Neil R. Branda

1,2-Dithienylethene Photochromes and Non-destructive Erasable Memory

Monitoring changes in ultraviolet-visible (UV-vis) absorption is not a viable method to process information for photochromic memory media due to the readout signal interfering with the photochromism. Only by monitoring the changes in other photophysical properties accompanying the photoisomerization reaction (refractive index, optical rotation, or luminescence, for example) can non-destructive, all photon-mode photochromic memory be realized. We have investigated several such systems based on 1,2-dithienylcyclopentene derivatives, which have a backbone that we consider to be currently the most promising of the photochromes. The two readout signals highlighted in this article are luminescence and optical rotation. The luminescent systems rely on porphyrinic chromophores tethered to the photochrome directly or through dative bonds. When the macrocycles are irradiated with light at wavelengths outside the absorption range of the photochrome, luminescence is only observed when the 1,2-dithienylcyclopentene backbone exists in its open-state. The self-assembly of a chiral photochromic metallo-helicate allows for stereoselective ring-closing of the 1,2-dithienylcyclopentene backbone providing a change in optical rotation that can be used as a readout signal. In the article, we also describe the use of ring-opening metathesis polymerization (ROMP) to fabricate well-ordered photochromic homopolymers possessing identical photochromic properties as their monomers.

Remote‐Control Photorelease of Caged Compounds Using Near‐Infrared Light and Upconverting Nanoparticles

The light-triggered release of molecules from “caged” forms offers the potential to deliver innocuous agents to cells, tissues, and organisms, where they can be unmasked to their active states. Because light can be readily tuned and focused, it can be spatially and temporally controlled to provide “on-command” drug delivery, unmasking of biochemical agents for enzyme and protein activation, and other biochemical and physiological studies. Several classes of small-molecule systems have been developed for use in these applications but all suffer from a serious drawback: they require high-energy ultraviolet or visible light as the trigger. Until methods that use less detrimental, lower-energy light that penetrates deeper into tissue without causing unwanted side reactions are developed, this technology will not find the widespread acceptance that it deserves. Multiphoton excitation with near-infrared (NIR) light has been presented as a practical solution to the issues associated with UV or visible light, given that it is less damaging and penetrates deeper into tissue. What prevents the general use of the multiphoton excitation technique is that many “cages” do not have large enough multiphoton cross sections in order to be susceptible to NIR light, or that their susceptibility is linked to wavelengths of light that lie outside of the tuning range of pulsed lasers. One illustrative example is the 3’,5’-dialkoxybenzoin cage 1 (Scheme 1), which together with 2-nitrobenzyl, coumarin-4-yl-methyl, p-hydroxyphenacyl, and 7-nitroindoline derivatives, is one of the most commonly employed classes of “photocages”. This versatile compound exhibits many appealing features. Its photochemistry is relatively universal, and esters, carbonates, carbamates, and phosphates can all be employed for photorelease. The high quantum yield (> 0.6) and fast rate (10–10 s ) of photolysis allows efficient release (> 95%) using short laser pulses. The photorelease does not generally lead to side reactions, and 5,7-dialkoxy-2-phenylbenzo[b]furan (2) is the only generated species (other than the released acid, alcohol, amine, or phosphate) in organic solvents. The need for unsuitable UV light in the photolysis can be overcome by coupling the 3’,5’-dialkoxybenzoin to NIRabsorbing species that act as antennae, harvest the light, and convert it into the necessary UV light through a multiphoton process. Monodispersed core–shell upconverting nanoparticles (UCNPs) composed of NaYF4 nanocrystals doped with lanthanides such as Tm and Yb (NaYF4:TmYb) are excellent candidates for this task. These UCNPs convert continuous-wave 980 nm laser light into a range of different wavelengths of light throughout the UV, visible, and NIR regions, many of which can be harnessed to drive the photoreactions of compounds anchored to their surfaces. This “remote-control” photorelease is illustrated in Scheme 2 and is the focus of the studies described herein. Although we demonstrate the success of this strategy using a model compound that releases a carboxylic acid, this approach is expected to be very general and be able to perform equally well in the release of other caged benzoin compounds. The appeal of UCNPs over multiphoton absorbing molecules can be justified on many levels. Most importantly, the Tm and Yb energy levels involved in the photophysics of the NaYF4:TmYb nanoparticles are real and the multiple absorptions are sequential, in contrast to the simultaneous absorptions needed for typical two-photon excitation. The sequential absorptions mean that the power density of the excitation source is reduced to about 10–10 orders of magnitude lower than that required for multiphoton photolysis, and allows for the employment of more economical, continuous-wave diode laser instead of a pulsed laser. In biological applications, the use of a nanoparticle as a delivery vehicle offers additional benefits compared to molecular photorelease, namely: 1) UCNPs can be coated with biocompatible polymers that render them water-soluble in order to Scheme 1. Photolysis and release of caged compounds from the generalized 3’,5’-dialkoxybenzoin structure 1 using UV light to produce 2-phenylbenzo[b]furan 2 and a carboxylic acid. Alcohols, amines, and phosphates can also be released using this approach. R=alkyl.

A Photocontrolled Molecular Switch Regulates Paralysis in a Living Organism

Using light to modulate biochemical agents in living organisms has a significant impact on photodynamic therapy and drug release. We demonstrate that a photoresponsive system can reversibly induce paralysis in nematodes as a model for living organisms when two different wavelengths of light are used to toggle the molecular switch between its two structural forms. This example illustrates how photoswitches offer great potential for advancing biomedical technologies.

Photothermal Release of Single-Stranded DNA from the Surface of Gold Nanoparticles Through Controlled Denaturating and Au−S Bond Breaking

Photothermal release of DNA from gold nanoparticles either by thermolysis of the Au-S bonds used to anchor the oligonucleotides to the nanoparticle or by thermal denaturation has great therapeutic potential, however, both processes have limitations (a decreased particle stability for the former process and a prohibitively slow rate of release for the latter). Here we show that these two mechanisms are not mutually exclusive and can be controlled by adjusting laser power and ionic strength. We show this using two different double-stranded (ds)DNA-nanoparticle conjugates, in which either the anchored sense strand or the complementary antisense strand was labeled with a fluorescent marker. The amounts of release due to the two mechanisms were evaluated using fluorescence spectroscopy and capillary electrophoresis, which showed that irradiation of the decorated particles in 200 mM NaOAc containing 10 mM Mg(OAc)(2) with a pulsed 532 nm laser operating at 100 mW favors denaturation over Au-S cleavage to an extent of more than six-to-one. Due to the use of a pulsed laser, the process occurs on the order of minutes rather than hours, which is typical for continuous wave lasers. These findings encourage continued research toward developing photothermal gene therapeutics.

An Efficient Method Based on the Photothermal Effect for the Release of Molecules from Metal Nanoparticle Surfaces

Please release me: The heat generated when metal nanoparticles absorb light results in a significant increase in the temperature of the environment around the particles and is used to selectively break bonds within a molecular system anchored to the nanoparticle surface (see picture). This process represents an advantageous and more universal method to deliver chemicals locally, while avoiding excessive tissue damage.

The Construction of (Salophen)ruthenium(II) Assemblies Using Axial Coordination

Mononuclear and binuclear carbonylruthenium(II) complexes with N2O2 Schiff base ligands based on 3,5-di-tert-butylsalicylaldehyde and three different ortho-diamines have been prepared. The mononuclear Ru(BSP)(CO) [BSP = N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-phenylenediamine] complex 4 acts as a versatile supramolecular synthon, as illustrated by the fact that it spontaneously forms linear and three-dimensional assemblies through axial coordination with pyridyl Lewis bases. Using this motif, neutral and charged assemblies 6, 9, and 12 were prepared. The versatility of the salophen ligand was highlighted by the preparation of bimetallic carbonylruthenium(II) compounds 14−17 from 1,2,4,5-tetraaminobenzene and 2,3,7,8-tetraaminodibenzo[1,4]dioxin. The bimetallic complexes were isolated as a mixture of cis and trans diastereomers with respect to the spatial relationship between the two axially bound carbon monoxide ligands. The electronic spectral and electrochemical properties of the pyridyl adducts 5, 15, and 17 were compared. The properties of 17 closely resembled 5 due to the insulating effect of the extended central tetraamino fragment, while 15 behaved as a single, novel chromophore. The electrochemical studies revealed that the central tetraamino linker regulates the communication between the two metal centers of 15 and 17. It was found that the two metal atoms of 15 sense each other to a larger extent than those of 17.

Successful Bifunctional Photoswitching and Electronic Communication of Two Platinum(II) Acetylide Bridged Dithienylethenes

Coordinating two dithienylethenes to a platinum center results in the reversible ring closure of both photochromic units in a model for a photoresponsive pi-conjugated polymer. This system demonstrates how metal-sensitized photochemistry, from a triplet excited state, circumvents the problems associated with other multicomponent photochromic systems, where significant electronic interactions in the ground state and singlet excited state prevent full photoswitching. Changes in charge-transfer behavior based upon conversion of both dithienylethenes to their ring-closed forms illustrate how photomodulation of conductivity through a conjugated polymer might be achieved using Pt-bis(acetylide)s.

Regulation of Human Carbonic Anhydrase I (hCAI) Activity by Using a Photochromic Inhibitor

Photoswitchable: The activity of a dithienylethene-based human carbonic anhydrase inhibitor (hCAI) can be regulated using light. Converting the flexible, ring-open isomer of the photoswitch into the rigid, ring-closed isomer using UV light reduces the inhibition and increases the activity of hCAI by 50-fold. The inhibitor can be turned back on by using visible light, which has many advantages in biological applications.

Limited photochromism in covalently linked double 1,2‐dithienylethenes

Only one photo-induced cyclization reaction occurs when two 1,2-dithienylethene photochromes are covalently joined. Attempts made to ring-close the second photochrome by prolonged irradiation quantitatively produced a rearranged product that could not be photobleached. Copyright

Modulating the Lewis Acidity of Boron Using a Photoswitch

Tricoordinate organoboron compounds are versatile Lewis acids used as catalysts or reagents for important organic transformations, and commercially as co-catalysts in metallocene-mediated olefin polymerization and as catalytic curing agents for epoxy resins. The Lewis acidity of boron also imparts unique properties to new p-electronic materials for use in sensing, electron-transport and other materials science applications. Integrating an external stimulus to regulate the Lewis acidity in boron-containing compounds offers a means to control chemical processes that are catalyzed by these versatile chemical species and modulate the behavior of functional materials containing them. This integration is the focus of the studies described herein. Light is a particularly effective stimulus to spatially and temporally trigger changes in structure and function of molecules and materials. This can be achieved reversibly by inducing the reactions of photochromic compounds between their two isomers, each of which have unique steric and electronic properties. Photoresponsive dithienylcyclopentenes (DTCPs) are especially appealing systems because they tend to undergo thermally irreversible ring-closing and ringopening reactions when irradiated with UV and visible light, respectively, often with a high degree of fatigue resistance (Scheme 1). There are a few examples describing how the electronic and geometric changes that accompany the photoreactions of DTCP can be used to regulate chemical reactivity and catalysis. However, these compounds exhibit only small observable effects on the rate of catalysis, and in some cases, the presence of the reactive substrate significantly reduces the photoactivity of DTCP. We have demonstrated that more dramatic changes in how each of the photoisomers behave in chemical reactions can be achieved by taking advantage of the photoinduced rearrangement of the “pi” bond in the central 5-membered ring of the DTCP. In a well-designed system, the electronic changes localized within the central cyclopentene ring are more significant than the often too subtle electronic and steric differences between the thiophene heterocycles in the ring-open and ring-closed DTCP isomers. This report describes one such example. The central 5-membered ring in compound 1a is a 1,3,2dioxaborole system in which the Lewis acidity of the boron atom can be significantly and reversibly modulated using two different wavelengths of light. The 1,3,2-dioxaborole in this ring-open isomer is a planar, conjugated system of overlapping p orbitals containing 4n+2 p electrons. It is therefore expected to have significant aromatic character and a low Lewis acidity due to the p orbital of the boron atom being partially occupied by the delocalized p electrons. Irradiation with UV light triggers the cyclization of isomer 1a to generate 1b. Now the borate group is cross-conjugated with the linearly conjugated p backbone of the rest of the molecule. This rearrangement of p electrons should reduce the amount of electron density at the boron center and turn the Lewis acid “on”. The system can be turned “off” again using visible light to reverse the cyclization reaction and regenerate the aromatic ring system. Computational investigations performed on simplified versions of isomers 1a and 1b (the three phenyl rings have been removed in 1a’ and 1b’) estimate that the ring-open form is considerably lower in energy than its ring-closed counterpart, with an energetic preference of 19.0 kcalmol , calculated at the M06-2X/DZ(2d,p) level of theory. As anticipated, the molecular orbitals of 1a’ are part of a conjugated p-orbital system that includes delocalization within the dioxaborole ring. A comparison of the lowest unoccupied molecular orbitals shows there is orbital density on the boron atom only in isomer 1b’ (Figure 1), an initial indication that there should be a difference in the Lewis acid nature between the two isomers. Other calculated values support the prediction, including the ionization potentials for 1a’ and 1b’ (calculated to be 6.90 and 6.03 eV, respectively), the difference in charge distribution on the boron established with a variety of different analyses, and calculations on the reduced forms of the two isomers, which show the energetic preference for the ring-open isomer over the ring-closed isomer drops to only a few kcalmol . Computational structures and properties of the ring-open and ring-closed isomers, 1a and 1b, are very similar to those Scheme 1. Reversible photocyclization reaction of a DTCP.