Controlling molecular shuttling in a rotaxane with weak ring recognition sites.

We describe a rotaxane molecular shuttle encompassing triazolium and tertiary ammonium units as weak recognition sites for the ring. Such a design, which differs from that of typical controllable rotaxanes, allows the precise tuning of the ring distribution among the two sites - i.e., the coconformational equilibrium - by changing the solvent polarity or the nature of the counteranions. Shuttling of the ring between the two stations can also be toggled by acid-base stimuli. Such an approach is paradigmatic to obtain rotaxanes that can sense environmental changes and transduce them into a coconformational response and opens avenues for novel applications in sensing and stimuli-responsive materials.

Photoactivated Artificial Molecular Motors.

Accurate control of long-range motion at the molecular scale holds great potential for the development of ground-breaking applications in energy storage and bionanotechnology. The past decade has seen tremendous development in this area, with a focus on the directional operation away from thermal equilibrium, giving rise to tailored man-made molecular motors. As light is a highly tunable, controllable, clean, and renewable source of energy, photochemical processes are appealing to activate molecular motors. Nonetheless, the successful operation of molecular motors fueled by light is a highly challenging task, which requires a judicious coupling of thermal and photoinduced reactions. In this paper, we focus on the key aspects of light-driven artificial molecular motors with the aid of recent examples. A critical assessment of the criteria for the design, operation, and technological potential of such systems is provided, along with a perspective view on future advances in this exciting research area.

Acidochromism of donor-acceptor Stenhouse adducts in organic solvent.

First generation DASA derivatives can be reversibly isomerized from the coloured, open form to the colourless, closed isomer upon protonation, thus behaving as acidochromic compounds in halogenated organic solvent.

Kinetic and energetic insights into the dissipative non-equilibrium operation of an autonomous light-powered supramolecular pump.

Natural and artificial autonomous molecular machines operate by constantly dissipating energy coming from an external source to maintain a non-equilibrium state. Quantitative thermodynamic characterization of these dissipative states is highly challenging as they exist only as long as energy is provided. Here we report on the detailed physicochemical characterization of the dissipative operation of a supramolecular pump. The pump transduces light energy into chemical energy by bringing self-assembly reactions to non-equilibrium steady states. The composition of the system under light irradiation was followed in real time by 1H NMR for four different irradiation intensities. The experimental composition and photon flow were then fed into a theoretical model describing the non-equilibrium dissipation and the energy storage at the steady state. We quantitatively probed the relationship between the light energy input and the deviation of the dissipative state from thermodynamic equilibrium in this artificial system. Our results provide a testing ground for newly developed theoretical models for photoactivated artificial molecular machines operating away from thermodynamic equilibrium.

Cyst of the canal of Nuck: an atypical course with cyclic changing of size.

As the canal of Nuck normally obliterates before birth, a patent canal is a rare anatomic variant in adult women analogue to the patent processus vaginalis in men. In a patent canal of Nuck, pathologies such as hernias and cyst can build within time. Such cysts themselves are so uncommon that they are mostly described in case reports. Normally, cysts of the canal of Nuck present as a consistent, inguinal swelling with or without pain. Interestingly, in our case, the painful swelling was cyclic changing from the size of a plum to being clinically undetectable within the course of a day. To the best of our knowledge, this is the first description of such an unusual course. The cyst was removed operatively via an open approach. The spasms declined shortly after the operation. At 1 year postoperatively, the patient was still asymptomatic.

Stereodynamics of E/Z isomerization in rotaxanes through mechanical shuttling and covalent bond rotation.

The mechanical bond has opened a new world for structural and dynamic stereochemistry, which is still largely underexplored and whose significance for various applications is becoming increasingly evident. We demonstrate that designed rearrangements involving both covalent and mechanical bonds can be integrated in [2]rotaxanes, leading to interesting consequences in terms of E/Z isomerization mechanisms. Two entirely distinct and concomitant stereomutations, pertaining to the same stereogenic element but involving different kinds of linkages within the molecule, are observed and are thoroughly characterized. The rate of the two processes is affected in opposite ways upon changing solvent polarity; such a phenomenon can be used to selectively modify the rate of each motion and adjust the relative contribution of the two mechanisms to the isomerization. Although the movements are not synchronized, an analysis of the intriguing fundamental implications for transition state theory, reaction pathway bifurcation, and microscopic reversibility was triggered by our experimental observations.

Second-Generation Light-Fueled Supramolecular Pump.

We describe the modular design of a pseudorotaxane-based supramolecular pump and its photochemically driven autonomous nonequilibrium operation in a dissipative regime. These properties derive from careful engineering of the energy maxima and minima along the threading coordinate and their light-triggered modulation. Unlike its precursor, this second-generation system is amenable to functionalization for integration into more complex devices.

Artificial Supramolecular Pumps Powered by Light.

Invited for the cover of this issue is Alberto Credi and co-workers at the University of Bologna and National Research Council, Bologna, Italy. The image represents the photostationary non-equilibrium operation of supramolecular pumps as a hydraulic circuit in which water flows between reservoirs. Read the full text of the article at 10.1002/chem.202101163.

Artificial Supramolecular Pumps Powered by Light.

The development of artificial nanoscale motors that can use energy from a source to perform tasks requires systems capable of performing directionally controlled molecular movements and operating away from chemical equilibrium. Here, the design, synthesis and properties of pseudorotaxanes are described, in which a photon input triggers the unidirectional motion of a macrocyclic ring with respect to a non-symmetric molecular axle. The photoinduced energy ratcheting at the basis of the pumping mechanism is validated by measuring the relevant thermodynamic and kinetic parameters. Owing to the photochemical behavior of the azobenzene moiety embedded in the axle, the pump can repeat its operation cycle autonomously under continuous illumination. NMR spectroscopy was used to observe the dissipative non-equilibrium state generated in situ by light irradiation. We also show that fine changes in the axle structure lead to an improvement in the performance of the motor. Such results highlight the modularity and versatility of this minimalist pump design, which provides facile access to dynamic systems that operate under photoinduced non-equilibrium regimes.

Precision Molecular Threading/Dethreading.

The general principles guiding the design of molecular machines based on interlocked structures are well known. Nonetheless, the identification of suitable molecular components for a precise tuning of the energetic parameters that determine the mechanical link is still challenging. Indeed, what are the reasons of the "all-or-nothing" effect, which turns a molecular "speed-bump" into a stopper in pseudorotaxane-based architectures? Here we investigate the threading and dethreading processes for a representative class of molecular components, based on symmetric dibenzylammonium axles and dibenzo[24]crown-8 ether, with a joint experimental-computational strategy. From the analysis of quantitative data and an atomistic insight, we derive simple rules correlating the kinetic behaviour with the substitution pattern, and provide rational guidelines for the design of modules to be integrated in molecular switches and motors with sophisticated dynamic features.

Photoactivated Artificial Molecular Machines that Can Perform Tasks.

Research on artificial photoactivated molecular machines has moved in recent years from a basic scientific endeavor toward a more applicative effort. Nowadays, the prospect of reproducing the operation of natural nanomachines with artificial counterparts is no longer a dream but a concrete possibility. The progress toward the construction of molecular-machine-based devices and materials in which light irradiation results in the execution of a task as a result of nanoscale movements is illustrated here. After a brief description of a few basic types of photoactivated molecular machines, significant examples of their exploitation to perform predetermined functions are presented. These include switchable catalysts, nanoactuators that interact with cellular membranes, transporters of small molecular cargos, and active joints capable of mechanically coupling molecular-scale movements. Investigations aimed at harnessing the collective operation of a multitude of molecular machines organized in arrays to perform tasks at the microscale and macroscale in hard and soft materials are also reviewed. Surfaces, gels, liquid crystals, polymers, and self-assembled nanostructures are described wherein the nanoscale movement of embedded molecular machines is amplified, allowing the realization of muscle-like actuators, microfluidic devices, and polymeric materials for light energy transduction and storage.

Oligoprolines guide the self-assembly of quaterthiophenes.

Control over the molecular organization of π-conjugated oligothiophenes into different types of supramolecular assemblies is key to their use in organic electronics but difficult to achieve as these chromophores have a pronounced tendency to aggregate. Herein we show that oligoprolines, which do not self-assemble on their own, control the self-assembly of quaterthiophenes. Spectroscopic, microscopic, and diffraction studies with quaterthiophene-oligoproline conjugates revealed the formation of mono- or double-layered sheets or, alternatively, helically twisted ribbons - depending on the length of the oligoproline. The dimensions of the nanoscopic objects, which extend into the micrometer regime, correlate with the molecular dimensions of the quaterthiophene-oligoproline building blocks.

Chemical On/Off Switching of Mechanically Planar Chirality and Chiral Anion Recognition in a [2]Rotaxane Molecular Shuttle.

We exploit a reversible acid-base triggered molecular shuttling process to switch an appropriately designed rotaxane between prochiral and mechanically planar chiral forms. The mechanically planar enantiomers and their interconversion, arising from ring shuttling, have been characterized by NMR spectroscopy. We also show that the supramolecular interaction of the positively charged rotaxane with optically active anions causes an imbalance in the population of the two enantiomeric coconformations. This result represents an unprecedented example of chiral molecular recognition and can disclose innovative approaches to enantioselective sensing and catalysis.

Positional Isomers of Chromophore-Peptide Conjugates Self-Assemble into Different Morphologies.

Ordering π-systems into defined supramolecular structures is important for the development of organic functional materials. In recent years, peptides with defined secondary structures and/or self-assembly properties were introduced as powerful tools to order peptide-chromophore conjugates into different morphologies. This work explores whether or not the directionality of peptides can be used to control the self-assembly. The position of the π-system in conjugates between oligoprolines and perylene monoimide (PMI) chromophores was varied by attaching the PMI moiety to the second-to-last residue from the C- and N-termini, respectively. Microscopic and diffraction analysis revealed that the positional isomers form distinctly different supramolecular architectures that extend into the micrometer regime. NMR spectroscopic studies in solution phase allowed correlation of the self-assembly properties with markedly different conformational preferences of the isomeric building blocks. These insights enabled the design of building blocks with predictable self-assembly properties. Thus, the directionality of peptides offers exciting opportunities for controlling the self-assembly and electronic properties of π-systems.

Photoactive Molecular-Based Devices, Machines and Materials: Recent Advances.

Molecular and supramolecular-based systems and materials that can perform predetermined functions in response to light stimulation have been extensively studied in the past three decades. Their investigation continues to be a highly stimulating topic of chemical research, not only because of the inherent scientific value related to a bottom-up approach to functional nanostructures, but also for the prospective applications in diverse fields of technology and medicine. Light is an important tool in this context, as it can be conveniently used both for supplying energy to the system and for probing its states and transformations. In this microreview we recall some basic aspects of light-induced processes in (supra)molecular assemblies, and discuss their exploitation to implement novel functionalities with nanostructured devices, machines and materials. To this aim we illustrate a few examples from our own recent work, which are meant to illustrate the trends of current research in the field.

A triaxial supramolecular weave.

Despite recent advances in the synthesis of increasingly complex topologies at the molecular level, nano- and microscopic weaves have remained difficult to achieve. Only a few diaxial molecular weaves exist-these were achieved by templation with metals. Here, we present an extended triaxial supramolecular weave that consists of self-assembled organic threads. Each thread is formed by the self-assembly of a building block comprising a rigid oligoproline segment with two perylene-monoimide chromophores spaced at 18 Å. Upon π stacking of the chromophores, threads form that feature alternating up- and down-facing voids at regular distances. These voids accommodate incoming building blocks and establish crossing points through CH-π interactions on further assembly of the threads into a triaxial woven superstructure. The resulting micrometre-scale supramolecular weave proved to be more robust than non-woven self-assemblies of the same building block. The uniform hexagonal pores of the interwoven network were able to host iridium nanoparticles, which may be of interest for practical applications.

Peptide mediated formation of noble metal nanoparticles-controlling size and spatial arrangement.

Over the past two decades, peptides have expanded the toolbox of additives for the preparation of noble metal nanoparticles. Their functional and structural modularity and accompanying molecular recognition and self-assembly properties offer unique opportunities for the controlled formation of NPs. Within this review, we highlight recent examples for the use of peptides to control a) the size and shape of NPs and b) the spatial arrangement of NPs. The article focuses on examples where the peptides are directly involved in the bottom-up synthesis of the noble metal NPs.

Size-Controlled Formation of Noble-Metal Nanoparticles in Aqueous Solution with a Thiol-Free Tripeptide.

A combinatorial screening revealed the peptide H-His-d-Leu-d-Asp-NH2 (1) as an additive for the generation of monodisperse, water-soluble palladium nanoparticles with average diameters of 3 nm and stabilities of over 9 months. The tripeptide proved to be also applicable for the size-controlled formation of other noble-metal nanoparticles (Pt and Au). Studies with close analogues of peptide 1 revealed a specific role of each of the three amino acids for the formation and stabilization of the nanoparticles. These data combined with microscopic and spectroscopic analyses provided insight into the structure of the self-assembled peptidic monolayer around the metal core. The results open interesting prospects for the development of functionalized metal nanoparticles.

Intradermal therapy (mesotherapy) for the treatment of acute pain in carpal tunnel syndrome: a preliminary study.

BACKGROUND: The carpal tunnel syndrome (CTS) is the most common cause of severe hand pain. In this study we treated acute pain in CTS patients by means of local intradermal injections of anti-inflammatory drugs (mesotherapy). METHODS: In twenty-five patients (forty-five hands), CTS diagnosis was confirmed by clinical and neurophysiological examination prior to mesotherapy. A mixture containing lidocaine 10 mg, ketoprophen lysine-acetylsalycilate 80 mg, xantinol nicotinate 100 mg, cyanocobalamine 1,000 mcg plus injectable water was used. Sites of injection were three parallel lines above the transverse carpal ligament and two v-shaped lines, one at the base of the thenar eminence, and the other at the base of the hypothenar eminence. RESULTS: The day after the treatment, all but four patients reported a significant reduction in pain and paresthesias. After 12 months, 17 patients had a complete pain relief, eight patients reported recurrence of pain and sensory symptoms and four out of them underwent surgical treatment. CONCLUSIONS: With the obvious limits of a small-size open-label study, our results suggest that mesotherapy can temporary relieve pain and paresthesias in most CTS patients and in some cases its effect seems to be long-lasting. Further controlled studies are needed to confirm our preliminary findings and to compare mesotherapy to conventional approaches for the treatment of CTS.

Severe and polytraumatic injuries among recreational skiers and snowboarders: incidence, demographics and injury patterns in South Tyrol.

BACKGROUND: Alpine skiing and snowboarding are popular winter sports. The practice of these sports is related to traumatic injuries, some of which are severe and/or life threatening. OBJECTIVES: To identify the incidence, injury patterns and associated risk factors of severe and polytraumatic injuries in South Tyrol. MATERIALS AND METHODS: During four consecutive winter seasons (2001-2005), data of every patient referred to our emergency department (Bolzano-Bozen) after a skiing or snowboarding accident were collected. One hundred and five patients with an Injury Severity Score of 16 or higher were identified (90 skiers, 15 snowboarders). Statistical descriptive analyses were carried out by producing frequency tables. Chi-square test was performed to verify possible association between injury severity and type of sport. Risk factors for severe injuries were evaluated using logistic regression with robust variance estimators. RESULTS: Traumatic brain injury was the most common injury observed (51 cases), followed by vertebral injury (45 cases); 63% of the patients reported two or more associated injuries. We observed significant associations between severe spine injuries and the following risk factors: snowboarders who reported more severe injuries than skiers [odds ratio=5.89, 95% confidence interval (CI)=1.31, 26.44], age classes of 40-50 years and over 60 years showed an OR of 8.10 (95% CI=1.87, 35.06) and 5.16 (95% CI=1.27, 21.01), respectively, with respect to age class (20-40 years). CONCLUSION: Severe traumatic injuries occur among skiers and snowboarders, and preventive measures such as the use of helmets and educational programs, are necessary.