Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• for nucleotides sensing through a dye replacement procedure. It is unusual that disubstituted macrocycles 10a,b bind more effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'-triphosphate (ATP). A simple colorimetric method based on polydiacetylene vesicles decorated with 10b

• vesicles [41]. The inflection point in the plot of EY λmax vs surfactant concentration should be treated as the CAC of the amphiphile [42]. As can be seen from Table 1 the CAC values determined by the two methods are significantly different, especially in the case of macrocycles 10a,b. These differences

• the aggregate. Therefore, a different packing of aggregates is the main reason for the observed ADP/ATP selectivity of calixarene 10b. Polydiacetylene–10b vesicles for ADP/ATP sensing Polydiacetylenes (PDAs), alternating ene-yne conjugated molecules, induce a blue-to-red color transition by the

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• of this class, bafilomycin A1 (Figure 3) is a useful biochemical tool as it prevents the re-acidification of synaptic vesicles once they have undergone exocytosis [14]. Bafilomycins are also known to be cytotoxic, inhibitors of autophagy, active against Gram-positive bacteria, yeast and fungi

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• , which were probably representing vesicles, since an endocytotic uptake pathway for this CPP and its longer version sC18 was already demonstrated [13][18][19]. In addition, the nuclear localization sequence N50 alone was not noticeable present within both cell lines at the tested concentration (Figure S6

• high enough to escape from the vesicles and to reach the nuclei. This might indicate that a certain concentration threshold is indispensable for efficient internalization, a phenomenon that was already discussed for other CPPs [29][35]. Considering all these observations, it was presumed that the

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• . Fluorescence microscopy revealed a cytoplasmic localization of the oligonucleotide without accumulation in the nuclei. This indicated an endocytotic uptake mechanism with (at least partial) retention of the material in the endocytotic vesicles. No unspecific cytotoxic effect of the guanidinylated

• nuclei, thus pointing to endocytotic uptake with retention of the compound in endocytotic vesicles (vide supra). Cationically functionalized phosphorothioates of type 20 were also prepared as diastereomerically pure compounds with defined configuration at the stereogenic phosphorothioate unit [48]. A

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• investigations. The results indicate that Dau-containing metabolites can be found in high amount in the nuclei after already 10 to 30 minutes, whereas the CLSM images after 1 and 5 minutes display the Dau signal predominantly in small cytosolic vesicles. We supposed that the smaller cytosolic compartments seen

• ). The remaining vesicles which display only the Dau signal are assumed to be endosomes. Based on these findings it can be concluded that our lead compound K2 is uptaken through an endocytic pathway. Receptor blockage by triptorelin In order to investigate if the bioconjugate K2 is uptaken in a receptor

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• , namely: (polymer) vesicles, micelles, dendrimers and nanogels. The ability and efficiency of catalytic nanoreactors to carry out organic reactions in water, to perform cascade reaction and their ability to be recycled will be discussed. Keywords: catalysis; dendrimers; green chemistry; nanogels

• membrane. Furthermore, the nanosystem also facilitated catalyst recycling by normal extraction. 2.2. Polymeric vesicles Polymeric vesicles or polymersomes are synthetic bilayered hollow architectures that are self-assembled from amphiphilic block copolymers [73]. The synthetic nature of polymersomes allows

• -isopropylacrylamide)-b-poly(ethylene oxide) (PNIPAM-b-PEO) [78]. The term “polymersomes” is derived from liposomes because of the structural resemblance. Compared to liposomes, polymersomes are mechanically robust vesicles and therefore considered to be highly attractive for nanoreactor applications [24][40

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• . Moreover, confocal microscopy studies showed that the positively charged oligoT escaped endosomal vesicles and migrated to the nucleus of Vero or GC-2 cells. This observation may support the correlation between cellular uptake and the activity of thermosensitive DNA prodrugs. Supplementary experiments with

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• then yielded the DBCO-AuNPs. When these DBCO-AuNPs were treated with azide-decorated polymersomes (a class of artificial vesicles) [58], the AuNPs were successfully attached to the surface of the polymersomes (Scheme 6). Workentin and co-workers have also reported the successful use of SPAAC to

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• ]. The group of Ravoo also conjugated arylazopyrazoles to amphiphilic cyclodextrin derivatives that form vesicles triggered by light [17]. A star-shaped polycationic CD derivative with many breakable, intrinsic, disulfide linkages forms nanoparticles with messenger RNA and drugs and is particularly

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• properties, as glycerophospholipids comprise elements of fluid membrane [5] and nanoscale vesicles called liposomes [6]. In addition, the chiral sn-glycerol backbone is composed of acyclic polyols that produce several conformers through the free rotation about each of the C–C single bonds. For example, the

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• acids and permit their oligomerization, as well as to synthesize other compounds essential to life, such as amphiphiles, the proposed building blocks of prebiotic compartments, which can then self-assemble into vesicles under the same experimental conditions [48]. Pyrophosphites could thus be considered

• acid monomers has been achieved in this manner: When amphiphile vesicles or liposomes are dried in the presence of solutes on a silicate support, a system of stacked lipid bilayers with intercalated solutes is formed [52]. In this arrangement, the nucleotides are optimally spaced to react and form

• nucleic acid oligomers [53][54][55]. The presence of the mineral support is crucial here as it permits the preservation of the amphiphile bilayer structure during drying, thereby promoting the conversion of an “unreactive” organization (free floating vesicles and free monomers) into reactive chemical

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• functional capacities (see [15] for a review). In particular, fatty acid vesicles have become the standard protocell model, not just because of their prebiotic plausibility [27][28], but also because of their remarkable stability as compartments [29][30]; their rapid self-assembly kinetics and amenability to

• -assembling vesicles of different composition [37][38][39] constitutes an important proof of principle that biochemistry can be carried out within strongly simplified compartments, these experiments tell us very little about the actual process of origins. A major challenge that must be tackled in order to

• move the field of origins of life forward would be to couple simple chemistry to prebiotic vesicle dynamics: chemical reactions provide the power for endogenous synthesis and vesicles the adequate scaffolding for the functional integration of what is synthesized. We will proceed briefly with the issue

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• formulation (ratio 4:4:1:1, respectively). A hydrophobic film prepared by evaporation of a lipid–chloroform solution was hydrated with physiological solution. The desired unilamellar vesicles were obtained by homogenization of the dispersion through a 100 nm pore size polycarbonate filter. Characterization of

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• membrane differs during states of growth and non-growth. The former implies a constructive function of the membrane. Proteins are the effectors of this function with the key operation of allowing protein insertion within the membrane. Studies investigating spontaneous evolution of lipid vesicles showed

• autocatalytic cycles producing and retaining a limited dictionary of building blocks enclosed in lipid vesicles made semi-permeable by peptides. These chemical reactions required functional catalytic power to handle substrates and reject products for further manipulation. The swinging-arm conjecture is a

• building up RNA [67]. The first cells and their descent In the same way as coacervates can multiply compartments within a single entity [16], phospholipid vesicles form a variety of cell structures, involving vesicle

Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• different lipid environments: the mechanosensitive probes (1.3 mol %) were added to large unilamellar vesicles (LUV) of either DPPC (dipalmitoyl-sn-glycero-3-phosphocholine) or DOPC (dioleoyl-sn-glycero-3-phosphocholine) at different temperatures. The flipper probes in DPPC, but not in DOPC, showed a red

• shift of the excitation maximum while emitting the same wavelength. The important difference between these two types of vesicles is their respective membrane phase: LUVs of DPPC undergo a gel to liquid crystalline phase change at the main transition temperature Tm of 41 °C, while LUVs of DOPC remain

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• -C18pPhC18-PC is partially miscible with saturated phosphatidylcholines; however, closed lipid vesicles with an increased thermal stability were not found. Instead, bilayer fragments and disk-like aggregates are formed. Keywords: aggregation behaviour; bolaamphiphiles; bolalipids; membrane lipids; mixing

• ., DPPC did not result in the formation of stabilized lipid vesicles and elongated micelles as well as bilayer fragments were found instead. We have now synthesized a bolalipid with phenyl modification and a slightly longer alkyl chain, PC-C18pPhC18-PC (Figure 1), to investigate a possible chain length

• unmodified bolalipids, such as PC-C32-PC, could not be incorporated into bilayers of DMPC or POPC [28]. In contrast, bolalipids with an alkyl chain modification, e.g., PC-C17pPhC17-PC, were partially miscible with DPPC and DSPC. But, closed lipid vesicles (liposomes) and a pronounced stabilization of the

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• fluorescence assay, which determines the permeation of dithionite ion across membranes (see Experimental, [18][27]). The rate constants of dithionite permeation in large unilamellar vesicles (LUVs) of varying lipid composition are shown in Figure 3 revealing that the rate constants of cholesterol-containing

• vesicles were lower than those of pure POPC LUVs. It is well-known that this sterol decreases the permeability toward polar molecules [28]. The rate constants in the presence of hydroxycholesterols were similar (24R-HC, 24S-HC) or even higher (27-HC) compared to those of pure POPC membranes indicating that

• these sterols are not able to seal a phospholipid membrane like endogenous cholesterol. Influence of hydroxycholesterols on the formation of lateral domains in giant unilamellar vesicles (GUVs) GUVs were prepared consisting of DOPC, PSM, and cholesterol at a molar ratio of 1:1:1. This lipid mixture is

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• mononucleotides [22][28][29]. Because the resulting polymers can be encapsulated in lipid vesicles, it has been proposed that the resulting protocells are candidates for combinatorial selection and the first steps of evolution [30]. Conclusion From the above discussion, alternative conjectures have been published

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• /lysosomal vesicles. The fluorescence of the energy donors, D1, D2 and D4 (Figure 2, left column), as well as the fluorescence of the energy acceptors, D5 and D8 (Figure 2, middle column), could be detected showing that fluorescence energy was transferred from the donor to the acceptor in the respective FRET

• pairs in the endosomal vesicles. This suggested that the DNA duplexes were still intact after transfection into cells. Conclusion The phosphoramidite 7 bearing the arabino-configured analog of uridine 2 that is additionally propargylated at the 2’-position was easily synthesized from commercially

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• phosphatidylcholine (SOPC) or SOPC/cholesterol. In the steady state under such conditions where a negligible fraction of the sterol is bound to CD (i.e., in the presence of submillimolar concentrations), β- and γ-CDs accelerate considerably the rate of cholesterol transfer between lipid vesicles (63- and 64-fold

• affinity with sphingolipids than with other membrane phospholipids. As extension of this work, Huang and London highlighted the possibility of preparing asymmetric vesicles during the exchange of membrane lipids between different vesicles by selective inclusion of phospholipids and/or cholesterol into the

• erythrocytes with Me-β-CD [122]. The results show that the rate of efflux is approximately three orders of magnitude higher than the cholesterol transfer from cells to synthetic vesicles. Therefore, Me-β-CDs are very efficient to extract large amounts of membrane cholesterol at a very high rate. CDs can also

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• leads to aggregation and inactivation under physiological conditions, causing a reduced production of reactive oxygen species [26]. To overcome this drawback, we considered to immobilize the squaraines onto a platform that provides spatial separation (Figure 1). Our platforms of choice are vesicles self

• side can be synthesized in a simple and straightforward three step synthesis [27][30]. Cyclodextrin vesicles (CDVs) can be easily prepared by sonication or extrusion in aqueous solution. CDVs have the unique possibility of versatile surface decoration by the simple addition of guest molecules to the

• applications when a well-known PS, phthalocyanine, was used to decorate the cyclodextrin vesicles [37][38]. The immobilization led to an increased photoactivity of the phthalocyanines due to suppression of aggregation and inactivation of the PS at the surface of the CDVs. In this contribution we show that

Potent triazine-based dehydrocondensing reagents substituted by an amido group

• Munetaka Kunishima,
• Daiki Kato,
• Nobu Kimura,
• Masanori Kitamura,
• Kohei Yamada and
• Kazuhito Hioki

Beilstein J. Org. Chem. 2016, 12, 1897–1903, doi:10.3762/bjoc.12.179

• ], a crown-ether-based cyclotransferase [8], membrane fusion of small unilamellar vesicles to form giant unilamellar vesicles [9], modular methods for the affinity labeling of targeting proteins [10][11][12], and reaction acceleration on micelle interfaces [13][14]. Thus, various types of molecular

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• Supramolecular Chemistry was through the self-assembly of phospholipid membranes to form vesicles for which we were developing unimolecular and self-assembling transporter molecules. The next stage of my development as a scientist was in Japan with Seiji Shinkai where in a “Eureka” moment, the boronic acid

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• modulates the formation of micelles, vesicles, nanospheres (or dense aggregates), and nanocapsules [1]. In particular, non-ionic aCD obtained from β-CD modified with hydrophobic thioalkyl chains (H groups in the following) at the primary rim and short polar PEG oligomers (P groups) at the secondary rim form

• micelles and micellar clusters that are increasingly dispersible in water when functionalized with thioalkyl C2 or C6 chains [23][24] (see Scheme 1), or vesicles with C12 or C16 chains, respectively [17][22]. Potential applications of non-ionic aCD as anticancer and antiviral drug nanocarriers were

• also in solutions these factors are crucial in driving the nucleation and then the large-scale aggregation, inducing the observed arrangements of micelles and/or vesicles and/or nanospheres. It is in general very difficult to model and understand at the atomistic level these events, but theoretical

Size-controlled and redox-responsive supramolecular nanoparticles

• Raquel Mejia-Ariza,
• Gavin A. Kronig and
• Jurriaan Huskens

Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260

• electrochemistry [18] or by adding an oxidizing agent [19]. Different studies have employed this concept to form redox-responsive systems applied, for example, in self-healing materials [19], polymeric hydrogels [20][21], voltage-responsive vesicles [22], ultrasentive enzyme sensors [23], and as a plasma membrane