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As interest in AI in medicine grows, so too does the need for education on the topic. Despite the technology itself being so close, our understanding of the essence of how it works remains remote. A greater, more judicious acceptance of AI tools can be fostered in medicine by a broader appreciation of what the technology can and cannot do.

Templated synthesis is an intriguing strategy for the length-controlled synthesis of oligomers. Traditionally, such reactions require stoichiometric amounts of the template with respect to the product. Recently we reported catalytic macrocyclic templates that promote oligomerization of a small molecule substrate with a remarkable degree of length control. Herein we present our efforts toward creating linear templates for catalytic length-controlled oligomer synthesis., Faraday Discussions, ISSN:1359-6640, ISSN:1364-5498

We report a glucose-based crown ether capable of chiral recognition of a wide range of amino-acid methyl esters in aqueous environments. The enantioselectivities towards amino-acids with extended hydrophobic side chains displayed by the glucose-derived macrocycle are among the highest observed for small molecule synthetic receptors to date.

Objective The aim of this study was to evaluate the factors that can affect long-term results of arthroscopic resection of medial synovial plica of the knee. Design A total of 52 knees in 50 consecutive patients with medial plica syndrome (MPS) were enrolled to prospective study. Preoperatively the age, gender, level of activity, symptoms’ duration, Lysholm knee scoring scale (LKSS), Q angle, range of motion (ROM), and quadriceps output torque (QOT) were recorded. The plica was then arthroscopically excised while plica morphological type and cartilage lesions (International Cartilage Repair Society [ICRS] classification) were registered. The postoperative evaluation was done after 1 month, 3 months, 6 months, 3 years, and 10 years. The final assessment after 10 years covered LKSS, ROM, QOT, and was enriched with functional tests: the single leg squat test (SLS), the modified Ober test (MO), and the manual palpation of the vastus medialis obliquus (VMO). Results The mean LKSS increased from 52 (15-85, SD 16.479) preoperative to 80 (48-100, SD 15.711) at final follow-up examination. A significant negative correlation was found between LKSS and the patients’ age. Cartilage lesions higher than ICRS 1 significantly decreased the final LKSS. Results were significantly better in the subgroups with normal outcome of functional tests. Conclusions Clinical results of arthroscopic plica resection are better in patients without coexisting cartilage lesions. Poor neuromuscular control may contribute to abnormal patella tracking, leading to both medial plica irritation and further cartilage deterioration.

Weaving of organic compounds on the molecular level is an intriguing challenge and promises to provide materials that combine high elasticity with strength and fracture toughness. Yet, the formation of crossing points between molecular threads in defined and regular distances to create an interwoven network is not trivial. To date, only a few examples of wholly organic weaves have been reported. Within this review we present the different strategies that enabled their formation and highlight the structural features of the obtained nanostructured materials. We expect these pioneering studies to pave the way to many more organic molecular weaves with more and more sophisticated topologies and exquisite mechanical properties.

The activation mode of a rotaxane-based organocatalyst with both secondary amine and squaramide catalytic units can be switched with acid or base. The macrocycle blocks whichever of the catalytic sites it is positioned over. The switchable rotaxane catalyst generates different products from a mixture of three building blocks according to the location of the macrocyclic ring in the rotaxane.

The first crystal structure of an oligoproline adopting an all-trans polyproline II (PPII) helix is presented. The high-resolution structure provides detailed insight into the dimensions and conformational properties of oligoprolines that are important for, e.g., their use as "molecular rulers" and "molecular scaffolds". The structure also showed that the amides interact with each other within a PPII helix and that water is not necessary for PPII helicity.

We report on an improved strategy for the preparation of artificial molecular machines that can pick up and assemble reactive groups in sequence by traveling along a track. In the new approach a preformed rotaxane synthon is attached to the end of an otherwise fully formed strand of building blocks. This "rotaxane-capping" protocol is significantly more efficient than the "final-step-threading" method employed previously and enables the synthesis of threaded molecular machines that operate on extended oligomer, and potentially polymer, tracks. The methodology is exemplified through the preparation of a machine that adds four amino acid building blocks from a strand in sequence, featuring up to 20-membered ring native chemical ligation transition states. © 2014 American Chemical Society.

[263847-08-1] C20H18N4O4 (MW 378.39) InChI = InChI=1S/C20H18N4O4/c21-23-22-12-9-18(19(25)26)24(10-12)20(27)28-11-17-15-7-3-1-5-13(15)14-6-2-4-8-16(14)17/h1-8,12,17-18H,9-11H2,(H,25,26)/t12-,18-/m0/s1 InChIKey = HOPXMBBEYJTPNX-SGTLLEGYSA-N (this building block is an attractive derivative of a common nonproteinogenic amino acid that offers, via the azide group, a conjugation site that is orthogonal to many other functional groups; the presence of the azide group gives the possibility of convenient functionalization and also affects the pyrrolidine the PPII ring conformation, which in turn influences helix stability) Alternate Names: Fmoc-(4S)Azp-OH; Fmoc-(4S)-azidoproline; Fmoc-cis-azidoproline-OH; Fmoc-2S,4S-azidoproline; Fmoc-(cis-4-N3)Pro-OH; Fmoc-cis-N3-Pro-OH. Physical Data: mp 178−181 °C. Solubility: alcohols, THF, CH3CN, DMF, DMSO; sparingly soluble in CHCl3, CH2Cl2. Form Supplied in: white solid. Analysis of Reagent Purity: 1H NMR shows a double set of peaks due to cis and trans conformers around the tertiary carbamate. Preparative Method: Fmoc-(4S)Azp-OH can be obtained from Boc-(4R)Hyp-OMe, which is conveniently synthesized in two steps from trans-4-hydroxy-L-proline (H-(4R)Hyp-OH) by esterification of the carboxylic acid followed by Boc protection of the amino group.1 Stereoselective transformation of the secondary alcohol into an azide can be achieved either by activation of the alcohol using methanesulfonyl chloride followed by nucleophilic substitution with NaN32 or directly using Mitsunobu conditions (DPPA, DEAD, Ph3P).3 Subsequent methyl ester and Boc cleavage followed by Fmoc protection of the amine gives Fmoc-(4S)Azp-OH as a white solid in 74% yield from Boc-(4R)Hyp-OMe.4 Importantly, the synthesis can be executed on a multigram scale. Caution! In the presence of traces of acid, NaN3 forms hydrazoic acid (HN3), which is highly toxic and explosive at room temperature; the syntheses should be carried out in a fume hood behind a protective screen.5 The intermediate material after saponification and Boc cleavage has a high N/C ratio and needs to be handled with care and should not be exposed to heat over prolonged periods of time. Purification: crystallization from EtOH. Column chromatography (SiO2) CH2Cl2:MeOH 9:1. Handling, Storage, and Precautions: the compound is stable over prolonged periods of time (over 2 years) when stored in a cool and dry place in a well-closed container.

ISSN:0018-019X ISSN:1522-2675

Ribosomal Rotaxane? The ribosome is an extraordinarily sophisticated molecular machine, assembling amino acids into proteins based on the precise sequence dictated by messenger RNA. Lewandowski et al. (p. 189 ) have now taken a step toward the preparation of a stripped-down synthetic ribosome analog. Their machine comprises a rotaxane—a ring threaded on a rod—in which the ring bears a pendant thiol that can pluck amino acids off the rod; the terminal nitrogen then wraps around to form a peptide bond and liberate the thiol for further reaction. The system was able to link three amino acids in order from the preassembled rod.

It has been brought to author’s attention that lowest line of subplots in Figure 3 was erroneously swapped with the upper line of subplots in Figure 4. Figure captions in the article are correct for the figures given below. (Figure Presented.).

1′,2,3,3′,4,4′-Hexa-O-benzyl-sucrose was applied in the preparation of sucrose-based macrocycles via a click chemistry route. This was realized by protection of the 6′‒OH with silyl block followed by elongation of the glucose end with the ‒CH2CH2N3 unit. Removal of the silyl block and subsequent propargylation of the released C6′‒OH afforded the corresponding synthon, cyclization of which under the click condition provided the desired macrocycle with the expected 1,4-pattern of substituents at the triazole ring.

Two new routes to derivatives of 2,3,3′,4,4′-penta-O-benzylsucrose with differently protected primary hydroxyl groups were elaborated. One of these compounds, 2,3,3′,4,4′-penta-O-benzyl-6′-O-mesylsucrose, was used in a model synthesis of the 6′-phosphine with sucrose scaffold. Elimination of the mesyloxy- group under the reaction conditions was also noted providing the 5′,6′-unsaturated sucrose derivative.

The material reviewed in this paper covers only the last five years, with emphasis on the most recent results. It will not be comprehensive and will deal only with such transformations of simple sugars (and to some extent disaccharides), which lead to interesting optically pure compounds of (at leas...

The carbanions of (E)- and (Z)-1-chloro-5-(phenylsulfonyl)-pent-2-enes can be considered as vinylogues of γ-chlorocarbanions. Because in these cases intramolecular 1,3-substitution by a SN2′ mechanism leading to vinylcyclopropanes is a relatively slow process these carbanions can be efficiently trapped by active electrophilic reagents such as aldehydes. Subsequent intramolecular SN2′ 1,5-substitution of the aldol anions produced gives vinyl-substituted tetrahydrofurans. Thus, an efficient method for the synthesis of 2,3-disubstituted-5-vinyltetrahydrofurans has been elaborated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Chiral macrocycles containing the sucrose skeleton were prepared by a ‘click chemistry’ route. The substrate for the Huisgen reaction was obtained from sucrose in eight steps. The 1,3-dipolar cycloaddition yielded the intramolecular as well as the C 2 -symmetric macrocycles. Optimization of the reaction conditions allowed the preparation of both types of adducts with high selectivity and in good yields.

Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

Oligoprolines are commonly used as molecular scaffolds. Past studies on the persistence length of their secondary structure, the polyproline II (PPII) helix, and on the fraction of backbone cis amide bonds have provided conflicting results. We resolved this debate by studying a series of spin-labeled proline octadecamers with EPR spectroscopy. Distance distributions between an N-terminal Gd(III) -DOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) label and a nitroxide label at one of five evenly spaced backbone sites allowed us to discriminate between the flexibility of the PPII helix and the cis amide contributions. An upper limit of 2 % cis amide bonds per residue was found in a 7:3 (v/v) water/glycerol mixture, whereas cis amides were not observed in trifluoroethanol. Extrapolation of Monte Carlo models from the glass transition to ambient temperature predicts a persistence length of ≈3-3.5 nm in both solvents. The method is generally applicable to any type of oligomer for which the persistence length is of interest.

Detailed knowledge of the geometry and conformational dynamics of molecules used as molecular scaffolds is crucial for the design of functional compounds based on this architecture. Oligoproline is such a molecular scaffold that adopts in aqueous environments a left-handed helix, the Polyproline II (PPII)-helix [1]. Powder diffraction studies provided in the 1950s valuable low-resolution information about the PPII-helix [2]. They revealed basic parameters e.g., the all-trans configuration of the amide bonds and that every third residue is stacked on top of each other. However, in contrast to crystal structures of collagen and several other proteins with PPII-helical domains, crystallization of an oligoproline in a PPII-helical conformation had remained elusive. Our interest in the use of azidoproline-containing oligoprolines as functionalizable scaffolds [3-6] led us to revisit the crystallization of oligoprolines.

Crown ether analogues with incorporated sucrose unit were prepared by reaction of 1′,2,3,3′,4,4′-hexa-O-benzylsucrose with polyethylene ditosylates in up to 52% yield. Stability constants of their complexes with Li+, Na+, K+, NH4+ were determined by the NMR titration method. The macrocycles were also tested as catalysts in the enantioselective Michael reaction, but with little success (ee up to only 22%). The macrocycle containing nitrogen in the ring was also prepared in good yield. All prepared macrocycles were easily converted into the free sucrose crowns (H2/Pd/C) without destroying the (very labile) glycosidic bond. The crystal structure of the selected receptor was determined.

The reactivity of a rotaxane that acts as an aminocatalyst for the functionalization of carbonyl compounds through HOMO and LUMO activation pathways has been studied. Its catalytic activity is explored for C–C and C–S bond forming reactions through iminium catalysis, in nucleophilic substitutions and additions through enamine intermediates, in Diels–Alder reactions via trienamine catalysis, and in a tandem iminium-ion/enamine reaction. The catalyst can be switched “on” or “off”, effectively controlling the rate of all of these chemical transformations, by the in situ change of the position of the macrocycle between two different binding sites on the rotaxane thread.

Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

In biological systems, molecular motors have been developed to harness Brownian motion and perform specific tasks. Among the cytoskeletal motor proteins, kinesins ensure directional transport of cargoes to the periphery of the cell by taking discrete steps along microtubular tracks. In the past decade there has been an increasing interest in the development of molecules that mimic aspects of the dynamics of biological systems and can became a starting point for the creation of artificial transport systems.To date, both DNA-based and small-molecule walkers have been developed, each taking advantage of the different chemistries available to them. DNA strollers exploit orthogonal base pairing and utilize strand-displacement reactions to control the relative association of the component parts. Small-molecule walkers take advantage of the reversibility of weak noncovalent interactions as well as the robustness of dynamic covalent bonds in order to transport molecular fragments along surfaces and molecular tracks using both diffusional processes and ratchet mechanisms. Here we review both types of synthetic systems, including their designs, dynamics, and how they are being used to perform functions by controlled mechanical motion at the molecular level.

In biological systems, molecular motors have been developed to harness Brownian motion and perform specific tasks. Among the cytoskeletal motor proteins, kinesins ensure directional transport of cargoes to the periphery of the cell by taking discrete steps along microtubular tracks. In the past decade there has been an increasing interest in the development of molecules that mimic aspects of the dynamics of biological systems and can became a starting point for the creation of artificial transport systems.

FRANTIŠEK WEYR (1879-1951): A FORGOTTEN NORMATIVIST Summary František Weyr (1879-1951) was one of the most outstanding adherents of the normative theory of legal science during the inter-war period. His scholarly activity was focused on the basic issues important for normativism, on which he embarked shortly before Hans Kelsen’s, and with no influence from Kelsen (Weyr published his earliest book in 1908). Weyr was one of the founders and the main representative of the Czechoslovak Neo-Kantian Law School, which was composed of his former students, members of the Faculty of Law at the Tomáš Masaryk University in Brno. Members of the Czechoslovak Neo-Kantian Law School engaged in numerous polemics on key normativist issues (e.g. the nature of legal norms). F. Weyr’s work in the philosophy of law made a salient contribution to the turbulent history of Czechoslovakia, exerting an influence from the auspicious years of the independent Second Republic (1918-1938), through the period of the Czech and Moravian Protectorate under Nazi German occupation during the Second World War, to the postwar period under the Communist regime and its miserable demise in 1990. Weyr is appreciated in Czech scholarship for his achievements in the theory of law. Although he was one of the key figures associated with normativism, often compared with his colleague H. Kelsen, his work in scholarship is not well known in the Polish theory of law.

The reactions of 3,4-dichlorophenylmagnesium bromide and 3,5-dichlorophenylmagnesium bromide with B(OEt) 3 and NaBF 4 were studied The corresponding tetraarylborates [(3,4-Cl 2 C 6 H 3 ) 4 B]NH 4 and [(3,5-Cl 2 C 6 H 3 ) 4 B]Na were obtained and characterized. The significant influence of the substituents inductive effect on the reaction course was revealed. NaBF 4 was found to be a valuable boron reagent in the synthesis of tetraarylborates containing highly electronegative substituents. The molecular structure of [(3-CF 3 C 6 H 4 ) 4 B]NH 4 obtained from the reaction of 3-trifluoromethylbromobenzene with NaBF 4 and Mg was determined using X-ray analysis.

1′,2,3,3′,4,4′-Hexa-O-benzyl-sucrose was applied in the preparation of sucrose-based macrocycles via a click chemistry route. This was realized by protection of the 6′‒OH with silyl block followed by elongation of the glucose end with the ‒CH2CH2N3 unit. Removal of the silyl block and subsequent propargylation of the released C6′‒OH afforded the corresponding synthon, cyclization of which under the click condition provided the desired macrocycle with the expected 1,4-pattern of substituents at the triazole ring.

The reaction of penta-O-benzyl sucrose (I) with tert-butyldiphenylsilyl chloride proceeds regioselectively to afford 6′-O-silyl derivative (III), which is used for the synthesis of iodide (VI).

C(2)-Symmetrical chiral macrocycles containing two sucrose units were prepared by an amino acid templated macrocyclization reaction between appropriate sucrose-based linear precursors and ethylenediamine.

Interoperability between collaborative development platforms (forges) in the Open Source Software world is a significant issue. The forges tend to follow the lock-in phenomenon, providing no easy-to-use facilities for migrating projects or their parts between forge platforms. To facilitate the process of cross-forge project migration, the following paper presents an approach of lifting forge data models to the semantic level and applying rule-based mappings for their alignment. The approach also involves Semantic Web Services to handle the process of importing/exporting project metadata from/to Open Source Software forges. Finally, the paper demonstrates the approach on the basis of proof-of-concept implementation exploiting the existing forges and presents the lessons learnt.

Simple chiral aza-crown ethers based on sucrose display high enantioselectivity in complexation of phenylethylammonium chlorides.

1',2,3,3',4,4'-Hexa-O-benzyl-sucrose was converted in good yields into the macrocyclic receptors containing two and three nitrogen atoms in the ring. Their complexation properties towards the ammonium cation were significantly higher than for receptors without any nitrogen atoms in the ring.