Biomedical Chemistry Research Articles

Green Synthesis and Applications of Nanoparticles in Biomedical Chemistry

AbstractNumerous case studies have shown that nanoparticles (NPs) can help address raw material challenges in biomedical as well as healthcare‐related fields. The NPs derived from metal as well as metal oxide have exhibited remarkable therapeutic potential in clinical research. The strategies for nanomaterials interaction with cells can be employed to demonstrate their significance as well as enhance their optimistic potential in the health as well as medical domain. There have been numerous scientific initiatives to discuss antibiotic resistance as well as the antibacterial properties of metal‐based NPs. Regardless of such advancements; there is still a need to investigate their achievement to address current challenges in this field. Thus, this review looks into the contributions of various types of nanoparticles, as well as potential biological and biomedical applications. According to recent advancements as well as applications, metal oxide, and metal‐based NPs are predicted to play a significant part in the healthcare system. The opportunities, as well as challenges for NP commercial advancement, are linked to improving production with optimized scenarios.

Clinical metabolomics: current state and prospects in Russia.

Using analytical technologies it is possible now to measure the entire diversity of molecules even in a small amount of biological samples. Metabolomic technologies simultaneously analyze thousands of low-molecular substances in a single drop of blood. Such analytical performance opens new possibilities for clinical laboratory diagnostics, still relying on the measurement of only a limited number of clinically significant substances. However, there are objective difficulties hampering introduction of metabolomics into clinical practice. The Institute of Biomedical Chemistry (IBMC), consolidating the efforts of leading scientific and medical organizations, has achieved success in this area by developing a clinical blood metabogram (CBM). CBM opens opportunities to obtain overview on the state of the body with the detailed individual metabolic characteristics of the patient. A number of scientific studies have shown that the CBM is an effective tool for monitoring the state of the body, and based on the CBM patterns (signatures), it is possible to diagnose and monitor the treatment of many diseases. Today, the CBM creation determines the current state and prospects of clinical metabolomics in Russia. This article, dedicated to the 80th anniversary of IBMC, is a review of these achievements focused on a discussion of their implementation in clinical practice.

Co-trimerization of benzonitriles with guanidine hydrochloride: synthesis of 2-bromo-4,6-diaryl-1,3,5-triazine derivatives bearing electron-withdrawing groups

Abstract In recent decades, various types of aryl-substituted 1,3,5-triazine derivatives have been applied in many research fields, including biomedical chemistry, non-linear optics, and organic electronics. However, the substituent scope for 4,6-diaryl-1,3,5-triazines (DAr-TRZs) remains limited. Here, we present our work on the synthesis of 2-amino- and 2-bromo-DAr-TRZ derivatives bearing electron-withdrawing groups on the aryl rings. Our synthetic methods successfully provided trifluoromethyl-, nitrile-, and nitro-substituted DAr-TRZs. These will expand the structural diversity of conventional triazine-based functional materials.

Palladium Catalyzed Carbonyl Amination of Fluorinated Olefins for Synthesis of α‐CF3‐Acrylamides

AbstractAcrylamides are a class of important organic compounds that play key roles in biomedical chemistry, materials science, life science, and other fields. Due to the strong electron‐withdrawing effect of trifluoromethyl, the synthesis of trifluoromethylated acrylamides, especially those containing double bonds, has long been a challenge. Here, we report an example of the formation of trifluoromethyl acrylamides through palladium catalyzedcarbonylation of fluorinated olefins. By optimizing the reaction conditions, we can obtain different amide compounds, including alkyl acrylamides. aromatic acrylamides and heterocyclic acrylamides. This method has good substrate adaptability and functional group tolerance,so it is expected to be used in the synthesis of key amides in the fields of medicine and other fields.

Reductive Functionalization of Pyridine-Fused N-Heteroarenes.

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair-induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C-H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H2 gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, β, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

The Process of AI-Aided Drug Design

Artificial Intelligence (AI) is a growing field in today’s world and plays a part in many industries today. Its role in drug design and the biological sciences has begun to expand in recent years. DeepChem is an open source tool that explores and employs the methods behind drug design. The tool’s process and end result will be indicative of how well AI can perform the job of drug discovery and how much it can expedite the process, as well as reveal the future of tools like DeepChem. DeepChem handles everything from data processing to fitting AI models to performing predictions on proposed molecules. By applying DeepChem and reviewing it, we will be revealing AI’s power and limitations in biomedical chemistry and technology. In addition, other AI tools, such as Chemistry 42 and inClinico by Insilico that achieve other parts of the drug design process. Completing a comprehensive review of these methods will provide an overview of what can be improved and the scope of AI as a big money-maker and solution in the biomedical field. The synthesis of drugs is a complicated process that can be simplified by AI tools. This paper explores how AI tools operate and their limitations in the medicinal world.

Comparative Study of the Antibacterial and Cytotoxic Activity of Leaves, Trunk and Roots of Schumanniophyton Magnificum

Aims: Schumanniophyton magnificum is a plant reputed traditionally to treat numerous urogenital infections linked to several germs, notably: Escherichia coli, Staphylococcus aureus, Neisseria gonhorhea, Treponema palidum, Candida albican. This study aims to evaluate and compare the in vitro antibacterial and cytotoxic activities of the leaves, trunk and roots of S. magnificum in order to determine the parts displaying the best activity.
 Study Design: This is an experimental study.
 Location and Duration of the Study: The work was conducted at the Pharmacochemistry and Natural Substances Laboratories of the Faculty of Medicine and Pharmaceutical Sciences, University of Douala for the extraction and at the Medical Analysis Laboratory of the Douala General Hospital for antibacterial test as well as Biomedical Chemistry Research Center of Rhodes University in South Africa for cytotoxic essay. All the experiments were carried out from the 15th November 2020 to the 31th May 2021.
 Methodology: The in vitro Antibacterial activity essay was conducted on two strains, one Gram+ bacteria: Staphylococcus aureus and one Gram- bacteria: Escherichia coli, while cytotoxicity was evaluated on HeLa cell line.
 Results: The root wood extract and the root bark extract presented a good antibacterial activity (MIC = 195.31 µg/mL) and average activity (MIC = 390.63 µg/mL) respectively with E. coli. The different extracts were found to be bactericidal against the tested micro-organisms. At the concentration of 20 µg/mL, all extracts tested did not significantly reduce HeLa cells, with an inhibition rate ranging from 13.5 to 37.6%, suggesting a low cytotoxicity of S. magnificum extracts towards these human cells line.
 Conclusion: This is the first comparative report on the antibacterial and cytotoxic study conducted on the different parts of S. magnificum. It appears from this study that these results could justify the use of the stem bark of S. magnificum in the traditional pharmacopeia for the treatment of urogenital infections. However, the roots wood having presented the best antibacterial activity (MIC = 195.31 µg/mL), it would be beneficial to suggest this plant part to the local populations for the treatment of bacterial diseases specific to E. coli and S. aureus, after the preclinical and clinical tests are carried out.

Synthesis of α-CF3 Amides via Palladium-Catalyzed Carbonylation of 2-Bromo-3,3,3-trifluoropropene.

Amide compounds are important organic compounds, which play an important role in biomedical chemistry, materials science, life science, and other fields. The synthesis of α-CF3 amides, especially compounds containing 3-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepine-2-one, has long been a challenge due to the tensile properties and instability of the rings. Here, we report an example of palladium-catalyzed carbonylation of CF3-containing olefin to form α-CF3 acrylamide. By controlling the ligands, we can get different amide compounds as products. This method has good substrate adaptability and functional group tolerance.

Comparative Anti-plasmodial and Cytotoxic Effect of the Methanolic Extracts of Leaves, Stem Bark and Roots of Annickia affinis

Aims: This study aimed to evaluate and compare the in vitro anti-plasmodial and cytotoxic effect of the methanolic extracts from leaves, stem bark and roots of Annickia affinis.
 Study Design: This is an experimental study.
 Place and Duration of Study: The work was conducted at the Pharmacochemistry and Natural Substances Laboratories of the Faculty of Medicine and Pharmaceutical Sciences, University of Douala for the extraction and at the Biomedical Chemistry Research Center of Rhodes University in South Africa for the antimalarial and cytotoxic essay. All the experiments were carried out from the 15th October 2019 to the 31th July 2020.
 Methodology: The anti-plasmodial test was performed on Plasmodium falciparum sensitive strains 3D7 while cytotoxicity was evaluated on the HeLa cell line.
 Results: The anti-plasmodial tests revealed that the roots and the stem bark exhibited a moderate anti-plasmodial effect with IC50 of 19.7 ± 0.8 and 12.1 ± 0.8 µg/ml respectively. The anti-plasmodial effects of the leaves were classified as low (33.7 ± 1.9 µg/ml). At up to 50 µg/ml, all the extracts showed a high rate of survival among the HeLa cells. No effect was observed with the leaf extracts (100% of survival).
 Conclusion: This is the first report on the cytotoxic study and comparative anti-plasmodial effect of Annikia affinis. It highlights the potential of Annickia affinis as an important source of anti-plasmodial drugs with less cytotoxic in vitro. In agreement with the use in traditional medicine, the stem bark was more active than wood, while leaves showed low activity.

The potential protein marker of bipolar disorder

IntroductionDifficulties in the diagnosis of bipolar disorder (BD) are associated with a lack of understanding of the mechanisms of its pathogenesis. Identification of proteins involved in the pathogenesis of BD will bring us closer to an understanding of its mechanisms and can help in diagnosis.ObjectivesThe search of proteomic biomarkers of bipolar disorder.MethodsWe performed a proteomic analysis of the serum of 16 healthy people and 33 patients with BD. Patients were hospitalized in an acute state of the depressive phase, and they did not receive therapy for more than 6 months. Blood was collected before the start of therapy. Serum was purified from major proteins by affinity chromatographyandseparatedby1D-electrophoresis. After trypsinolysis, the proteins were identified by HPLC/mass spectrometry. The ELISA kit was used to determine the amount of zNMDAR1.ResultsWe identified a protein that does not occur in healthy people: a subunit of the glutamate NMDA receptor zeta-1 (zNMDAR1). As a result, we found a statistically significant (p = 0.037) almost fivefold increase in the concentration of this protein in the serum of patients with bipolar disorder (0.64 [0.18; 0.78] ng/ml) compared with healthy individuals.ConclusionsThus, in bipolar disorder NMDAR is damaged, which can lead appearance of their subunits in the serum, and which indicated a violation of glutamatergic neurotransmission. Then this protein claims the role of markers of bipolar disorder. Mass spectrometric analysis was carried out of the “Human Proteome” Core Facility of the Institute of Biomedical Chemistry Moscow. RSW project, state registration number AAAA-A19-119020690013-2.DisclosureNo significant relationships.

Marker of schizophrenia with enduring negative symptoms

IntroductionThe relevance of this study is determined by the need to search for biological markers of schizophrenia. The detection and validation of such molecules can become the basis for the creation of additional paraclinical diagnostic methods or contribute to the creation of targets for individual pharmacotherapy, which is an important task of modern fundamental medicine.ObjectivesComparative proteomic analysis of serum in schizophrenic patients with positive and negative symptoms.MethodsThe study includes 10 healthy donors and 27 patients with schizophrenia. Samples preparation included: serum purification from major proteins via affinity chromatography, 1D-PAGE proteins separation, in-gel tryptic hydrolysis, LC-MS/MS mass-spectrometry (Orbitrap Q-exactive HF mass spectrometer, Agilent Technologies). Identification of proteins was carried out using Mascot software Ver. 2.1 («Matrix Science», USA). Proteins for quantitative analysis were selected in view of the DISGENET database. Quantitative LC-MS-SRM analysis of selected protein was performed on QQQ TSQ Vantage (Thermo Scientific) with labeled peptide standards.ResultsReceptor-interacting serine/threonine-protein kinase 1 was selected for quantitative assessment. Significant differences were revealed in the RIPK1 concentrations in the serum of schizophrenic patients with negative and positive symptoms (p=0.02). The serum concentration of RIPK1 in patients with negative symptoms is tenfold in patients with positive symptoms.ConclusionsReceptor-interacting serine/threonine-protein kinase 1 can be considered a biomarker of negative symptoms of schizophrenia based on a significant increase in serum concentration. Mass spectrometric analysis was carried out of the “Human Proteome” Core Facility of the Institute of Biomedical Chemistry Moscow. Support by Grant of RSF № 18-15-00053P.DisclosureNo significant relationships.

Microstructure of spherical granules based on hydroxyapatite and wollastonite

Spherical granules are one of the preferred forms of biomaterials for bone defects healing. Chemical composition and microstructure of these materials are largely determines their behavior in vivo. Synthesis and properties investigation of polydispersed porous composite granular materials containing several bioactive components are the important task of modern biomedical chemistry. In this work, the microstructure of organomineral granules based on hydroxyapatite, wollastonite, and gelatine, and the products of their calcination were studied. It was found that as a result of removal of the polymer binder from the ceramic particles surface, nanopores were disclosed, and the subsequent crystallites sintering provide the granules shape stability.

Biogenic Synthesis of Silver Nanoparticles using Azadirachta indica (Neem) Leaf Extract To Achieve Inhibitory Action Against Antibiotic-Resistant Bacteria

Background: Nanotechnology is an emerging research field on nanoparticles. Nanoparticles are 1-100 nm in one dimension and are important in biomedical science, medical chemistry, atomic physics, and most other known fields. They are used because of their small size, orientation, and physical properties. Objectives: This study was designed to synthesize silver nanoparticles (AgNPs) using Azadirachta indica (Neem) leaf extract and evaluate their biomedical application. Methods: An aqueous extract of Azadirachta indica was used to synthesize AgNPs. 1 ml of the extract was added drop by drop to 30-60 ml of a 1mM solution of silver nitrate. The AgNPs were characterized by UV-Visible Spectroscopy, Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering Spectroscopy, X-ray Diffraction, Transmission Electron Microscopy, and antibacterial activity studies. The biological synthesis of AgNPs was performed using the aqueous solution of Azadirachta indica leaf extract and AgNO3. A fixed ratio of plant extract to metal ion was used to prepare AgNPs and the formation of the nanoparticles was confirmed through the color change. The nanoparticles were characterized by UV-vis spectrophotometer, FTIR, DLS, XRD and TEM, and were found to range in size from 30-60 nm. Results: The biosynthesized AgNPs had a bactericidal effect against the antibiotic resistant pathogenic microorganisms Bacillus subtilis, Pseudomonas aeruginosa, and Bacillus cereus. Conclusion: Silver nanoparticles were synthesized from Azadirachta indica leaf extract and can be used as a therapeutic candidate for biomedical applications.

Electrochemistry of Quinones with Respect to their Role in Biomedical Chemistry.

Quinones are ubiquitous in nature and form one of the largest class of antitumor agents approved for clinical use. They are known to be efficient in inhibiting cancer cells growth. Under physiological conditions they can undergo non-enzymatic one-electron reduction to give the moderately toxic species of semiquinone radical-anion. Thus, electrochemical study of quinones might provide a basic knowledge on semi-quinone radicals formation in both in vivo and in vitro under different media. Several processes are outlined briefly and discussed in the present article. Previously we investigated the electrochemical and spectral properties of ω-N-quinonyl amino acids. Such quinone-bearing peptides are known to be cytotoxic and of potential clinical significance. We were able to prove that the ω-amino quinonyl compounds are very effective in producing stable semiquinone radicals. Moreover, a direct relation was found between the first reduction potentials of the quinonyl moiety and their reactivity towards the ω-amino acids. In order to increase our knowledge of such amino quinonyl compounds and enlarge the arsenal of such cytotoxic compounds, a series of N,N-diquinonyl amines (1-6) bearing an internal proton (stems from the NH moiety) were synthesized. Their electron-transfer capabilities were probed by cyclic voltammetry measurements, in dichloromethane. It was found that the acidic NH group linking the two quinonyl moieties undergoes an initial electrochemical reduction step and generates a nitride anion. This step is followed by further reductions to yield quasi-stable semiquinone radicals and polyanions, Since these acidic diquinones (1-6) serve also as a source of internal proton donors even in non-polar medium, they might cause protonation of basic radical-anions and polyanion intermediates during the various electrochemical stages. The processes are demonstrated and discussed by analyzing different mechanistic schemes. The successful generation of relatively stable semiquinone radicals is a prerequisite for the manifestation of site directed antitumor activity by these bis-quinonyl amino derivatives. Based on the values of their redox potentials some of them could be promising candidates for clinical development.

Changes in the mitochondrial subproteome of mouse brain Rpn13-binding proteins induced by the neurotoxin MPTP and the neuroprotector isatin

Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson's disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle play an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al. (2020) Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 14, 297-305). In this study we have investigated the effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the neuroprotector isatin on the mitochondrial subproteome of Rpn13-binding proteins of the mouse brain. Administration of MPTP (30 mg/kg) to animals caused movement disorders typical of PD, while pretreatment with isatin (100 mg/kg, 30 min before MPTP) reduced their severity. At the same time, the injection of MPTP, isatin, or their combination (isatin + MPTP) had a significant impact on the total number and the composition of Rpn13-binding proteins. The injection of MPTP decreased the total number of Rpn13-binding proteins in comparison with control, and the injection of isatin prior to MPTP or without MPTP caused an essential increase in the number of Rpn13-binding proteins, mainly of the functional group of proteins participating in the protein metabolism regulation, gene expression, and differentiation. Selected biosensor validation confirmed the interaction of Rpn13 subunit of proteasome with some proteins (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, histones H2A and H2B) revealed while proteomic profiling. The results obtained testify that under the conditions of experimental MPTP-induced parkinsonism the neuroprotective effect of isatin may be aimed at the interaction of mitochondria with the components of UPS.

Chemical Strategies to Enhance the Therapeutic Efficacy of Toll-like Receptor Agonist Based Cancer Immunotherapy.

Recent developments in the fields of biomedical chemistry and immune bioengineering have enabled innovative therapeutic approaches that can enhance the efficacy, accuracy, and safety of cancer immunotherapy. Among the numerous strategies utilized in cancer immunotherapy, Toll-like receptor (TLR) agonist-based approaches have been studied for a long time since they trigger the innate immune system and generate antigen-specific T cell responses to fight against tumors. In addition to these immunostimulatory functions, TLR agonists also contribute to the reprogramming of immune suppressive tumor microenvironments. Although TLR agonists are now being intensively studied in clinical trials due to their substantial immunomodulatory properties, they still show a low therapeutic index. Nonspecific and random stimulation of various immune cells produces excess levels of proinflammatory cytokines, resulting in cytokine storms and chronic diseases. Therefore, the development of chemical strategies to enhance the therapeutic efficacy as well as the safety of TLR agonist-based immunotherapy is essential and in high demand.In this Account, we summarize and discuss recent developments in biomedical chemistry and bioengineering techniques for the immunomodulation of TLR agonists that have addressed the limitations in current cancer immunotherapy. Immunomodulation of TLR agonists can be classified into two different approaches: (1) molecular modulation via chemical structure modification and (2) macroscopic modulation via an engineered drug delivery system. In molecular modulation, based on prodrug and antedrug principles, activity is modulated (active or inactive) through immolative chemical linkers that can respond to extrinsic or intrinsic biological stimulation and the plasmatic environment, respectively. To increase the effectiveness of TLR agonists as immunostimulatory agents, researchers have conjugated TLR agonists with other immunotherapeutic moieties (antigen, antibody, other TLR agonist, etc.). For macroscopic modulation, bioengineering of delivery carriers differing in size or with albumin hitchhiking moieties has been utilized to increase the efficiency of the targeting of these carriers to secondary lymphoid organs (lymph nodes (LNs) and spleen). The conjugation of specific targeting ligands and incorporation of stimulus-triggering moieties can promote the delivery of TLR agonists into specific cells or intracellular compartments. Implantable porous scaffolds for specific immune cell recruitment and in situ depot-forming gel systems for controlled release of immunomodulatory drugs can increase the therapeutic efficacy of TLR agonists while reducing systemic toxicity. Taken together, these findings show that well-designed and precisely controlled chemical strategies for the immunomodulation of TLR agonists at both the molecular and macroscopic levels are expected to play key roles in improving the therapeutic efficacy of cancer immunotherapy while minimizing immune-related toxicity.

Poly (alanine)/NaOH/ MoS2/MWCNTs modified carbon paste electrode for simultaneous detection of dopamine, ascorbic acid, serotonin and guanine

The detection of biomolecules such as dopamine (DA), ascorbic acid (AA), serotonin (5-HT), and guanine (GU) is essential for biomedical chemistry and disease diagnosis. In this work, MoS2/acid-treated MWCNTs composite (Ms-atCNTs) was first prepared and then used to modify carbon paste electrode (CPE), followed by electropolymerization of alanine in the presence of NaOH. The resulting modified electrode (p-Aln/Ms-atCNTCPE) was tested for the simultaneous detection of DA, AA, 5-HT, and GU using cyclic voltammetry and differential pulse voltammetry in phosphate buffer solution (PBS). The p-Aln/Ms-atCNTCPE showed excellent electrochemical response towards the detection of DA, AA, 5-HT, and GU. The electrode was also effectively utilized for concentration variation studies of a mixture containing these biomolecules. The detection limits were found to be 0.08 μM, 3.9 μM, 0.1 μM, and 0.1 μM for DA, AA, 5-HT, and GU, respectively. Furthermore, the proposed sensor displayed favorable repeatability, stability, and selectivity, as well as the usefulness for the detection of target molecules in real samples, such as DA injections, vitamin C tablets, herring sperm DNA, and human blood serum.

First person – Maiko Yamamoto

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Maiko Yamamoto is first author on ‘The PRDM14–CtBP1/2–PRC2 complex regulates transcriptional repression during the transition from primed to naïve pluripotency’, published in JCS. Maiko conducted the research described in this article while a Master course student in Yoshiyuki Seki's lab at Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, investigating epigenetic regulation of ESC pluripotency.

Unique Self-Assembly of Sequence-Controlled Amino Acid Derived Vinyl Polymer with Gradient Thermoresponsiveness along a Chain.

A novel water-soluble amino acid derived vinyl polymer whose block sequence was designed to achieve a gradient thermoresponsiveness along a chain was accurately prepared through an ultrarapid reversible addition-fragmentation chain-transfer polymerization. The polymer exhibited unique temperature-regulated self-assembly in water, leading to multiple nanostructural transformations including disassembly-to-ordered and ordered-to-ordered transitions. The morphologies were drastically changed by heating the solution from 4 °C (soluble form) to 20 °C (spherical micelle) to 70 °C (vesicle). Moreover, such transitions exhibited hysteresis upon cooling, namely, from 70 °C (vesicle) to 20 °C (wormlike micelle) to 4 °C (soluble form). In this polymer system, the specific monomer sequence contributed to the self-assembly behavior. These findings provide significant insight into the design of new thermoresponsive nanomaterials with potential applications in biomedical chemistry.

Tunable UCST thermoresponsive copolymers based on natural glycyrrhetinic acid

Water-soluble thermoresponsive polymers present either upper critical solution temperature (UCST) or lower critical solution temperature (LCST) depending on the location of their miscibility range with water at high temperatures or at low temperatures. Compared with LCST polymers, the water-soluble UCST polymers are still less explored until now. In this work three copolymers of P(AAm-co-GAA) were synthesized by copolymerizing two acrylamide monomers, acrylamide (AAm) and acrylamide functionalized with natural glycyrrhetinic acid (GAA), using reversible addition-fragmentation chain transfer (RAFT) polymerization. These copolymers exhibited the typical UCST thermoresponsive behavior, and their phase transition temperatures could be easily tuned to around 37 °C for potential biological applications. Moreover, the UCST of P(AAm-co-GAA) can be adjusted not only by the content of glycyrrhetinic acid (GA) and polymer concentrations, but also by the host-guest interactions between GA and cyclodextrins (β- and γ-CD). The suitable value of UCST and the biocompatible nature of GA and CDs may endow these copolymers with practical applications in biomedical chemistry