DNA-like Photophysics in Self-Assembled Silver(I)-Nucleobase Nanofibers.

Supramolecular assemblies form when silver nitrate is added to an aqueous solution of adenine (Ade) or 2-aminopurine (2AP) in a 2:1 mole ratio. Atomic force microscopy images reveal nanofibers that are ∼30 nm in diameter and micrometers in length in the dried film formed from a room-temperature solution. Femtosecond broadband transient absorption spectroscopy was used to investigate the dynamics of excited states formed by UV excitation of the nanofibers in room-temperature aqueous solutions in an effort to learn how nonradiative decay pathways of the uncomplexed nucleobases are altered in the silver-ion-mediated assemblies. The changes in the spectroscopy and dynamics of Ade and 2AP upon forming nanofibers with silver ions closely parallel the ones seen when these bases are organized into DNA strands. The similarities strongly suggest that these structures feature extensive π-π stacking interactions between nucleobases. The results show that time-resolved spectroscopy combined with growing understanding of the photophysics of DNA strands can deliver new insights into the properties of metal-nucleobase nanoassemblies.

Ultrafast Pump-Repump-Probe Photochemical Hole Burning as a Probe of Excited-State Reaction Pathway Branching.

We demonstrate pump-repump-probe (PRP) transient hole burning as a spectroscopic tool for differentiating reactive from nonreactive deactivation of excited photochemical reactants observed by transient absorption spectroscopy (TAS). This method utilizes a time-delayed, wavelength-tunable ultrafast pulse to alter the excited reactant population, with the impact of "repumping" quantified through depletions in photoproduct absorption. We apply this approach to characterize dynamics affecting the nonadiabatic photocyclization efficiency to form S0 dihydrotriphenylene (DHT) following 266 nm excitation of ortho-terphenyl (OTP). TAS studies revealed bimodal deactivation of OTP*, but neither relaxation time scale (700 fs and 3.0 ps) could be assigned unambiguously to DHT formation due to overlap of excited-state and product spectra. PRP studies reveal that S1 OTP only cyclizes on the slower of these time scales, with the faster process attributable to nonreactive deactivation. We demonstrate that this method offers greater photochemical insights without assuming models to globally fit spectral transients collected by TAS.

BN Doping and the Photochemistry of Polyaromatic Hydrocarbons: Photocyclization of Hexaphenyl Benzene and Hexaphenyl Borazine.

Boron-nitrogen doping of polyaromatic hydrocarbon (PAH) materials can be used to tune their electronic properties while preserving the structural characteristics of pure hydrocarbons. Many multicycle PAHs can be synthesized photochemically; in contrast, very little is known about the photochemistry of their BN-doped counterparts. We present results of fs, ns, and µs time-resolved spectroscopic studies on the photoinduced dynamics of hexaphenyl benzene and hexaphenyl borazine in order to examine how BN doping alters photochemical C-C bond formation via 6π electrocyclization as well as the stability of resulting cyclized structures. Ultrafast measurements reveal photoinduced behaviors reflecting differences in excited-state decay pathways for the two molecules, with hexaphenyl borazine relaxing from its excited state with a rate that is 2 orders of magnitude faster than that of hexaphenyl benzene (3.0 vs 428 ps). Tetraphenyl dihydrotriphenylene generated from hexaphenyl benzene is observed to reopen with a ∼2 µs lifetime controlled by entropic stabilization of the cyclized structure; in contrast, photoinduced dynamics appear to be complete within 100 ps after excitation of hexaphenyl borazine. This significant difference in photochemical dynamics is reflected in the cyclodehydrogentation yields obtained for the two reactants (25 vs 0% for hexaphenyl benzene and borazine, respectively). Quantum-chemical computations predict that BN doping gives rise to energetic destabilization and increased singlet diradical character in cyclized structures. These findings indicate that the polarized BN bonds of the borazine core adversely impact photochemical bond formation relative to analogous hydrocarbons.

Excited-State Deactivation Pathways and the Photocyclization of BN-Doped Polyaromatics.

Boron-nitrogen doping of polyaromatic hydrocarbons (PAH), such as borazine-core hexabenzocoronene, presents possibilities for tuning the properties of organic electronics and nanographene materials while preserving structural characteristics of pure hydrocarbons. Previous photochemical studies have demonstrated extension of a borazine-core PAH network (1,2:3,4:5,6-tris(o,o'-biphenylylene)borazine, 1) by photoinduced cyclodehydrogenation. We present steady-state and femtosecond-to-microsecond resolved spectroscopic studies of the photophysics of 1 and a related borazine-core PAH in order to characterize competing excited-state relaxation pathways that determine the efficacy of bond formation by photocyclization. Transient spectra evolve on time scales consistent with S1 fluorescence lifetimes (1-3 ns) to features that persist onto microsecond time scales. Nanosecond-resolved oxygen-quenching measurements reveal that long-lived metastable states are triplets rather than cyclized products. Determination of fluorescence and triplet quantum yields reveal that photochemical bond formation is a minor channel in the relaxation of 1 (∼5% or less), whereas highly efficient fluorescence and intersystem crossing result in negligible photoinduced bond formation in more extended borazine-core networks. Results of computational investigations at the RICC2 level reveal sizable barriers to cyclization on the S1 potential energy surfaces consistent with quantum yields deduced from experiment. Together these barriers and competing photophysical pathways limit the efficiency of photochemical synthesis of BN-doped polyaromatics.

Aminofluorination of Cyclopropanes: A Multifold Approach through a Common, Catalytically Generated Intermediate.

We have discovered a highly regioselective aminofluorination of cyclopropanes. Remarkably, four unique sets of conditions-two photochemical, two purely chemical-generated the same aminofluorinated adducts in good to excellent yields. The multiple, diverse ways in which the reaction could be initiated provided valuable clues that led to the proposal of a "unifying" chain propagation mechanism beyond initiation, tied by a common intermediate. In all, the proposed mechanism herein is substantiated by product distribution studies, kinetic analyses, LFERs, Rehm-Weller estimations of ΔGET, competition experiments, KIEs, fluorescence data, and DFT calculations. From a more physical standpoint, transient-absorption experiments have allowed direct spectroscopic observation of radical ion intermediates (previously only postulated or probed indirectly in photochemical fluorination systems) and, consequently, have provided kinetic support for chain propagation. Lastly, calculations suggest that solvent may play an important role in the cyclopropane ring-opening step.

Structural Control of Nonadiabatic Photochemical Bond Formation: Photocyclization in Structurally Modified ortho-Terphenyls.

Understanding how molecular structure impacts the shapes of potential energy surfaces and prospects for nonadiabatic photochemical dynamics is critical for predicting and controlling the chemistry of molecular excited states. Ultrafast transient absorption spectroscopy was used to interrogate photoinduced, nonadiabatic 6π cyclization of a collection of ortho-terphenyls (OTP) modified with alkyl substituents of different sizes and electron-donating/withdrawing character positioned on its central and pendant phenyl rings. OTP alkylated at the 4,4″ and 4',5' positions of the pendant and central rings, respectively, exhibiting biphasic excited-state relaxation; this is qualitatively similar to relaxation of OTP itself, including a fast decrease in excited-state absorption (τ1 = 1-4 ps) followed by formation of metastable cyclized photoproducts (τ2 = 3-47 ps) that share common characteristic spectroscopic features for all substitutions despite variations in chemical nature of the substituents. By contrast, anomalous excited-state dynamics are observed for 3',6'dimethyl-OTP, in which the methyl substituents crowd the pendant rings sterically; time-resolved spectral dynamics and low photochemical reactivity with iodine reveal that methylation proximal to the pendant rings impedes nonadiabatic cyclization. Results from transient measurements and quantum-chemical calculations are used to decipher the nature of excited state relaxation mechanisms in these systems and how they are perturbed by mechanical, electronic, and steric interactions induced by substituents.

Structural control of nonadiabatic bond formation: the photochemical formation and stability of substituted 4a,4b-dihydrotriphenylenes.

Nonadiabatic photocyclization makes bonds and is the first step in the photoinduced cyclodehydrogenation of ortho-arenes to yield polycyclic aromatic hydrocarbons. How molecular structure alters potential-energy landscapes, excited-state dynamics, and stabilities of reactants and intermediates underlies the feasibility of desirable photochemistry. In order to gain insight into these structure-dynamics relationships, we have used femtosecond transient absorption spectroscopy (TAS) to examine photoinduced dynamics of 1,2,3-triphenylbenzene (TPB) and ortho-quaterphenyl (OQTP), phenyl-subsituted analogues of ortho-terphenyl (OTP). Dynamics of TPB and OTP are quite similar: TPB exhibits fast (7.4 ps) excited-state decay with concomitant formation and vibrational relaxation of 9-phenyl-dihydrotriphenylene (9-phenyl DHT). In contrast, photoexcited OQTP exhibits multistate kinetics leading to formation of 1-phenyl DHT. Excited-state calculations reveal the existence of two distinct minima on the OQTP S1 surface and, together with photophysical data, support a mechanism involving both direct cyclization by way of an asymmetric structure and indirect cyclization by way of a symmetric quinoid-like minimum. Temperature-dependent nanosecond TAS was utilized to assess the relative stabilities of intermediates, substantiating the observed trend in photochemical reactivity OTP > OQTP > TPB. In total, this work demonstrates how specific structural variations alter the course of the excited-state dynamics and photoproduct stability that underlies desired photochemistry.

Structural and solvent control of nonadiabatic photochemical bond formation: photocyclization of o-terphenyl in solution.

Elucidating the molecular dynamics that underlie photoinduced electrocyclization is a critical step toward controlling nonadiabatic photochemistry that enables bond formation. Here we present a comprehensive examination of the photochemical dynamics of o-terphenyl (OTP) in solution. Ultrafast transient absorption measurements demonstrate that OTP cyclizes upon 266 nm photoexcitation to form 4a,4b-dihydrotriphenylene (DHT) on a solvent-dependent time scale of 1.5-4 ps, considerably slower than the nonadiabatic cyclization of related diarylethenes. Correlations in these time scales versus bulk solvent properties reveal that mechanical rather than electrostatic solvent-solute interactions impact the excited-state relaxation rate, impeding nuclear dynamics leading toward the conical intersection for cyclization. In contrast, solvent-dependent mechanical interactions are observed to facilitate vibrational relaxation of DHT on time scales of 10-25 ps. DHT decays via thermally activated ring-opening with a lifetime of ∼46 ns in tetrahydrofuran, 12 orders of magnitude faster than dihydrophenanthrenes. We conclude that the differences in excited-state dynamics of OTP and diarylethenes and the relative stability of their cyclized products are determined by the relative strain induced by twisting the central carbon-carbon bond that bridges the terminal phenyl rings in each to enable bond formation. We relate these structure-dynamics relationships to the feasibility of photoinduced cyclodehydrogenation of o-arenes and design considerations for molecular photoswitches.

Ultrafast Excited-State Dynamics of ortho-Terphenyl and 1,2-Diphenylcyclohexene: The Role of "Ethylenic Twisting" in the Nonadiabatic Photocyclization of Stilbene Analogs.

Nonadiabatic photocyclization is the fundamental step underlying photoswitching and light-assisted bond formation within diarylethylenes, yet the details of the nuclear dynamics leading to cyclization remain unclear. We have examined the ultrafast excited-state dynamics of o-terphenyl (OTP) and 1,2-diphenylcyclohexene (DPCH) in solution to determine how variation in structural constraints impacts the course of nonadiabatic photocyclization specifically in stilbenoids. Measured spectral dynamics reflect cyclization through a S1-to-S0 transition for both systems on picosecond time scales, with excited-state decay appreciably faster for DPCH versus OTP. Supportive ab initio calculations reveal a higher energetic penalty in OTP versus DPCH for reaching the lowest-energy conical intersection from the S1 minimum; this penalty is associated primarily with twisting about the carbon-carbon bond that bridges terminal phenyl groups, a structural change that has a critical role in nonadiabatic cis-trans isomerization of diarylethylenes. Findings provide a new experimental perspective on the elusive nuclear dynamics underlying cis-stilbene photocyclization.

Prenatal lipopolysaccharide does not accelerate progressive dopamine neuron loss in the rat as a result of normal aging.

We previously demonstrated that in utero exposure to the bacteriotoxin lipopolysaccharide (LPS) led to the birth of rat pups with fewer than normal dopamine (DA) neurons. These animals exhibited significant neuroinflammation in the nigrostriatal pathway creating the possibility that they could exhibit further, progressive DA neuron loss over their lives. To study this possibility, we injected gravid female rats i.p. at 10,000 endotoxin units (EUs) of LPS per kg or saline at embryonic (E) day 10.5 and assigned pups to sacrifice groups at 4, 14 and 17 months such that littermates were sacrificed at each end point. The effects of prenatal LPS on DA cell counts and striatal DA were significantly reduced relative to controls whereas DA activity and numbers of activated microglia (OX-6ir cell) were statistically increased. However, the progressive DA neuron loss was parallel to that of the controls suggesting that prenatal LPS does not produce an accelerated rate of DA neuron loss. Interestingly, locomotor activity was increased after 3 months in animals exposed to LPS prenatally, but by 16 months, was significantly reduced relative to controls. Additionally, animals exposed to LPS prenatally exhibited Lewy body-like inclusions that were first seen in 14 month old animals. These data broadly support previous studies demonstrating that prenatal exposure to LPS, as frequently occurs in humans as part of Bacterial Vaginosis, leads to the birth of animals with fewer than normal DA neurons. The progressive DA neuron loss seen in these animals is, however, primarily a result of normal aging.

Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally.

Toxin-induced animal models of Parkinson's disease (PD) exhibit many of the same neuroinflammatory changes seen in patients suggesting a role for inflammation in DA neuron loss. Yet, despite this inflammation, the progressive loss of DA neurons that characterizes PD is rarely seen in animals. We infused lipopolysaccharide (LPS) or saline into 7-month-old rats that had been exposed to LPS or saline prenatally and assessed them for DA neuron loss and inflammatory measures (interleukin 1 beta, tumor necrosis factor-alpha, glutathione, and activated microglia) over a period of 84 days to examine the role of pre-existing inflammation in progressive DA neuron loss. LPS infusion into both prenatal treatment groups produced neuroinflammation during the 14 days of LPS infusion that subsequently reverted toward normal over the next 70 days. In animals with pre-existing inflammation (i.e., prenatal LPS), however, the acute changes seen were attenuated, but took much longer to return to normal suggesting a prolonged inflammatory response. These inflammatory changes were consistent with the greater acute DA neuron loss seen in the prenatal saline controls and the progressive DA neuron loss seen only in the animals exposed to LPS prenatally. Interestingly, both prenatal treatment groups exhibited increases in microglia over the entire 84-day course of the study. These data suggest that pre-existing neuroinflammation prolongs the inflammatory response that occurs with a second toxic exposure, which may be responsible for progressive DA neuron loss. This provides further support for the "multiple hit" hypothesis of PD.