Modifying the Catalytic Activity of Lipopeptide Assemblies with Nucleobases.

Biohybrid catalysts that operate in aqueous media are intriguing for systems chemistry. In this paper, we investigate whether control over the self-assembly of biohybrid catalysts can tune their properties. As a model, we use the catalytic activity of functional hybrid molecules consisting of a catalytic H-dPro-Pro-Glu tripeptide, derivatized with fatty acid and nucleobase moieties. This combination of simple biological components merged the catalytic properties of the peptide with the self-assembly of the lipid, and the structural ordering of the nucleobases. The biomolecule hybrids self-assemble in aqueous media into fibrillar assemblies and catalyze the reaction between butanal and nitrostyrene. The interactions between the nucleobases enhanced the order of the supramolecular structures and affected their catalytic activity and stereoselectivity. The results point to the significant control and ordering that nucleobases can provide in the self-assembly of biologically inspired supramolecular catalysts.

Catalytic templated length-controlled oligomerization.

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.

Chiral Recognition of Amino Acid Esters in Organic Solvents Using a Glucose-Based Receptor.

Due to the chemical and biological relevance of amino acids, efficient methods for the recognition and separation of their enantiomers are highly sought after. Chiral receptors based on extended molecular scaffolds are typically employed for this purpose. These receptors are often effective only in specific environments and towards a narrow scope of amino acid guests. Recently we reported a simple, glucose-based macrocycle capable of enantioselective binding of a broad range of amino acid methyl esters in water. Herein we demonstrate that the same receptor can be used for chiral recognition of amino acid esters in organic solvents. We show that the binding affinity and selectivity of the receptor are highly dependent on the coordinating strength of the solvent. An in-depth analysis of the receptor's conformation and its interactions with amino acid methyl esters allowed us to propose a binding mode of amino acids to the receptor in CDCl3. The binding modes in CDCl3 and D2O were then compared, highlighting the main interactions responsible for binding affinity and selectivity in each solvent. We envision that the insight provided by this study will facilitate the development of further amino acid receptors based on monosaccharides with improved binding affinities and both enantio- as well as chemoselectivities.

Organic Molecular Weaves.

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.

Shape Persistence of Polyproline†II Helical Oligoprolines.

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.

A crystal structure of an oligoproline PPII-helix, at last.

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.

Exploring the activation modes of a rotaxane-based switchable organocatalyst.

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.

Efficient assembly of threaded molecular machines for sequence-specific synthesis.

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.

Synthetic molecular walkers.

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.

Artificial Intelligence, or just statistics done different?

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.

Chiral recognition of amino-acid esters by a glucose-derived macrocyclic receptor.

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.

A 10-Year Follow-up on Arthroscopic Medial Plica Syndrome Treatments with Special Reference to Related Cartilage Injuries.

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.

Resveratrol in the treatment of neuroblastoma: a review.

Resveratrol, polyphenol naturally occurring in grapes or nuts, has anti-cancer properties in the treatment of neuroblastoma - the most common childhood solid tumor. It affects cancer cells by increasing apoptosis, inducing cell necrosis and reducing tumor mass. Mechanism of action - (1) converting procaspases, mainly procaspases three and nine into active forms - caspases, (2) blocking kinases, and also (3) leading the cell to the S-cell cycle, where it is most effective while increasing the concentration of cyclin E and lowering the concentration of p21 protein. In vitro, as well as, rodent animal models studies are available and show promising results. Therapeutic doses, currently within 10-100 µmol/L, are also being tested, as well as other forms of resveratrol, such as its trans-4,4'-dihydroxystilbene analog and polyphenol lipoconjugates. In our review, we presented the known molecular mechanisms of polyphenol anti-tumor activity against neuroblastoma and discussed the studies confirming its effectiveness.

Chiral recognition of alpha-phenylethylamine by sucrose-based macrocyclic receptors.

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

Synthesis and complexation properties towards the ammonium cation of aza-coronand analogues containing sucrose.

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.