Properties Of Conjugates Research Articles

C2-linked alkynyl poly-ethylene glycol(PEG) adenosine conjugates as water-soluble adenosine receptor agonists.

A series of 12 novel polyethylene-glycol(PEG)-alkynyl C2-adenosine(ADN) conjugates were synthesized using a robust Sonogashira coupling protocol and characterized by NMR spectroscopy and mass spectrometry analysis. The ADN-PEG conjugates showed null to moderate toxicity in murine macrophages and 12c was active against Mycobacterium aurum growth (MIC=62.5mg/L). The conjugates were not active against Mycobacterium bovis BCG. Conjugates 10b and 11b exhibited high water solubility with solubility values of 1.22 and 1.18 mg/ml, respectively, in phosphate buffer solutions at pH6.8. Further, 10b and 11b induced a significant increase in cAMP accumulation in RAW264.7 cells comparable with that induced by adenosine. Analogues 10c, 11c and 12c were docked to the A1 , A2A , A2B and A3 adenosine receptors (ARs) using crystal-structures and homology models. ADN-PEG-conjugates bearing chains with up to five ethyleneoxy units could be well accommodated within the binding sites of A1 , A2A and A3 ARs. Docking studies showed that compound 10b and 11b were the best A2A receptor binders of the series, whereas 12c was the best binder for A1 AR. In summary, introduction of hydrophilic PEG substituents at the C2 of adenine ring significantly improved water solubility and did not affect AR binding properties of the ADN-PEG conjugates.

Time series change detection using reservoir computing networks for remote sensing data

In this study, a multivariate time series forecasting model applicable to high-dimensional short-term forecasting is proposed. The Reservoir Computing Network (RCN) state reduction method is investigated to address the dimensionality arising from high-dimensional data. To enable the states to express very distant dependencies in time so that the RCN satisfies the echo state property, a bidirectional RCN model is investigated to capture the dependencies of the data forward and backward in time. To solve the short-term data prediction, the spatiotemporal transformation theory is combined with the RCN to exploit the conjugate property between delayed and nondelayed embeddings of dynamical systems, and the correlation between variables in high-dimensional systems is used to compensate for the shortcomings of short-term series, design the method of the RCN training, and complete the prediction of future states. In the experiments, four existing models based on two different data sets were used for comparison, and the results showed that our method has better prediction performance.

Engineering gold nanoparticles for molecular diagnostics and biosensing.

Advances in nanotechnology and medical science have spurred the development of engineered nanomaterials and nanoparticles with particular focus on their applications in biomedicine. In particular, gold nanoparticles (AuNPs) have been the focus of great interest, due to their exquisite intrinsic properties, such as ease of synthesis and surface functionalization, tunable size and shape, lack of acute toxicity and favorable optical, electronic, and physicochemical features, which possess great value for application in biodetection and diagnostics purposes, including molecular sensing, photoimaging, and application under the form of portable and simple biosensors (e.g., lateral flow immunoassays that have been extensively exploited during the current COVID-19 pandemic). We shall discuss the main properties of AuNPs, their synthesis and conjugation to biorecognition moieties, and the current trends in sensing and detection in biomedicine and diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Investigation of Antiblastic and Antibacterial Properties of Binuclear Platinum (II)-Interferon Conjugate

Introduction: This work aimed to create a new platinum-interferon conjugate and investigate its properties. Background: Multiple drug resistance of tumor cells is a serious challenge in modern medicine. Neoplastic diseases are often complicated by persistent bacterial infections, which impairs efficacy and the outcome of anticancer therapy. The development of new bifunctional drugs for the treatment of tumor growth and bacterial complications is an urgent task. Objective: The objective of this study was to evaluate the complex antiblastic and antibacterial properties of interferon-platinum conjugate in vitro. Material and Methods: The coordination complex of dichloro-N,N,N,N-tetrakis-(2-aminoethyl)- 1,6-hexamethylenediaminobisplatin dichloride was used for production of conjugate with human α-interferon. The binding of a metal complex with protein was established by means of radiochemical neutron activation analysis. As test objects, we used lympholeukemic Jurkat cells line, human lymphocytes in reaction of lymphocyte blastic transformation and different strains of microorganisms, including Staphylococcus aureus and Pseudomonas aeruginosa. Results: Binuclear platinum human α-interferon conjugate has a significant dose-dependent antibacterial and antiproliferative suppressive effect on target cells and bacteria. Conclusion: The tested preparation can be of a certain interest in drug designing for rational antiblastic therapy, especially in the case of infectious complications. This conjugate can be a convenient platform for creating drugs for the complex therapy of oncological diseases with bacterial complications.

Understanding of Photo-Induced Reversible Rearrangement from Borepin to Borirane.

The first reversible photoisomerization between a borepin and a borirane was reported in the photo-induced reactions of B(npy)Ar2 (npy=2-(naphthalen-1-yl) pyridine, Ar=phenyl or electron rich aryl; S. Wang, et al. Angew. Chem. Int. Ed. 2019, 58, 6683-6687). In this work, the detailed mechanisms of the unprecedented reversible photoisomerization between the borepin (compound a) and the borirane (compound b) of B(npy)Ph2 in the first excited singlet (S1 ) state and the ground (S0 ) state were studied by carrying out calculations with the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combined with time-dependent density functional theory (TD-DFT). The calculation results show that photoexcitation of a-S0 at 365 nm and b-S0 at 450 nm populate their S1 state with evident charge transfer characteristics. The photoisomerization is triggered in the S1 state and ends in the S0 state, at which the intersection points in a (S1 /S0 )x intersection seam participate in and promote phenyl migration and ring-closure processes. Furthermore, we reveal that the not large energy difference (less than 0.6 eV) and similar conjugation properties of π electrons between a-S0 and b-S0 are responsible for their unique photo-reversible reactivity, compared with those of the isomers of the thermally reversible compound B(ppy)Mes2 . Our results contribute to an understanding of the excited-state reactivity of organoboron compounds and will be useful to support the design of new boron-based photo-responsive materials.

Delivery of Bioactive Albumin from Multi-Functional Polyampholyte Hydrogels.

Tissue engineered scaffolds are currently being explored to aid in healing and regeneration of non-union fractures in bone. Additionally, albumin has been demonstrated to provide benefits to healing when applied to injury sites. This paper focuses on delivery of calcium modified, bioactive bovine serum albumin (BSA) from a multi-functional polyampholyte polymer scaffold. First, the inherent nonfouling and conjugation properties of the polyampholyte hydrogel were verified to determine the impact of calcium exposure. The polyampholyte hydrogel delivery platform was then assessed with calcium titrations and osteoblast-like cell (MC3T3-E1) adhesion, proliferation, and viability evaluations. Finally, integrin inhibitors were used to identify the binding mechanisms that mediate cell adhesion to the calcium-modified BSA-conjugated hydrogels. An increase in cell adhesion was observed following calcium exposure up to 0.075 M, although this and higher calcium concentrations affected hydrogel stability and cell growth. BSA exposed to 0.05 M calcium and delivered from polyampholyte hydrogels promoted the most promising viable cell adhesion over 7 days. Cell adhesion to the calcium-modified BSA-conjugated hydrogels appeared to be regulated by arginine-glycine-aspartic acid (RGD) and collagen specific integrins. These results demonstrate that the delivery of calcium modified BSA from an implantable polymer scaffold is promising for bone tissue engineering applications.

Exploration of DNA processing features unravels novel properties of ICE conjugation in Gram-positive bacteria

Integrative and conjugative elements (ICEs) are important drivers of horizontal gene transfer in prokaryotes. They are responsible for antimicrobial resistance spread, a major current health concern. ICEs are initially processed by relaxases that recognize the binding site of oriT sequence and nick at a conserved nic site. The ICESt3/Tn916/ICEBs1 superfamily, which is widespread among Firmicutes, encodes uncanonical relaxases belonging to a recently identified family called MOBT. This family is related to the rolling circle replication initiators of the Rep_trans family. The nic site of these MOBT relaxases is conserved but their DNA binding site is still unknown. Here, we identified the bind site of RelSt3, the MOBT relaxase from ICESt3. Unexpectedly, we found this bind site distantly located from the nic site. We revealed that the binding of the RelSt3 N-terminal HTH domain is required for efficient nicking activity. We also deciphered the role of RelSt3 in the initial and final stages of DNA processing during conjugation. Especially, we demonstrated a strand transfer activity, and the formation of covalent DNA-relaxase intermediate for a MOBT relaxase.

Physicochemical characterization, emulsifying and antioxidant properties of the polysaccharide conjugates from Chin brick tea (Camellia sinensis)

Tea polysaccharide conjugate fractions (TPCs) with different molecular weights (TPC-40, TPC-60, and TPC-80, MW = 1355 to 204 kDa) were prepared from Chin brick tea using graded alcohol precipitation. The physiochemical and functional properties of TPCs were investigated. Results showed that TPC-80 (204 kDa) had the highest antioxidant activity attributed to its higher phenolic and theabrownin contents. Moreover, this fraction had the highest surface pressure (16.2 ± 0.9 mN/m), but the lowest interfacial dilatational modulus (30.3 ± 2.2 mN/m) than TPC-40 (1355 kDa) and TPC-60 (955 kDa). As a result, TPC-80 had the highest emulsifying activity but the lowest emulsion stabilizing properties due to its fastest adsorption kinetics but the relatively thin interfacial coating on the oil droplets. Overall, our results indicate that the chemical compositions and structural characteristics of TPCs significantly impact their functional attributes. TPCs have the potential to be a novel natural antioxidant emulsifier in food industry.

Structural, functional, and anti-cancer properties of conjugates of quinoa protein isolate and olive leaf polyphenolic extract: Application in production of bread

Plant-based proteins are of growing interest in the food industry as an alternative to replace animal based ones, however, their functional properties are limited and research is needed in order to improve emulsifying, foaming, solubility properties. The objectives of the present study were to investigate the impacts of complexation between quinoa protein isolate (QPI) and different concentrations of olive leaf polyphenolic extract (OLE) (0.1 %, 0.2 %, 0.3 %, 0.4 %, and 0.5 %) on the structural changes, functional properties, and in-vitro gastric digestion of QPI. The cytotoxicity of the hydrolyzed QPI/OLE complex, in which proteins turn to bioactive peptides, was evaluated using human stomach cancer cell lines. Additionally, bread using optimum QPI/OLE complex was produced and textural, sensorial, and color properties were evaluated. Fluorescence quenching and surface hydrophobicity measurements showed that QPI and OLE were complexed mainly through hydrophobic interactions. SDS-PAGE revealed that the complexation between the protein and phenolic compounds was appropriate and also complexes were highly digestible in stomach-like conditions. Additionally, OLE could enhance solubility, foaming as well as emulsification properties of QPI significantly. The rate of lipid hydroperoxide formation in QPI/OLE samples containing greater amounts of OLE was also reduced significantly. QPI/OLE complexes also exhibited a large potential to scavenge free radicals. In-vitro digestion experiment showed that the addition of OLE to the QPI solution promoted the production of bioactive peptides. According to the anti-cancer results, hydrolyzed QPI/OLE complexes exhibited a greater cell survival reduction in comparison to the OLE alone. Analysis of produced bread also revealed that the hardness of samples decreased with addition of QPI/OLE complexes. This study demonstrated that QPI/OLE complex shows the potential to be developed by food industry as a tailor-made functional food with health benefits. • Hydrophobic interactions were the main interaction mechanism between QPI and OLE. • Addition of OLE improved the solubility of QPI, significantly. • Complexation with OLE promoted the production of bioactive peptides during digestion. • Digested QPI/OLE complex exhibited a greater human stomach cancer cell survival reduction in comparison to the OLE alone. • Bread with QPI/OLE complexes was made without negative changes in bread’s properties.

Fabrication, Structural and Emulsifying Properties of Egg White Protein-Dextran Conjugates through Maillard Reaction

Fabrication, Structural and Emulsifying Properties of Egg White Protein-Dextran Conjugates through Maillard Reaction

Abstract 1401: Lead optimization of radiopharmaceuticals for molecular radiotherapy and preclinical evaluation

Abstract Molecular Radiotherapy (MRT) targeting SSTR2 or PSMA have proven to be highly efficient for the treatment of neuroendocrine or metastatic prostate cancer, respectively. Beyond the leading radiopharmaceutical molecules 177Lu-DOTATATE or 177Lu-PSMA-617, a variety of vectors (small molecules, peptides, panel of biologics) have been developed on the same targets in order to improve the biodistribution within the tumor, the blood clearance, the route of elimination or the dosimetry. The labeling of the targeting ligand, whatever its nature, is a crucial step as it may affect significantly the properties of the theranostic conjugate, i.e. its binding affinity, PK and biodistribution. The addition of linkers, such as albumin binding domain or PEG, and choice of chelating agents have a major impact on the chemical and biological properties of the vectors. Random or site-specific bioconjugation, click chemistry, also have to be considered in the early stage as the choice of the selected technology will modify your development plan and manufacturing. New ligands and biological platforms are now being developed based on this historical knowledge, improved Target Product Profiles are built to conduct optimal lead optimization of MRT. Herein, we will present our lead optimization and preclinical evaluation process to select efficiently good radiolabeled molecules and list the key parameters to be checked. To date, it remains hard to predict the behavior of the modified bioconjugated molecules, and versatile synthesis strategies are needed to screen various combinations of radiometal complexes, linker and conjugation function, in order to converge rapidly to the optimized bioconjugate. As an example, we will present a study case where the conjugation of various bifunctional chelating agents on a small NTS1 receptor antagonist resulted in drastically different in vivo behavior of the resulting 68Ga-labeled compounds. Once optimal in vivo tumor uptake has been achieved, preclinical evaluation requires the selection of appropriate and relevant models, driven by target expression, radioresistance, and potentially tumor immune infiltrate for combination studies with immunotherapies. The therapeutic evaluation should take into consideration the dose and specific activity, the tolerance of a model related to ionizing radiations and the scheduling of treatments (cumulated dose, fractionation). We will present our recent results which highlight the importance to optimize these parameters to improve the efficacy of MRT. Citation Format: Emma Renard, Olivier Raguin, Victor Goncalves, Celine Mothes, Mathieu Moreau, Claire Bernhard, Peggy Provent, Frederic Boschetti, Franck Denat, Fabrice Viviani, Cyril Berthet. Lead optimization of radiopharmaceuticals for molecular radiotherapy and preclinical evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1401.

Abstract 1405: Novel ADC platform delivers promising in vivo activity and safety

Abstract The physiochemical properties of an antibody-drug conjugate (ADC) are one key design attribute that can impacts its stability and pharmacokinetics/pharmacodynamics and are one of the key design attributes. Typically, ADCs with better hydrophilicity are less prone to aggregation, and have lower systemic clearance, and greater anti-tumor activities and thus a larger therapeutic index. However, the need to incorporate lipophilic payloads with an enhanced bystander effects has posed significant challenges to ADC and linker design, especially at drug-antibody ratios of 8 and even 16higher. Here we present a novel ADC platform that can greatly improveimproves the hydrophilicity, physiochemical stability, and pharmacokinetics of ADCs conjugated to lipophilic payloads such as exatecan, MMAE, SN38 and EErribulin. All payloads which are allare expect to exhibit strong bystander effects.By introducing PEG, polyhydroxyl and/or polycarboxyl groups, we generated hydrophilic linkers that enable site specific and, highly homogeneous conjugation of payloads to multiple prototypical antibodies at DAR 4, 8 and even 16. Compared. These ADCs were evaluated for their binding affinity, hydrophilicity, physiochemical stability, in vitro and in vivo anti-tumor activities, tolerability, and pharmacokinetics. In addition, comparisons were made with with theirthe corresponding naked unconjugated parent antibodies and conventional vedotin- and deruxtecan-based ADCs., these ADCs were evaluated for their binding affinity, hydrophilicity, physiochemical stability, in vitro and in vivo anti-tumor activities, tolerability, and pharmacokinetics. These novel ADCs were found to be stable at 37℃ for up to 30 days, after for at least 5 cycles of freeze-thaw, and at concentrations as high as 100 mg/mL, as assessed by visual inspection, hydrophobic interaction chromatography and size exclusion chromatography. Binding affinities of these ADCs to target-positive cell lines were similar to their corresponding naked unconjugated parent antibodies. These ADCs demonstrated strong tumor growth inhibition with single or repeated dosing in multiple tumor xenograft mouse models. The pharmacokinetic profiles of these ADCs are similar to those of the naked respective parent unconjugated antibodies. Assessments of ADCs using these new platform linkers in cynomolgus monkeys demonstrated showed better tolerability than ADCs using the traditional drug linkers.In summary, our novel ADC platform enables conjugation of hydrophobic payloads at high DARs as high as 8 or 16 with favorable physiochemical properties, results in robust pharmacokinetics, strong potency in vivo, and better tolerability. Therefore the potential for a meaningful therapeutic window may be realized through this novel ADC platform. Citation Format: Haidong Liu, Wenke Qi, Lei Wang, Guobao Wang, Xinyue Chen, Julia Gavrilyuk, Tae Han, Baiteng Zhao, Xiao Shang. Novel ADC platform delivers promising in vivo activity and safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1405.

Abstract LB066: Targeting low density lipoprotein receptors in the pancreatic adenocarcinoma

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor 5-year overall survival rate at all stages of disease (7-10%). The immunohistochemistry of pancreatic cancer tissue has shown a significantly higher level of positive LDLR (low-density lipoprotein receptor) staining in primary tumors compared to the normal adjacent pancreas. LDLR is overexpressed in the epithelial pancreatic adenocarcinoma, irrespectively of tumor size, stage, and aggressiveness. The objective of this study was to determine the LDLR-targeting properties of 68Ga-labeled peptide conjugate, 68Ga-RMX-VH, in pancreatic adenocarcinoma cell lines. Methods: RMX-VH peptide conjugate (25-50μg) was labeled with 68Ga (50-100mCi, ITM Germany) in mild conditions in the presence of scavenger, sodium ascorbate (8mg/ml). The cellular uptake and competition studies of the radiotracer (15μCi/well) were completed in multiple pancreatic adenocarcinoma cell lines and in vivo in PDAC xenografts generated in athymic nude mice. The PET/CT images were acquired using a G4 PET/X-ray camera (Sofie Biosciences; 10min/scan) at 1h, 2h post-injection. This study determined in vivo and in vitro time-dependent accumulation of this agent in LDLR-overexpressing pancreatic adenocarcinoma cells. Results: 68Ga-RMX-VH was synthesized with higher than 95% radiochemical purity. The radiotracer was incubated in pancreatic adenocarcinoma cell lines for 1h and has shown the highest uptake in HPAF-II (6.7%ID/mg) and BxPC-3 (5.3 %ID/mg) and MiaPaCa2 (4.75 %ID/mg), respectively. Western blot showed a variable level of LDLR overexpression in human pancreatic cancer cells. The microPET imaging studies confirmed rapid accumulation and retention of radiotracer in the tumor (1.18 %ID/g) and elimination through kidneys (4.5 %ID/g) and bladder (SUV ratio of tumor to kidneys: 0.21). These results correlate with previously reported retention of the agent in Pk4a pancreatic adenocarcinoma. Conclusions: RMX-VH has the potential to evaluate the role of LDL receptors in pancreatic adenocarcinoma. We have initiated the exploratory clinical study of this agent in LDLR-overexpressing solid tumors, including pancreatic adenocarcinoma. Citation Format: Leo Flores, Xuewei Qu, Cedric Malicet, Pascaline Lecorche, Ebrahim Delpassand, Jamal Temsamani, Izabela Tworowska. Targeting low density lipoprotein receptors in the pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB066.

Optimal Number of Required Points for Evaluation - Interpolation Technique in Complex Basis

According to polynomial evaluation-interpolation technique, first of all, the set of required points, in which interpolation will be executed, must be defined in evaluation part. Taking into account that working in complex domain provides as with the advantage of conjugate properties, the number of evaluations at these points could be reduced. This paper presents the appropriate form of required points, aiming to an optimal reduction of their amount. The appropriate form of points for two variable polynomials depends on the degree of each variable. As a repercussion the number of evaluations could be reduced even up to the half.

Novel Therapeutics Involving Antibiotic Polymer Conjugates for Treating Various Ailments: A Review.

Antibiotic polymer conjugates (APCs) are an essential part of polymer therapeutics. These conjugates have been used as an appealing platform for drug delivery. As a delivery vector, the administration route severely impacts the accessibility of antibiotics to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of conjugates also correlate distinctly with the route of administration. The APCs delivery methods that have been disclosed so far suffer from significant constraints due to poor technology and constrained administration routes (mainly injections). Leading to promising directions, which include the development of specific characteristics for each polymer carrier, application of novel biodegradable polymers, expansion of traditional drug administration routes through the development of emerging routes, and the development of a rational and systematic methodology for designing administration routes are yet to be explored widely. This review focuses primarily on recent improvements in various routes of administration (dental, topical, and ocular) employing APCs. The mechanism of action, as well as other perspectives, have also been discussed. Moreover, this innovative technology provides a fresh perspective on pharmaceutical science research and offers unique and potential pathways for designing desired APCs.

Preparation methods and biocatalytic properties of covalent conjugates of rhodospirillum rubrum l-asparaginase

Preparation methods and biocatalytic properties of covalent conjugates of rhodospirillum rubrum l-asparaginase

Structure and electronic properties of the HA-CUR conjugate: An insight from the DFT perspective

In this article, we are reporting the results of the first detailed Density Functional Theory (DFT) study of the structure of the hyaluronic acid-curcumin (HA-CUR) compound. The molecular orbitals (MOs), frontier molecular orbitals (FMOs, i.e., energies of the FMOs and HOMO/LUMO gaps), and molecular electrostatic potential (MEP) of the compound have been investigated using the Gaussian 09 package using the hybrid functional B3LYP with the split-valence polarized 6-311G(d,p) basis set (B3LYP/6-311G(d,p) approach). In addition, the NBO (Natural Bond Orbital) charge analysis and NBO bonding analysis for the HA-CUR complex have been performed. The structures of the HA and CUR moieties inside the HA-CUR complex are found noticeably different from their free molecules, and the LUMO of the HA-CUR complex is noticeably stabilized compared to the HA LUMO and to the CUR LUMO, which leads to the noticeable closure of the HA-CUR HOMO/LUMO gap compared to the HA gaps and CUR water-computed gap. The detailed studies carried out on the HA-CUR complex in different aspects will definitely be useful for the researchers working in the area of the novel drug design and pharmaceutical chemistry.

Characterization of β-Glucan-Peanut Protein Isolate/Soy Protein Isolate Conjugates and Their Application on Low-Fat Sausage.

Polysaccharide–protein conjugates can improve the functional properties and expand the application field. The emulsifying, thermal properties of WSG-PPI conjugates and WSG-SPI conjugates were improved, compared to WSG, PPI and SPI. The Maillard reaction was confirmed by Fourier transform infrared spectroscopy (FT-IR). Circular dichroism (CD) exhibited that the structure of the conjugates was more expanded. Cryo-SEM and AFM demonstrated that the WSG, WSG-PPI and WSG-SPI conjugates had a morphology of a chain. When the conjugates were added as fat substitutes to low-fat sausage, the cooking yield, hardness and chewiness increased. The objective of this research was to study the emulsifying property, thermal property and structural changes of β-glucan-peanut protein isolate (WSG-PPI) conjugates and β-glucan-soy protein isolate (WSG-SPI) conjugates prepared through wet-heated Maillard reaction, and their effect on the texture of low-fat sausage.

The impact of browning intensity on interfacial properties of gellan gum-soy protein conjugate obtained through the Maillard reaction

The impact of browning intensity on interfacial properties of gellan gum-soy protein conjugate obtained through the Maillard reaction

Comparative experimental and DFT analysis of novel indole tagged [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrid

A novel indole tagged [1,3,4]thiadiazole-pyrimidin-5-one was synthesized using the [4+2] cycloaddition reaction between the 1,3,4-thiadiazole-tethered 1,3-diazabuta-1,3-diene and indole-ketene. The compound was structurally elucidated using different spectroscopic techniques (NMR, IR, and HRMS). The single-crystal X-ray diffraction analysis revealed that the molecule (6) (C19H11BrN4OS) was crystallized in a monoclinic space group with the unit cell factors, a = 14.6166(7) Å, b = 7.1516(4) Å, c = 17.1037(9) Å, α =g = 90°, b = 111.893(2)°, V = 1658.95(15) Å3 and Z = 4. The Hirshfeld analysis further disclosed that the H…H, C…H/H…C, and BR…H/H…BR contacts were the most significant contributors among the interacting atoms in the X-ray structure. Additionally, the geometrical and electronic properties of the molecular conjugate computed at the density functional theory (DFT) level in its ground state displayed a good linear correlation with the single-crystal XRD data. Additionally, the UV absorption band of 6 was observed to be due to the n→π* transition.