The design of molecular systems in which controlled linear and rotary motion can be achieved under the influence of an external signal is a major endeavor toward future nanoscale machinery. In this ...Account we describe the development of molecular switches and the discoveries that culminated in the first light-driven molecular motor. Various chiral optical molecular switches and their use as trigger elements to control organization and functions will be discussed. The construction of the first and second generation molecular motors is presented.
The development of an efficient catalytic system for enantioselective carbon−carbon bond formation by 1,4-addition of organometallic reagents (organolithium, Grignard, and organozinc reagents) to ...enones is a major challenge in organic synthesis. This Account presents the breakthrough realized in this field using chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions. Applications in catalytic routes to cycloalkanones as well as tandem and annulation procedures with excellent enantioselectivities are discussed.
Synthetic molecular machines hold tremendous potential to revolutionize chemical and materials sciences. Their autonomous motion controlled by external stimuli allows to develop smart materials whose ...properties can be adapted on command. For the realisation of more complex molecular machines, it is crucial to design building blocks whose properties can be controlled by multiple orthogonal stimuli. A major challenge is to reversibly switch from forward to backward and again forward light-driven rotary motion using external stimuli. Here we report a push-pull substituted photo-responsive overcrowded alkene whose function can be toggled between that of a unidirectional 2
generation rotary motor and a molecular switch depending on its protonation and the polarity of its environment. With its simplicity in design, easy preparation, outstanding stability and orthogonal control of distinct forward and backward motions, we believe that the present concept paves the way for creating more advanced molecular machines.
Light‐controlled conductance switching of diarylethenes attached to Au(111) is reported (see figure). First, scanning tunneling microscopy is used to demonstrate reversible photoswitching for ...individual molecules. Second, reversible switching in self‐assembled monolayers is established by means of optical spectroscopy.
Introduction
Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be ...diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three
18
F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria.
Methods
18
FFB-NHS and
18
FBODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed
18
FPQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites.
Results
18
FFB-vancomycin,
18
FBODIPY-FL-vancomycin, and
18
FPQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively.
18
FFB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast,
18
FBODIPY-FL-vancomycin and
18
FPQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
(MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of
18
FPQ-VE1-vancomycin and
18
FBODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones.
Conclusion
Here we present the synthesis and first evaluation of the vancomycin-based PET tracers
18
FBODIPY-FL-vancomycin and
18
FPQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.
We investigate photochromic molecular switches that are self-assembled on gold. We use two experimental techniques; namely, the mechanically controllable break-junction technique to measure ...electronic transport, and UV/Vis spectroscopy to measure absorption. We observe switching of the molecules from the conducting to the insulating state when illuminated with visible light (lambda=546 nm), in spite of the gold surface plasmon absorption present around this wavelength. However, we fail to observe the reverse process which should occur upon illumination with UV light (lambda=313 nm). We attribute this to quenching of the excited state of the molecule in the open form by the presence of gold.
Two novel bisthiourea molecular motor-based catalysts were designed and their dynamic control of activity and stereoselectivity in the Henry reaction using heat and light as external stimuli was ...investigated. Enantioselective organocatalysis studies established that a basic functional group is not required within the catalyst core to effect efficient dual stereocontrol, illustrating novel stimuli responsive organocatalysts.
In nature, key molecular processes such as communication, replication, and enzyme catalysis all rely on a delicate balance between molecular and supramolecular chirality. Here we report the design, ...synthesis, and operation of a reversible, photoresponsive, self-assembling molecular system in which molecular and supramolecular chirality communicate. It shows exceptional stereoselectivity upon aggregation of the molecules during gel formation with the solvent. This chirality is locked by photochemical switching, a process that is subsequently used to induce an inverted chiral supramolecular assembly as revealed by circular dichroism spectroscopy. The optical switching between different chiral aggregated states and the interplay of molecular and supramolecular chirality offer attractive new prospects for the development of molecular memory systems and smart functional materials.
Medical magnetic resonance imaging (MRI) produces high-resolution anatomical images of the human body, but has limited capacity to provide useful molecular information. The light-responsive, ...liposomal MRI contrast agent described herein could be used to provide an intrinsic theranostic aspect to MRI and enable tracking the distribution and cargo release of drug delivery systems upon light-triggered activation.
A liposomal MRI-probe changing relaxivity and releasing cargo upon light irradiation was developed for diagnostics and monitoring of drug delivery.
One of the key challenges in taking light‐driven unidirectional rotary motors from discovery to application is to increase the rate of rotation. Herein, we review our ongoing efforts to address this ...issue by meticulous improvement to the molecular design. To accelerate the rotary cycle, we have focused primarily on the rate‐limiting thermal isomerization step. This has been a fascinating and formidable objective, given that the first system we reported had a half‐life of over one week at room temperature! Our research has ultimately led to the construction of a unidirectional rotary molecular motor with a cycle 108 times faster than the original; that is, it can in principle function at 44 rotations per second.
Control over the rotary speed of, and, in particular, the means to accelerate, light‐driven unidirectional rotary motor systems is the key to their future application. Here, the structural features that influence the rate of rotation of molecular motors that are based on overcrowded alkenes are reviewed. This intriguing and instructive line of research ultimately leads to a motor that is capable of 44 rotations per second—5 × 108 times faster than the original design (see figure).
PDF
