On the Transition from a Biomimetic Molecular Switch to a Rotary Molecular Motor.

The experimental investigation of the unidirectional motion characterizing the photoisomerization of single-molecule rotary motors requires accessible lab prototypes featuring an electronic circular dichroism (ECD) signal that is sensitive to the geometrical and electronic changes occurring during an ultrafast reactive process. Here we report a combined experimental/computational study of a candidate obtained via the asymmetrization of a light-driven biomimetic molecular switch. We show that the achieved motor has an ECD band that is remarkably sensitive to the isomerization motion, and it is therefore suitable for time-resolved ECD studies.

Synthesis, spectroscopy and QM/MM simulations of a biomimetic ultrafast light-driven molecular motor.

A molecular motor potentially performing a continuous unidirectional rotation is studied by a multidisciplinary approach including organic synthesis, transient spectroscopy and excited state trajectory calculations. A stereogenic center was introduced in the N-alkylated indanylidene-pyrroline Schiff base framework of a previously investigated light-driven molecular switch in order to achieve the unidirectional C[double bond, length as m-dash]C rotary motion typical of Feringa's motor. Here we report that the specific substitution pattern of the designed chiral molecule must critically determine the unidirectional efficiency of the light-induced rotary motion.

Bile Acid Binding Protein Functionalization Leads to a Fully Synthetic Rhodopsin Mimic.

Rhodopsins are photoreceptive proteins using light to drive a plethora of biological functions such as vision, proton and ion pumping, cation and anion channeling, and gene and enzyme regulation. Here we combine organic synthesis, NMR structural studies, and photochemical characterization to show that it is possible to prepare a fully synthetic mimic of rhodopsin photoreceptors. More specifically, we conjugate a bile acid binding protein with a synthetic mimic of the rhodopsin protonated Schiff base chromophore to achieve a covalent complex featuring an unnatural protein host, photoswitch, and photoswitch-protein linkage with a reverse orientation.

Engineering the vibrational coherence of vision into a synthetic molecular device.

The light-induced double-bond isomerization of the visual pigment rhodopsin operates a molecular-level optomechanical energy transduction, which triggers a crucial protein structure change. In fact, rhodopsin isomerization occurs according to a unique, ultrafast mechanism that preserves mode-specific vibrational coherence all the way from the reactant excited state to the primary photoproduct ground state. The engineering of such an energy-funnelling function in synthetic compounds would pave the way towards biomimetic molecular machines capable of achieving optimum light-to-mechanical energy conversion.

Design, Synthesis, and Dynamics of a Green Fluorescent Protein Fluorophore Mimic with an Ultrafast Switching Function.

While rotary molecular switches based on neutral and cationic organic π-systems have been reported, structurally homologous anionic switches providing complementary properties have not been prepared so far. Here we report the design and preparation of a molecular switch mimicking the anionic p-HBDI chromophore of the green fluorescent protein. The investigation of the mechanism and dynamics of the E/Z switching function is carried out both computationally and experimentally.

Initial excited-state dynamics of an N-alkylated indanylidene-pyrroline (NAIP) rhodopsin analog.

N-Alkylated indanylidene-pyrroline-based molecular switches mimic different aspects of the light-induced retinal chromophore isomerization in rhodopsin: the vertebrate dim-light visual pigment. In particular, they display a similar ultrashort excited-state lifetime, subpicosecond photoproduct appearance time, and photoproduct vibrational coherence. To better understand the early light-induced dynamics of such systems, we measured and modeled the resonance Raman spectra of the Z-isomer of the N-methyl-4-(5'-methoxy-2',2'-dimethyl-indan-1'-ylidene)-5-methyl-2,3-dihydro-2H-pyrrolium (NAIP) switch in methanol solution.

Mechanistic origin of the vibrational coherence accompanying the photoreaction of biomimetic molecular switches.

The coherent photoisomerization of a chromophore in condensed phase is a rare process in which light energy is funneled into specific molecular vibrations during electronic relaxation from the excited to the ground state. In this work, we employed ultrafast spectroscopy and computational methods to investigate the molecular origin of the coherent motion accompanying the photoisomerization of indanylidene-pyrroline (IP) molecular switches. UV/Vis femtosecond transient absorption gave evidence for an excited- and ground-state vibrational wave packet, which appears as a general feature of the IP compounds investigated.

Photoisomerization and relaxation dynamics of a structurally modified biomimetic photoswitch.

Recent experimental and theoretical studies on N-alkylated indanylidene pyrroline Schiff bases (NAIP) show that these compounds exhibit biomimetic photoisomerization analogous to that in the chromophore of rhodopsin. The NAIP compounds studied previously isomerize rapidly and often evolve coherently on the ground-electronic surface after reaction. We present the results of transient electronic absorption spectroscopy on dMe-OMe-NAIP, a newly synthesized NAIP analogue that differs from other NAIP compounds in the substituents on its pyrrolinium ring.

Toward a stable α-cycloalkyl amino acid with a photoswitchable cationic side chain.

The N-alkylated indanylidenepyrroline (NAIP) Schiff base 3 is an unnatural α-amino acid precursor potentially useful for the preparation of semisynthetic peptides and proteins incorporating charged side chains whose structure can be modulated via Z/E photoisomerization. Here we report that the heteroallylic protons of 3 led to partial loss of ethanol accompanied by formation of the novel heterocyclic system 4 during attempted deprotection. We also show that the same protons catalyze the thermal isomerization of 3, making the light-driven conformational control concept ineffective for times longer than a few hours.

Modeling, preparation, and characterization of a dipole moment switch driven by Z/E photoisomerization.

We report the results of a multidisciplinary research effort where the methods of computational photochemistry and retrosynthetic analysis/synthesis have contributed to the preparation of a novel N-alkylated indanylidene-pyrroline Schiff base featuring an exocyclic double bond and a permanent zwitterionic head. We show that, due to its large dipole moment and efficient photoisomerization, such a system may constitute the prototype of a novel generation of electrostatic switches achieving a reversible light-induced dipole moment change on the order of 30 D. The modeling of a peptide fragment incorporating the zwitterionic head into a conformationally rigid side chain shows that the switch can effectively modulate the fluorescence of a tryptophan probe.

Fluorenylidene-pyrroline biomimetic light-driven molecular switches.

A new family of biomimetic photoactivated molecular switches based in the retinal chromophore is described. Expedient synthesis allows a library of compounds with a different substitution pattern, including chiral substituents, to be obtained. The effect of substitution, solvent, and light source on the photoisomerization step has been assessed.

An artificial molecular switch that mimics the visual pigment and completes its photocycle in picoseconds.

Single molecules that act as light-energy transducers (e.g., converting the energy of a photon into atomic-level mechanical motion) are examples of minimal molecular devices.

Heteroaryl-substituted phenols as potential antioxidants.

A series of O-heteroaryl phenols have been synthesised and structurally characterised. Photo-Fries rearrangement of these compounds represents a useful way to access the corresponding C-heteroaryl derivatives. The activity of the new phenolic compounds as radical scavengers towards the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS(+*)) has been evaluated.

Design and photochemical characterization of a biomimetic light-driven Z/E switcher.

Protonated Schiff bases (PSBs) of polyenals constitute a class of light-driven switchers selected by biological evolution that provide model compounds for the development of artificial light-driven molecular devices or motors. In the present paper, our primary target is to show, through combined computational and experimental studies, that it is possible to approach the design of artificial PSBs suitable for such applications. Below, we use the methods of computational photochemistry to design and characterize the prototype biomimetic molecular switchers 4-cyclopenten-2'-enylidene-3,4-dihydro-2H-pyrrolinium and its 5,5'-dimethyl derivative both containing the penta-2,4-dieniminium chromophore.