the activity of the OER. Moreover, the high activity of the LS state is confirmed by microkinetic and constant potential method simulations.

Janus Kinase Inhibitors in the Treatment of Alopecia Areata.

Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair loss, which can have huge psychosocial impact for those affected. Treatment modalities which have been used so far included nonspecific immunosuppressive medications, such as corticosteroids, cyclosporine, and methotrexate, or topical immunomodulators, such as diphencyprone, dithranol, and squaric acid dibutylester. The recognition of the importance of Janus kinase pathway in alopecia areata pathogenesis enabled more specific approaches in treatment. Positive outcomes of Janus kinase inhibitors in several trials granted approval for baricitinib which became the first on-label treatment for alopecia areata. The aim of this review is to summarize the role, efficacy and safety of several Janus kinase inhibitors in alopecia areata.

Facile Synthesis of Pyrrolyl-Containing Semisquaraines in Water as Precursors for Non-Symmetric Squaraines

One-step reactions between squaric acid and pyrroles, such as 3-ethyl-2,4-dimethyl-pyrrole and 1,2,5-trimethylpyrrole, in water provide the corresponding pyrrol-2-yl- and pyrrol-3-yl-containing semisquaraines in high yields. These semisquaraines serve as useful precursors for the synthesis of various non-symmetric pyrrole-containing squaraine dyes.

Spotlight in Plastic Surgery: January 2023.

Spotlight in Plastic Surgery: January 2023.

8-Aminoquinoline-containing squaric acid congeners as polarity and viscosity probes

Squaraine-type dyes are privileged motifs and scaffolds with valuable and tunable photophysical properties, and have found numerous applications in various areas of chemical and biological sciences. Yet, environment-sensing capabilities of squaraine dyes have not been widely explored. This study illustrates how selective incorporation of a readily available 8-aminoquinoline moiety onto squaric acid or squarate scaffolds fine-tunes environment-sensing capabilities of these dyes. The squaraine motif is required for achieving meaningful correlations between probe’s photophysical properties and media’s properties, whereas semi-squaraine and squaramide analogues exhibit inferior environment-sensing capabilities. The 1,3-bis(8-aminoquinolinyl)squaraine dye shows potential as a multiplexing environment-sensitive probe that could sense media’s polarity variations via absorption changes, and environmental viscosity via amplitude-weighted fluorescence lifetime changes.

Preparation of an Antioxidant Assembly Based on a Copolymacrolactone Structure and Erythritol following an Eco-Friendly Strategy.

The study presents the achievement of a new assembly with antioxidant behaviour based on a copolymacrolactone structure that encapsulates erythritol (Eryt). Poly(ethylene brassylate-co-squaric acid) (PEBSA) was synthesised in environmentally friendly conditions, respectively, through a process in suspension in water by opening the cycle of ethylene brassylate macrolactone, followed by condensation with squaric acid. The compound synthesised in suspension was characterised by comparison with the polymer obtained by polymerisation in solution. The investigations revealed that, with the exception of the molecular masses, the compounds generated by the two synthetic procedures present similar properties, including good thermal stability, with a Tpeak of 456 °C, and the capacity for network formation. In addition, the investigation by dynamic light scattering techniques evidenced a mean diameter for PEBSA particles of around 596 nm and a zeta potential of -25 mV, which attests to their stability. The bio-based copolymacrolactone was used as a matrix for erythritol encapsulation. The new PEBSA-Eryt compound presented an increased sorption/desorption process, compared with the PEBSA matrix, and a crystalline morphology confirmed by X-ray diffraction analysis. The bioactive compound was also characterised in terms of its biocompatibility and antioxidant behaviour.

Erratum to: NIR-II light-activated two-photon squaric acid dye with type I photodynamics for antitumor therapy

Article Erratum to: NIR-II light-activated two-photon squaric acid dye with type I photodynamics for antitumor therapy was published on December 1, 2022 in the journal Nanophotonics (volume 11, issue 21).

Theoretical Validation of In Chemico Skin Sensitization Assay "ADRA" Using the Products Formed by Nucleophilic Reagents and Chemicals.

Amino acid derivative reactivity assay (ADRA) is an in chemico assay for assessing the skin sensitization potential of chemicals by evaluating the reactivity of nucleophilic reagents that mimic skin proteins. N-(2-(1-Naphthyl)acetyl)-l-cysteine (NAC) and α-N-(2-(1-naphthyl)acetyl)-l-lysine (NAL), used as nucleophilic reagents, are small-molecule derivatives of two different amino acids, each with a naphthalene ring attached. The rate of decrease in the amount of NAC or NAL in the reaction solution is evaluated in this assay as an indicator of the test substance's skin sensitization ability. However, the products formed between the nucleophilic reagent and the test substance, which play an important role in vivo, are not directly identified. Therefore, six highly reactive chemicals, including the proficiency substances listed in the OECD Test Guidelines─squaric acid diethyl ester, 2-methyl-2H-isothiazol-3-one (MI), p-benzoquinone, palmitoyl chloride, diphenylcyclopropenone (DPCP), and imidazolidinyl urea (IU)─were used to determine each formed product. Samples were prepared according to the standard ADRA method, and the formed products were predicted on the basis of the reaction mechanism. Excluding DPCP, the estimated structures were validated using mass spectrometry and nuclear magnetic resonance spectrometry on the synthesized samples. In this manner, the products of each nucleophile were confirmed for all examined test substances. The estimated structure products were obtained through a series of reactions initiated by the nucleophilic attack of NAC's thiol group or NAL's amino group on the test substance's electron-deficient carbonyl carbon. However, contrary to expectations, disulfide-linked-type ring-opened products were detected in the case of MI, and products with free formaldehyde in solution were detected in the case of IU. In summary, all skin sensitizers tested herein reacted with NAC and/or NAL to give products. This supports the theoretical validity of ADRA, which provides an indirect evaluation of the formed products based on a decrease in nucleophilic reagents.

NIR-II light-activated two-photon squaric acid dye with Type I photodynamics for antitumor therapy

Abstract Photodynamic therapy (PDT) for hypoxic tumors has attracted wide attention owing to its noninvasiveness, easy maneuverability, and instantaneity. However, hypoxia in tumors and penetration depth of conventional ultraviolet light has greatly weakened its performance. To solve these problems, under NIR-II light irradiation, squaric acid nanoparticles (SQ NPs) with superior reactive oxygen, especially, hydroxyl radicals (•OH) production performance were first utilized for hypoxic tumor therapy. SQ NPs with intense light capture capability, intense NIR emission, and excellent photobleaching resistance show continuous •OH generation capabilities under NIR-II laser excitation. Through the superior PDT performance, the growth of hypoxic tumors was effectively inhibited, and the survival rate of mice was improved. This work highlights the application of NIR-II photoexcitation in deep tissue type I photodynamic therapy of hypoxic tumors, which will facilitate the development of hypoxic tumor PDT in deep depth.

Squaric acid driven supramolecular metallogels of Cd(II) and Zn(II): Sensitive inhibitors for multi-drug resistance ESKAPE pathogens

The article depicts the synthesis and significance of two metallogels of squaric acid implementing Cd(II) and Zn(II)-metal salts. N,N΄-dimethyl formamide has been utilised as an immobilised solvent for successive construction of metal ions directed both gel scaffolds. These metallogels exhibit an intriguing visco-elasticity which gets experimentally validated by rheological findings. Microstructural versatility with varied metal ions and EDS elemental analysis confirm the presence of all the gel-forming constituents present in the observed hierarchical morphological visualizations for both soft-scaffolds. FT-IR data indicate the considerable shifting of peaks compared to precursor gel-forming ingredients and also establish that the metallogel-development tactic might be progressed by non-covalent type supramolecular interactions. Comparative analysis of these metallogels as anti-bacterial agents against multi-drug resistive deadly pathogens including Gram-negative bacteria Escherichia coli, Salmonella typhimurium, Vibrio parahaemolyticus and Gram-positive bacteria Bacillus cereus, and Staphylococcus aureus reveals them as the potential and promising bio-functional stuffs. Thus, the bactericidal effects of Cd(II) and Zn(II) based squaric acid mediated metallogels against ESKAPE pathogens are accounted in this study.

Use of Contact Immunotherapy in the Treatment of Skin Diseases Other than Alopecia Areata.

For decades, contact immunotherapy with dinitrochlorobenzene, diphencyprone, and squaric acid dibutylester has played an important role in both clinical practice and scientific research. It is listed as the first-line treatment for extensive alopecia areata and was more recently approved for melanoma treatment as an orphan drug in the USA. Moreover, owing to the relative low cost and safety, topical immunotherapy has also been used in many infectious, neoplastic, and inflammatory dermatological diseases. It is especially valuable in vulnerable groups, for cosmetic/pain sensitive areas, or for multiple lesions. In this review, we summarize the current evidence supporting the use of contact immunotherapy for treatment of skin diseases, from articles collected from PubMed database. Owing to space limitation and already numerous studies focusing on alopecia areata, we include only skin diseases other than alopecia areata. In addition to diseases that have been reported to be treated by contact immunotherapy, the hypothesized mechanism, prognosis prediction, efficacy, and safety of these topical agents are discussed.

Synthesis and fluorescence of N-squaraine dianions derived from electron-deficient primary anilines

Squaraines are 1,3-disubstituted squaric acid derivatives featuring intense fluorescence in the visible. Unlike their parent compounds, N-squaraines obtained by condensation reaction between squaric acid and primary anilines are non-fluorescent compounds. The incorporation of electron-withdrawing substituents in the para position of the phenyl rings turns these compounds acidic enough to form the corresponding dianions by acid-base reaction with alkaline hydroxide in mixed DMSO-H2O solvent mixtures. This work reports the microwave-assisted synthesis of N-squaraines and the investigation of the optical characteristics of their dianions. The dianionic squaraines have a C4N2O22− squaryl core with absorption maxima at 450–748 nm (molar absorptions up to 7.6 × 104 M−1 cm−1). The N-squaraine dianions are highly fluorescent in the 507–644 nm range (quantum yields 0.18–0.72). Due to their negative charge, and contrary to the expectations, anionic N-squaraines are chemically stable for hours in 50% v/v H2O–DMSO solvent mixtures. DFT calculations show the absorption bands are S0 → S1 excitations (HOMO → LUMO) and S1 → S0 transitions (LUMO → HOMO) for the emission. In both cases, the calculated wavelengths compare well with the experimental observations.

Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins.

ABSTRACTThe clonal bacterial species Acinetobacter baumannii is an emerging multidrug-resistant pathogen which causes high-lethality infections. Cells of A. baumannii are surrounded by the type-specific capsular polysaccharide (CPS), which provides resistance to the protective mechanisms of the host and is considered a target for immunization. The conjugates of three inert carrier proteins and A. baumannii type K9 CPS fragments, which contained various numbers of oligosaccharide repeats (K-units), were synthesized by periodate oxidation and squaric acid chemistry. The conjugates were applied to immunize mice, and chemical synthesis by squaric acid was shown to significantly improve the immunogenic properties of glycoconjugate. In BALB/c mice, IgG antibodies were predominant among type K9 CPS reactive antibodies, and their total content was several times higher than that of IgM. Immune sera were characterized by their opsonization ability during practically the entire lives of the experimental mice. The sera were cross-reactive, but the highest specificity was observed against the antigen (type K9 CPS) used for immunization. The immunization of BALB/c and ICR-1 mice with a glycoconjugate without adjuvants led to varying degrees of stimulation of IL-10, IL-17A, and TNF-α production, but not IL-4 production in the ICR-1 mice. This is in contrast to the BALB/c mice, in which γ-IFN production was also activated. The protective effectiveness of the glycoconjugates obtained by squaric acid chemistry was demonstrated by experiments that involved challenging immunized and nonimmunized animals with a lethal dose of A. baumannii K9.IMPORTANCE Immunization by glycoconjugates with A. baumannii type K9 CPS fragments induced a high level of antibodies (predominantly IgG) in sera, which reacted specifically with the CPS of A. baumannii type K9, as well as a long immunological memory. The sera of immunized animals efficiently opsonized A. baumannii type K9. Immunization resulted in the balanced production of pro/anti-inflammatory lymphokines and protective antibodies to ensure the survival of the mice infected with A. baumannii. The level of specific antibodies was sufficient to provide protective immunity against the challenge by A. baumannii, making this approach applicable in the development of vaccine preparations.

From Automated Synthesis to In Vivo Application in Multiple Types of Cancer-Clinical Results with [68Ga]Ga-DATA5m.SA.FAPi.

Radiolabeled FAPI (fibroblast activation protein inhibitors) recently gained attention as widely applicable imaging and potential therapeutic compounds targeting CAF (cancer-associated fibroblasts) or DAF (disease-associated fibroblasts in benign disorders). Moreover, the use of FAPI has distinct advantages compared to FDG (e.g., increased sensitivity in regions with high glucose metabolism, no need for fasting, and rapid imaging). In this study, we wanted to evaluate the radiochemical synthesis and the clinical properties of the new CAF-targeting tracer [68Ga]Ga-DATA5m.SA.FAPi. The compound consists of a (radio)chemically easy to use hybrid chelate DATA.SA, which can be labeled at low temperatures, making it an interesting molecule for ‘instant kit-type’ labeling, and a squaric acid moiety that provides distinct advantages for synthesis and radiolabeling. Our work demonstrates that automatic synthesis of the FAP inhibitor [68Ga]Ga-DATA5m.SA.FAPi is feasible and reproducible, providing convenient access to this new hybrid chelator-based tracer. Our studies demonstrated the diagnostic usability of [68Ga]Ga-DATA5m.SA.FAPi for the unambiguous detection of cancer-associated fibroblasts of various carcinomas and their metastases (NSCLC, liposarcoma, parotid tumors, prostate cancer, and pancreas adenocarcinoma), while physiological uptake in brain, liver, intestine, bone, and lungs was very low.

Silver‐Mediated Squaric Acid Reduction as a Facile, Ambient‐temperature and Seedless Route to Tunable Bimetallic Au/Ag Nanostars and Nanosnowflakes

AbstractBimetallic Au/Ag nanoparticles were successfully synthesized using a facile and reproducible method involving rapid, room‐temperature mixing of aqueous solutions of HAuCl4 and AgNO3 in the presence of squaric acid as both the reducing agent and surface capping ligand. Variation in the initial Au : Ag molar ratio yielded a tunable anisotropic shape and affiliated surface plasmon resonance. The nanoparticles displayed excellent stability in water for at least 10 weeks and showed robust catalytic activity in the borohydride‐assisted reduction of the model substrate 4‐nitrophenol.

Editors' Selections from Relevant Scientific Publications

Highlights from the Literature| August 01 2022 Editors' Selections from Relevant Scientific Publications Author & Article Information Online ISSN: 1940-6215 Print ISSN: 1940-6207 ©2022 American Association for Cancer Research2022American Association for Cancer Research Cancer Prev Res (Phila) (2022) 15 (8): 473. https://doi.org/10.1158/1940-6207.CAPR-15-8-HFL Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record August 1 2022 Citation Editors' Selections from Relevant Scientific Publications. Cancer Prev Res (Phila) 1 August 2022; 15 (8): 473. https://doi.org/10.1158/1940-6207.CAPR-15-8-HFL Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Malignant melanoma (by Nephron via Wikimedia Commons) A mouse study shows that proinflammatory topical therapy can shrink giant nevi: large, pigmented areas of skin that can become cancerous. In humans, giant nevi can cover up to 80% of the body’s surface and progress to melanomas 12% of the time. Choi et al. developed a genetically modified mouse model of giant nevi that developed pigmented skin patches and melanoma. They then treated the pigmented areas with inhibitors of the signaling molecules MEK, PI3K and c-KIT, or squaric acid dibutylester (SADBE), a topical treatment that induces inflammation and recruits macrophages. These treatments cleared much of the pigmentation and SADBE treatment eliminated the risk of melanoma. SADBE was also effective at treating patches of human nevi that had been grafted onto mice, suggesting that topical therapies that induce this type of inflammation could be developed to treat children with congenital giant nevi. Choi... You do not currently have access to this content.

Synthesis and Comparative Studies of Glucose Oxidase Immobilized on Fe3O4 Magnetic Nanoparticles Using Different Coupling Agents.

Squaric acid (SA) is a compound with potential to crosslink biomacromolecules. Although SA has become over the last years a well-known crosslinking agent as a result of its good biocompatibility, glutaraldehyde (GA), a compound with proven cytotoxicity is still one of the most used crosslinkers to develop nanomaterials. In this regard, the novelty of the present study consists in determining whether it may be possible to substitute GA with a new bifunctional and biocompatible compound, such as SA, in the process of enzyme immobilization on the surface of magnetic nanoparticles (MNPs). Thus, a direct comparison between SA- and GA-functionalized magnetic nanoparticles was realized in terms of physico-chemical properties and ability to immobilize catalytic enzymes. The optimal conditions of the synthesis of the two types of GOx-immobilized MNPs were described, thus emphasizing the difference between the two reagents. Scanning Electron Microscopy and Dynamic Light Scattering were used for size, shape and colloidal stability characterization of the pristine MNPs and of those coupled with GOx. Binding of GOx to MNPs by using GA or SA was confirmed by FT-IR spectroscopy. The stability of the immobilized and free enzyme was investigated by measuring the enzymatic activity. The study confirmed that the resulting activity of the immobilized enzyme and the optimization of enzyme immobilization depended on the type of reagent used and duration of the process. The catalytic performance of immobilized enzyme was tested, revealing that the long-term colloidal stability of SA-functionalized MNPs was superior to those prepared with GA. In conclusion, the SA-functionalized bioconjugates have a better potential as compared to the GA-modified nanosystems to be regarded as catalytic nanodevices for biomedical purposes such as biosensors.

New Cryogels Based on Poly(vinyl alcohol) and a Copolymacrolactone System: I-Synthesis and Characterization.

Physical cryogels were obtained using the successive freeze–thaw technique of poly(vinyl alcohol) (PVA)/poly(ethylene brassylate-co-squaric acid) (PEBSA) solutions. The cryogel systems were prepared by using two different molecular weights of PVA and PEBSA with three different ratios between the ethylene brassylate (EB) and squaric acid (SA) comonomers. The presence of interactions, the thermal properties and the morphology were investigated using Fourier Transform Infrared Spectroscopy (FT-IR), thermogravimetry (TGA and DTG) and scanning electron microscopy (SEM), respectively. The influence of the composition on the degree of swelling in a physiological environment was demonstrated. The study highlighted improvements in terms of new network flexibility due to the intermolecular chains interactions brought by the introduction of PEBSA in the cryogel structure. We also concluded that the presence of PEBSA in the PVA/PEBSA cryogel network improved the loading capacity of the new system with specific hydrophobic agents, for example essential oils, which (due to their antimicrobial character) can lead to the use of new systems obtained for various applications.

Machine-Learning-Guided Identification of Coordination Polymer Ligands for Crystallizing Separation of Cs/Sr.

Separation of Cs/Sr is one of many coordination-chemistry-centered processes in the grand scheme of spent nuclear fuel reprocessing, a critical link for a sustainable nuclear energy industry. To deploy a crystallizing Cs/Sr separation technology, we planned to systematically screen and identify candidate ligands that can efficiently and selectively bind to Sr2+ and form coordination polymers. Therefore, we mined the Cambridge Structural Database for characteristic structural information and developed a machine-learning-guided methodology for ligand evaluation. The optimized machine-learning model, correlating the molecular structures of the ligands with the predicted coordinative properties, generated a ranking list of potential compounds for Cs/Sr selective crystallization. The Sr2+ sequestration capability and selectivity over Cs+ of the promising ligands identified (squaric acid and chloranilic acid) were subsequently confirmed experimentally, with commendable performances, corroborating the artificial-intelligence-guided strategy.

Making a mouse out of a molehill: how precision modeling repurposes drugs for congenital giant nevi

Patients with congenital giant nevi (CGN), which can compromise quality of life and progress to melanoma, have limited treatment options. Choi et al. have demonstrated that topical application of a proinflammatory hapten for alopecia treatment [squaric acid dibutylester (SADBE)] caused nevus regression and prevented melanoma in an Nras mouse CGN model. Their results demonstrate the promise of repurposing drugs through precision modeling.