Matibur Zamadar

Toward designed singlet fission: Solution photophysics of two indirectly coupled covalent dimers of 1,3-diphenylisobenzofuran

In order to identify optimal conditions for singlet fission, we are examining the photophysics of 1,3-diphenylisobenzofuran (1) dimers covalently coupled in various ways. In the two dimers studied presently, the coupling is weak. The subunits are linked via the para position of one of the phenyl substituents, in one case (2) through a CH2 linker and in the other (3) directly, but with methyl substituents in ortho positions forcing a nearly perpendicular twist between the two joint phenyl rings. The measurements are accompanied with density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. Although in neat solid state, 1 undergoes singlet fission with a rate constant higher than 10(11) s(-1); in nonpolar solutions of 2 and 3, the triplet formation rate constant is less than 10(6) s(-1) and fluorescence is the only significant event following electronic excitation. In polar solvents, fluorescence is weaker because the initial excited singlet state S1 equilibrates by sub-nanosecond charge transfer with a nonemissive dipolar species in which a radical cation of 1 is attached to a radical anion of 1. Most of this charge transfer species decays to S0, and some is converted into triplet T1 with a rate constant near 10(8) s(-1). Experimental uncertainties prevent an accurate determination of the number of T1 excitations that result when a single S1 excitation changes into triplet excitation. It would be one if the charge-transfer species undergoes ordinary intersystem crossing and two if it undergoes the second step of two-step singlet fission. The triplet yield maximizes below room temperature to a value of roughly 9% for 3 and 4% for 2. Above ∼360 K, some of the S1 molecules of 3 are converted into an isomeric charge-transfer species with a shorter lifetime, possibly with a twisted intramolecular charge transfer (TICT) structure. This is not observed in 2.

Photosensitizer Drug Delivery via an Optical Fiber

An optical fiber has been developed with a maneuverable mini-probe tip that sparges O(2) gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d(8) (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control.

A Hand-held Fiber-optic Implement for the Site-specific Delivery of Photosensitizer and Singlet Oxygen

We have constructed a fiber optic device that internally flows triplet oxygen and externally produces singlet oxygen, causing a reaction at the (Z)‐1,2‐dialkoxyethene spacer group, freeing a pheophorbide sensitizer upon the fragmentation of a reactive dioxetane intermediate. The device can be operated and sensitizer photorelease observed using absorption and fluorescence spectroscopy. We demonstrate the preference of sensitizer photorelease when the probe tip is in contact with octanol or lipophilic media. A first‐order photocleavage rate constant of 1.13 h−1 was measured in octanol where dye desorption was not accompanied by readsorption. When the probe tip contacts aqueous solution, the photorelease was inefficient because most of the dye adsorbed on the probe tip, even after the covalent ethene spacer bonds have been broken. The observed stability of the free sensitizer in lipophilic media is reasonable even though it is a pyropheophorbide‐a derivative that carries a p‐formylbenzylic alcohol substituent at the carboxylic acid group. In octanol or lipid systems, we found that the dye was not susceptible to hydrolysis to pyropheophorbide‐a, otherwise a pH effect was observed in a binary methanol‐water system (9:1) at pH below 2 or above 8.

Singlet Oxygen Chemistry in Water: A Porous Vycor GlassSupported Photosensitizer

Singlet molecular oxygen [1O2 (1Deltag)] is generated cleanly in aqueous solution upon irradiation of a heterogeneous complex, meso-tetra(N-methyl-4-pyridyl)porphine (1) adsorbed onto porous Vycor glass (PVG). The cationic photosensitizer 1 tightly binds onto PVG and gives a stable material, which does not dissociate 1 into the surrounding aqueous phase. The production of 1O2 was measured by monitoring the time-resolved 1O2 (1Deltag) phosphorescence at 1270 nm. Indirect analysis of 1O2 generation was also carried out with the photooxidation of trans-2-methyl-2-pentenoate anion, which afforded the corresponding hydroperoxide. Sensitizer-1-impregnated PVG gives rise to a new singlet oxygen generator but more importantly provides a heterogeneous system for use in water.

Electron transfer by excited benzoquinone anions: slow rates for two-electron transitions.

Electron transfer (ET) rate constants from the lowest excited state of the radical anion of benzoquinone, BQ(-•)*, were measured in THF solution. Rate constants for bimolecular electron transfer reactions typically reach the diffusion-controlled limit when the free-energy change, ΔG°, reaches -0.3 eV. The rate constants for ET from BQ(-•)* are one-to-two decades smaller at this energy and do not reach the diffusion-controlled limit until -ΔG° is 1.5-2.0 eV. The rates are so slow probably because a second electron must also undergo a transition to make use of the energy of the excited state. Similarly, ET, from solvated electrons to neutral BQ to form the lowest excited state, is slow, while fast ET is observed at a higher excited state, which can be populated in a transition involving only one electron. A simple picture based on perturbation theory can roughly account for the control of electron transfer by the need for transition of a second electron. The picture also explains how extra driving force (-ΔG°) can restore fast rates of electron transfer.

Singlet oxygen chemistry in water. 2. Photoexcited sensitizer quenching by O2 at the water-porous glass interface.

Insight into the O2 quenching mechanism of a photosensitizer (static or dynamic) would be useful for the design of heterogeneous systems to control the mode of generation of 1O2 in water. Here, we describe the use of a photosensitizer, meso-tetra(N-methyl-4-pyridyl)porphine (1), which was adsorbed onto porous Vycor glass (PVG). A maximum loading of 1.1 x 10(-6) mol 1 per g PVG was achieved. Less than 1% of the PVG surface was covered with photosensitizer 1, and the penetration of 1 reaches a depth of 0.32 mm along all faces of the glass. Time-resolved measurements showed that the lifetime of triplet 1*-ads was 57 microseconds in water. Triplet O2 quenched the transient absorption of triplet 1*-ads; for samples containing 0.9 x 10(-6)-0.9 x 10(-8) mol 1 adsorbed per g PVG, the Stern-Volmer constant, K(D), ranged from 23,700 to 32,100 M(-1). The adduct formation constant, Ks, ranged from 1310 to 510 M(-1). The amplitude of the absorption at 470 nm decreased slightly (by about 0.1) with increased O2 concentrations. Thus, the quenching behavior of triplet 1*-ads by O2 was proposed to be strongly dependent on dynamic quenching. Only approximately 10% of the quenching was attributed to the static quenching mechanism. The quenching of triplet 1*-ads was similar to that observed for photosensitizers in homogeneous solution which are often quenched dynamically by O2.

Fiber‐optic Singlet Oxygen [1O2 (1Δg)] Generator Device Serving as a Point Selective Sterilizer

Traditionally, Type II heterogeneous photo‐oxidations produce singlet oxygen via external irradiation of a sensitizer and external supply of ground‐state oxygen. A potential improvement is reported here. A hollow‐core fiber‐optic device was developed with an “internal” supply of light and flowing oxygen, and a porous photosensitizer‐end capped configuration. Singlet oxygen was delivered through the fiber tip. The singlet oxygen steady‐state concentration in the immediate vicinity of the probe tip was ca 20 fm by N‐benzoyl‐dl‐methionine trapping. The device is portable and the singlet oxygen‐generating tip is maneuverable, which opened the door to simple disinfectant studies. Complete Escherichia coli inactivation was observed in 2 h when the singlet oxygen sensitizing probe tip was immersed in 0.1 mL aqueous samples of 0.1–4.4 × 107 cells. Photobleaching of the probe tip occurred after ca 12 h of use, requiring baking and sensitizer reloading steps for reuse.

Singlet Oxygen Delivery Through the Porous Cap of a Hollow-Core Fiber Optic Device

The development of the first photosensitizer/fiber optic device is reported. An oxygen-flowing, fiber-capped configuration is used for the application of heterogeneous, spatially confined singlet oxygen delivery in aqueous media. This is a unique device, unlike other heterogeneous photosensitizers, in which local concentrations of singlet oxygen can be delivered via introduction and withdrawal of the fiber tip.

Challenges in the Structure Determination of Self-Assembled Metallacages: What Do Cage Cavities Contain, Internal Vapor Bubbles or Solvent and/or Counterions?

Proving the structures of charged metallacages obtained by metal ion coordination-driven solution self-assembly is challenging, and the common use of routine NMR spectroscopy and mass spectrometry is unreliable. Carefully determined diffusion coefficients from diffusion-ordered proton magnetic resonance (DOSY NMR) for six cages of widely differing sizes lead us to propose a structural reassignment of two molecular cages from a previously favored trimer to a pentamer or hexamer, and another from a trimer to a much higher oligomer, possibly an intriguing tetradecamer. In the former case, strong support for the reassignment to a larger cage is provided by an observation of a slow reversible transformation of the initially formed cage into a smaller but spectrally very similar one upon dilution. In the latter case, freeze-fracture transmission electron micrographs demonstrate that at least some of the solutions are colloidal, and high-resolution electron transmission and atomic force microscopy images are compatible with a tetradecamer but not a trimer. Comparison of solute partial molar volumes deduced from measurement of solution density with volumes anticipated from molecular models argues strongly against the presence of large voids (solvent vapor bubbles) in cages dissolved in nitromethane. The presence of bubbles was previously proposed in an attempt to account for the bilinear nature of the Eyring plot of the rate constant for pyridine ligand edge exchange reaction in one of the cages and for the unusual activation parameters in the high-temperature regime. An alternative interpretation is proposed now.

Studies of Quadruplex Folding using a New Fluorescent Porphyrin Derivative

Small molecules that bind selectively to guanine-rich telomeric DNA sequences (quadruplex interactive agents; QIAs) can promote folding to a four-stranded quadruplex conformation. Such quadruplexes have been shown to deactivate telomerase, a key activating enzyme in many cancers, making QIAs promising targets for development of potential cancer drugs. Porphyrin-based QIAs offer several desirable properties as they are non-toxic and found in many oxidation-reduction proteins of the cell. In this study we have examined the effects of a new fluorescent pyropheophorbide porphyrin derivative (PPP-D) on the folding of model human telomeric DNA sequences (HT4). PPP-D demonstrates enhanced lipid solubility (log P = 6.80 ± 1.62) over other quadruplexed-DNA binding porphyrins, including meso-tetrakis(4-(N-methylpyridiumyl))porphyrin (TMPyP4) and N-methyl mesoporphyrin IX (NMM), and can facilitate cellular delivery (log P = 6.80 ± 1.62) through the cell membrane. Unlike TMPyP4 and NMM, PPP-D is non fluorescent in buffer solutions and highly fluorescent in organic solvents and non-polar environments. CD studies suggest that PPP-D successfully aids in the folding of HT4 sequences in addition to stabilizing the quadruplexed DNA conformation. Furthermore, PPP-D demonstrates selectivity for the quadruplexed (q-DNA) over duplexed DNA (d-DNA) conformation. The significance of these results for anti-tumorigenesis will be discussed. Supported by NIH-SCORE grants ISCI-GM093830-01 (AG) and S06-GM076168-01 (LD).