Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• Senze Qiao Zhongyu Cheng Fuzhuo Li Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai, 201203, China Key Laboratory of Smart Drug Delivery (Ministry of Education), State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 201203, China 10.3762/bjoc

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• represents prototypes of molecular machines in which guest binding is regulated by stimuli-induced conformational changes between open and closed states (Figure 1). This feature holds significant promise for applications in sensing, drug delivery, or membrane transport within biological systems. Moreover

• and drug delivery systems [12]. pH-Responsive molecular tweezers A particular case of coordination-responsive systems is when a proton is used as a stimulus leading to pH-responsive systems with the protonation/deprotonation of the switchable moiety. The conformational switch in these systems is

• arms, can encapsulate planar aromatic molecules, making this system promising for drug delivery. The advancement of pH-switchable molecular tweezers laid the groundwork for the development of switchable lipids [20]. When such lipids are incorporated in lipid vesicles, they provide means for controlled

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• crystallization of host–guest complexes and their crystallographic analysis. Keywords: anisotropy; 13C NMR; cyclodextrin; host–guest complexes; Introduction Complexation of organic and inorganic compounds with α-, β-, or γ-cyclodextrins and their derivatives [1] is an established tool used in medicine for drug

• delivery [2][3][4], in analytical and preparative chemistry for compound separation [5] and in materials science for small molecule detection [6][7]. Association (binding) constants between the host and guest molecules [8][9][10] are typically measured by 1H NMR titration [11][12] or isothermal titration

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• Yumei Wang Guangzhu Wang Yanping Zhu Kaiwu Dong School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Shandong

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• [12], and drug delivery [13]. In spite of the important advancements in this field, the synthesis and characterization of these fascinating, complex molecules remains an important challenge and often requires intricate synthetic approaches. After the first templated synthesis of a [2]catenane

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• fields, mainly in drug delivery where they are used as pharmaceutical excipients to increase the drug permeability through biological membranes improving drug bioavailability and efficacy [2][4][5]. Furthermore, the CDs peculiarities helped to develop a combined system in which CD–guest complexes are

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• ], amino alcohols [10], and amino acids [11] have been studied due to their potential applications in supramolecular chemistry, drug delivery, and molecular recognition. The complexation of R[4]A with amines is based on the formation of hydrogen bonds between the hydroxy groups of the resorcinol units and

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• form various host–guest inclusion complexes [16][17][18][19][20], which have broad application prospects in supramolecular catalysis [21][22][23], molecular recognition [24][25], and drug delivery [26][27]. In recent years, in the field of supramolecular chemistry, the detection of analytes based on

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• fluorescence emission based on CS-TPE or TBTQ-C6/CS-TPE may find applications in various fields, including the development of visual oral drug delivery systems. Keywords: chitosan; nanoparticle; tetraphenylethylene; tribenzotriquinacene; Introduction Stimuli-responsive assemblies in aqueous media have drawn

• stimuli, pH response is of particular interest in the construction of supramolecular systems for intelligent drug delivery because of the presence of pH gradients in the microenvironment of organs, tissues, and cell organelles [5]. In the past years, pH-responsive and other stimuli-responsive

• stimulus-responsive supramolecular vesicles and molecule-scale drug carriers are considered to have potential for cancer drug delivery. However, such supramolecular systems are not suitable for oral administration, which is a convenient and patient-preferred method of drug delivery, especially for patients

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• )porphyrin 130a,b and 6-deoxy-6-azido-PM-β-CD 124 using copper sulfate and sodium ascorbate in THF/H2O (Scheme 26). Furthermore, the supramolecular nanoarchitectures as potential candidates for controlling drug delivery were prepared by complexing the porphyrins 131a,b with tetrasodium

• -soluble nanowires, nanorods, and nanospheres. In addition, these triazoloporphyrins have a wide range of medical applications, including photoinduced cytotoxicity against cancer cells, drug delivery, as phototherapeutic agents, and PDT applications. I believe this review will be useful and encourage

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• biomedical applications in, e.g., drug delivery systems, tissue engineering and more. Commonly, the synthesis of poly(2-oxazoline)s involves problematic organic solvents that are not ideal from a safety and sustainability point of view. In this study, we investigated the cationic ring-opening polymerization

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• in cancer-related deaths. With the current treatment possibilities, a definitive, safe, and effective treatment approach for CRC has not been presented yet. However, new drug delivery systems show promise in this field. Amphiphilic cyclodextrin-based nanocarriers are innovative and interesting

• -loaded polycationic-β-cyclodextrin nanoparticles caused reduced cell viability in CT26 and HT29 colon carcinoma spheroid tumors of mice and human origin, respectively. In addition, the release profile, which is one of the critical quality parameters in new drug delivery systems, was investigated

• , there is an intense focus on oral drug delivery, especially in the treatment of chronic diseases such as cancers. Even though there have been many developments in the field of chemotherapy in recent years, both in terms of diagnosis and treatment, oral chemotherapy has not yet been fully achieved due to

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• : cyclodextrin; complexation; 17β-estradiol; progesterone; solubility; X-ray diffraction; Introduction The insolubility of active pharmaceutical ingredients (APIs) and other bioactive compounds in aqueous media and the associated challenges for effective drug delivery are well known to have beleaguered the

• derivatised CDs containing BES and PRO, thus confirming the sustained interest in this approach and its significance in drug delivery. Previous studies of the complexation of BES, PRO and related compounds by CDs in the solution phase have typically reported the use of NMR spectroscopy to investigate complex

• relatively low cost of these CDs and in particular the low toxicity of γ-CD are advantageous for potential drug delivery. Furthermore, the amorphous nature of highly water-soluble CD derivatives (e.g., hydroxypropyl-CD and sulfobutyl ether CD) precludes their formation of crystalline inclusion complexes

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• , they are less common due to their inherent toxicity and ease of oxidation. Another branch of research involving SPIONs focuses on developments in nanoscience, nanomedicine, and nanoparticle-assisted imaging, diagnosis, and drug delivery [4][5][6][7], an area that is not covered in this report. Review 1

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• novel TBTQ-based host–guest drug delivery system may have potential use in supramolecular chemotherapy. Keywords: competitive substitution; drug delivery; host–guest chemistry; tribenzotriquinacene; water soluble; Introduction Chemotherapy is considered to be one of the most effective strategies in

• spectroscopy. The competitive binding of TBTQ-CB6 to SM was revealed by NMR titration. In essence, this represents the first application of the convex-concave TBTQ motif for potential use in drug delivery systems. Results and Discussion Synthesis and characterization of host TBTQ-CB6. The host TBTQ-CB6 was

• of SM, as confirmed by 1H NMR titration experiments. This host–guest competitive substitution system may have potential applications in controlled drug delivery. Experimental General information. All commercially available reagents were used as received unless otherwise specified. Anhydrous solvents

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• merits, such as ease of design and tailoring (based on the known structures from proteins), good biocompatibility and degradability, and low immunogenicity. For example, recent works have demonstrated the potential of peptide assemblies for a wide range of applications, including drug delivery [8][9][10

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• . Chitosan is one of the most abundant bio-based polymers in nature [9]. It is the N-deacetylated form of chitin found in industrial waste [10]. Chitosan is a broadly used natural polymer because of properties such as biocompatibility, low cost, and nontoxicity. It has diverse applications, such as drug

• delivery [11], biomedical uses [12], removal of toxic metals from wastewater [13], in manufacturing processes [14], in the food industry [15], in agriculture [16], and as catalyst in transesterification reactions [17]. Chitosan is regarded as one of the most effective bio-based polymers to chelate

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• domains, such as chemosensors [21], drug delivery [22], and nano materials preparation [23]. Although cucurbiturils with their rigid hydrophobic cavities have found broad application in host–guest chemistry, they suffer from insolubility, difficulty in derivatization, and lack of chromophores

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• structure stacking diagram of the CPE@Q[8] host–guest complex along the c-axis. It can be clearly seen that small hexagonal holes are formed between the complexes, which are expected to have potential applications in molecular adsorption and drug delivery. UV–visible spectroscopy The interaction between Q[8

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• nanostructures in solution have received increasing attention during the last two decades, related to the high surface-to-volume ratio, which is particularly attractive for targeted carrier materials in biomedical applications. In addition, cylindrical drug delivery vehicles appear to be advantageous compared to

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• solvent below freezing temperature. Due to their inherent interconnected macroporosity, ease of preparation, and biocompatibility, they are increasingly being investigated for use in biomedical applications such as 3D-bioprinting, drug delivery, wound healing, and as injectable therapeutics. This review

• implantation without surgical incision, and use as highly effective wound dressings. Furthermore, conclusions and outlooks are discussed for the use of these promising and durable macroporous cryogels. Keywords: 3D-bioprinting; cryogels; drug delivery; injectable cryogel; macroporous hydrogel; wound healing

• cell proliferation and waste exchange, e.g., in a scaffold for tissue engineering applications [3]. Novel biomedical and biotechnical applications of cryogels can also be found in controlled drug delivery, carriers for cell immobilization, sensors, bioseparation, purification, and wound dressing [4][5

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• outcomes, illustrating the complexity in understanding and designing efficient drug-delivery systems in biological environments. It needs to be considered that TPP, despite its positive charge, still carries large phenyl groups that render the surface hydrophobic. While this can affect protein adsorption

• , it is more important to understand how TPP is presented on the surface of these PISA particles. In order for TPP to fulfil its function, the surrounding of the ligand needs to be considered. Cartoons are widely used in the drug delivery literature, often showing the targeting ligand readily available

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• , have been intensively studied in solution. For the application of such polymers in novel sensors, drug delivery systems or as multifunctional coatings, they typically have to be transferred into specific arrangements, such as micelles, polymer films or grafted nanoparticles. However, it turns out that

• including biomedicine [29][30], drug delivery [12][31], tissue engineering [32][33], analytic application [18], environmental applications [34][35], sensors [36][37][38], actuators [37][38][39] and other applications [5]. For many of these purposes, it is essential to tether such polymers to interfaces or

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• comparative sample was prepared by the same procedure in the absence of g-CN. Hydrophobic hydrogels Recently, utilization of hydrogels in nutrient delivery in agricultural science and long-term drug delivery exhibits a significant interest [43]. Most of these methods require aqueous formulations to be

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• acids (H-HAIYPRH-NH2) was identified via phage display [24] and has a high affinity (≈10 nM) for the transferrin receptor [24][25]. This peptide does not compete with endogenous transferrin binding and has been used to successfully enhance drug delivery to brain tissue [15][22][24][25][26]. Both

• specificity are needed to expand the use of LNPs for gene and drug delivery. LNPs and aptamers have previously been used with great success to increase cell specificity. In 2015, Liang et al. reported on a novel aptamer–LNP targeting osteoblasts. The authors conjugated aptamers to a 1,2-distearoyl-sn-glycero

• , effective transport systems for brain drug delivery are highly warranted. Herein, we find that the LNP platform can be applied as a vehicle to circumvent the BBB and effectively deliver oligonucleotide probes to antigen-expressing cell lines. For HIV-1 there is currently a need for more effective delivery