Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• aqueous environments, water solubility is also essential [16][17][18]. A promising approach is the embedment of the GH-type catalyst into well-defined protein scaffolds [19]. The combination of an engineered protein with a synthetic metal catalyst leads to artificial metalloproteins [20][21][22][23]. In

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• -cleavable linker. A polyethylene glycol (PEG) linker was selected as PEG linkers demonstrate enhanced water solubility in comparison to alkyl chain linkers. We then had to make a decision on the position of attachment for the PEG linker to compound 1. For siderophore conjugates, it is crucial that the

• phenothiazine 5 was isolated after removal of the Boc protecting group in TFA. Initial attempts at aqueous work-up conditions to isolate the free base resulted in lower isolated yields of 5 due to its high water solubility, and it was decided 5 would be progressed further as the TFA salt avoiding aqueous work

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• guests exhibit a significant fluorescence intensity enhancement and the intensity is strong enough to be distinguished by the naked eye. The easy accessibility, good water-solubility and nice binding properties make 2,2’-CBP4 be applicable in the biomedical field, for example, chemical sensors, drug

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ][65][66]. The effect of the donor substituent on the emission quenching was supported by the strong increase of the emission quantum yield of 2c upon protonation of the amino group, that is, by the transformation of the donor to an acceptor substituent (Figure 5) [34]. Considering the water solubility

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• bases including pyridine, Et3N, KOH, K2CO3 and Cs2CO3 were then evaluated. All except Et3N provided the expected biaryl 23a in comparable and excellent yields (Table 2, entries 4–8). The poor performance of Et3N as base in the reaction could be due to its low water solubility. KOH as a common laboratory

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

• moderate water solubility and peptide-like folding properties [9] are hurdles for their biological application. As an alternative strategy, the (deoxy)ribose part of the backbone has been retained and only some of the internucleotide phosphate diesters have been selectively replaced by electroneutral

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• low water-solubility and stability led to the formulation of various new analogs with the same mechanism of action. The two most progressed analogs of CPT are topotecan and irinotecan. Topotecan (hycamtin) has been approved by the FDA for the treatment of ovarian and cervical cancer, as also small

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• solvents in organic synthesis. The reaction in water as a solvent provided moderate yields (procedures B1 and B2), but the subsequent scale-up of these reactions could be favorable on using intermediates with better water solubility. The best reaction yields for TO-7Cl were obtained on using procedure C1

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -trifluoromethylated analogues in the presence of trimethylphosphine, with moderate to excellent yields (Scheme 33). The higher nucleophilicity of trimethylphosphine versus triphenylphosphine and the water solubility of trimethylphosphine oxide byproducts were essential elements in choosing the reducing agent. Both

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• sometimes inconvenient in terms of membrane permeability, water solubility, and inhibition of inherent interactions between the probe molecule and the target enzyme. We have developed a new OFF–ON probe with a small fluorescent core unit. The same approach was recently used to produce a fluorophore for a

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• suppressing its aggregation property. It is also necessary to improve the water solubility of the lipophilic phthalocyanine in order to increase its biocompatibility [88][89]. One frequent method to increase the water solubility of phthalocyanine involves the combination of a biomolecule such as a sugar [90

• likely to occur with a long residence time of the compound in blood. The residence time in blood is prolonged by increasing the water solubility of the drug. An ideal PDT drug would improve the water solubility of TFEO-Pc. In 2006, TFEO-ZnPcs were conjugated with deoxyribonucleosides 16 and 17 for

• possible use in PDT [99]. The deoxyribonucleoside unit is expected to enhance the water solubility of the phthalocyanine, facilitating its incorporation into cancer cells which undergo active cell division. These TFEO-ZnPc/deoxyribonucleoside hybrids were synthesized from unsymmetrical A3B-type TFEO-ZnPc

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• diseases and having only negligible side effects, low water solubility and fast degradation limit their potential medical application to this day [7]. The formation of the curcumin structure motif takes place by a base catalysed aldol condensation between the corresponding aldehyde and 2,4-pentanedione. To

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• pharmacokinetic properties of the guest molecule, such as water solubility, bioavailability and stability [6][7]. In particular, many important drugs in cancer treatment are often toxic and/or sparingly soluble or even insoluble in water. Among other methods, reversible derivatization of these drugs into CD

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• incorporated in a broad diversity of molecules and polymers to introduce specific properties including water solubility, coordination or supramolecular properties. Several books, book chapters or reviews have been focused on the construction of the P–C bond [1], on the description of the different classes of

• this property was used to increase the water solubility of organic compounds [13][14], polymers [15][16] or ligands for coordination chemistry [17]. It must be noted that for similar compounds, that only differ by the replacement of a carboxylic acid group with a phosphonic acid moiety, the log POW

• water soluble catalysts [21], or to improve the water solubility of drug-chelate supramolecular assemblies (e.g., calixarene) [22][23]. The water solubility of phosphonic acid is strongly improved when the phosphonic acid is deprotonated (basic media). It is not rare to observe, when preparing NMR tubes

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• -soluble ligated palladium catalysts. This approach not only enhances the water solubility of the catalyst, but also facilitates the recovery of the catalyst by separating the aqueous phase and subsequently for the potential reuse of catalyst [17]. Initially, such catalysts have been obtained through

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• spiropyran-modified agarose gel [14][15] and the creation of light-responsive nanopores through modification of natural channel proteins [16]. Furthermore, addition of an N-alkylcarboxylate moiety is a common tactic used to enhance water solubility of spiropyran derivatives [6]. Spiropyran–metal cation

One-pot synthesis of block-copolyrotaxanes through controlled rotaxa-polymerization

• Jessica Hilschmann,
• Gerhard Wenz and
• Gergely Kali

Beilstein J. Org. Chem. 2017, 13, 1310–1315, doi:10.3762/bjoc.13.127

• hydrophobic interaction, as the driving force of complex formation, the threading of the CDs is only achievable in aqueous solution, but the hydrogen bonds between the hydroxy groups impede the water solubility of the products. Thus, the stoppering reaction is mostly limited to organic solutes, in which

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• first group appear at low elution time (from 2 to 4 min) and has increased water solubility, suggesting the presence of unmodified CD and CDs with low substitution degree. The second group, eluted from 9 to 18 minutes, contained modified CDs and PLA oligomers. The overlaid LC chromatograms for crude α

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

• of sterols to and from membranes, this can be principally realized via vesicular traffic or via monomeric transfer. The latter mechanism requires the presence of donors and acceptors, respectively, due to the low water solubility of sterols. Nevertheless, the import and export of cholesterol is

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• traditional semiconductor quantum dots (QDs). Particularly in the areas of live imaging and drug delivery, due to their water solubility, low toxicity and photo- and chemical stability. Carbohydrates are readily available chiral biomolecules in nature which offer an attractive and cheap starting material from

• , chemical sensing, biosensing, bioimaging and nanomedicine, due to their unique tuneable photoluminescence (PL) properties, chemical inertness, high water solubility, ease and low cost fabrication and more importantly, low toxicity profiles. The latter makes these fluorescent nanomaterials attractive for a

• due to their high water solubility, low-carbonisation temperatures, low cost and typically inherently lack toxicity. With all these options available to tune the synthesis of CDs, it is no surprise that researchers have already began to see the benefits of carbohydrates when considering the synthesis

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• , 4a was modified with 2-(2-hydroxyethoxy)ethyl (HEE) groups to impart water solubility, which was necessary for in vitro cellular experiments (Scheme 3) [32][33]. Then, the terminal benzylazide groups of HEE-PRX-Bn-N3 (6) were modified with dibenzylcyclooctyne (DBCO)-conjugated fluorescent molecules

• click reactions, including ligand molecules for active targeting, radioactive molecules for in vivo imaging, hydrophobic polymers for the surface immobilization of PRXs, and hydrophilic polymers for acquiring water solubility. Accordingly, the azide group-terminated end-reactive 4a and 4b are expected

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

• Loic Leclercq Univ. Lille, CNRS, ENSCL, UMR 8181 – UCCS - Equipe CÏSCO, F-59000 Lille, France 10.3762/bjoc.12.261 Abstract In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs

• , the structural elucidation of the three natural CDs, α-, β-, and γ-CDs composed of 6-, 7-, and 8-membered α-D-glucopyranoses linked by α-1,4 glycosidic bonds, allowed the development and the rational study of their encapsulation properties [6][7]. As their water solubility differs significantly, a

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

• double bonds, the complex can react further to produce 3-HBT (3-hexylbenzo[d]thiazol-2(3H)-one). The photogenerated oxidation products can then induce radical-chain reactions with the surrounding cell material, leading to cell toxicity. However, like most PS, squaraines have poor water solubility, which