Dansyl Emits from a PICT Excited State.

Two derivatives of dansyl (1-dimethylamino-5-naphthalenesulfonyl) in which the amino group is constrained in a ring are prepared as neopentyl esters. Their photophysical behavior is compared with that of the dansyl ester. The solvatochromism and quantum yields are similar for all three. Since the two constrained derivatives cannot twist about the amino group, they must emit from a planar intramolecular charge-transfer excited state. The similar photophysical behavior suggests that dansyl also emits from a PICT excited state instead of a twisted intramolecular charge transfer state.

Synthesis and Spectrophotometric Analysis of 1-Azafluorenone Derivatives.

A new extension for the 'one pot' construction of diverse 1-azafluorene derivatives featuring a Diels-Alder/retro-Diels-Alder cycloaddition is reported. Conditions were also determined for oxidation to the derived azafluorenones. The spectrophotometric analysis of five different azafluorenones were performed. Moderate fluorescence was observed with azafluorenone derivatives that bear an imbedded pyridone motif; whereas those bearing substituted pyridines do not fluoresce.

Dynamical signatures from competing, nonadiabatic fragmentation pathways of S-nitrosothiophenol.

S-Nitrosothiols (RSNOs) are derived from the combination of sulfur and nitric oxide (NO) radicals in the Earth's atmosphere and fragment to products following photolysis. Extensive theoretical studies have focused on the thermodynamic and, to a lesser extent, photochemical properties of RSNOs. However, experimental studies of these compounds have been limited due to the inherent instability of RSNOs at room temperature. Using velocity map imaging (VMI), we explore the photodissociation dynamics of jet-cooled S-nitrosothiophenol (PhSNO) from 355 nm photolysis. We report the translational and internal energy distributions of the NO and thiophenoxy (PhS) co-fragments, which are determined by spatial detection of the ionized NO photofragments using 1+1 resonance-enhanced multiphoton ionization (REMPI). The velocity distributions indicate competing PhSNO nonadiabatic dissociation pathways, in which PhS is formed in the ground and first excited electronic states when probing high- and low-energy NO (X2Π1/2, v'', J'') rovibrational states, respectively. The results of multireference electronic structure calculations suggest that direct dissociation on the bright S2 state results in PhS formed in its excited electronic state, whereas intersystem crossing into the triplet manifold leads to population of PhS in its electronic ground state. The dynamical signatures from the dissociation processes are imprinted on the fragments' quantum states and relative translation, which we explore in rigorous detail using state-resolved imaging and high-level theoretical calculations.

Fluorescence Quenching of Carbonyl-Twisted 5-Acyl-1-dimethylaminonaphthalenes by Alcohols.

Derivatives of 1-dimethylamino-5-propionylnaphthalene that constrain the carbonyl group into a five-, six-, and seven-membered ring were prepared, and their fluorescence quenching in protic solvents was studied. Evidence for enhanced quenching due to carbonyl twisting out of the molecular plane is presented, but this effect is heavily masked by the strong quenching by all of the derivatives and by the ring size-dependent deactivation seen in polar, aprotic solvents. Calculations show strong, ring size-dependent vibrational coupling between the carbonyl group and the naphthalene ring in the first excited state.

1,5-Prodan Emits from a Planar Intramolecular Charge-Transfer Excited State.

1-Propionyl-5-dimethylaminonaphthalene (8, 1,5-Prodan) and two derivatives where the amino group is constrained in a seven-membered (9) and five-membered (10) ring are prepared. All three exhibit strong fluorescence and similar degrees of solvatochromism. Their fluorescence is strongly quenched in alcohol solvents. Because the amino group in 9 and especially 10 is forced to be coplanar with the naphthalene ring, the similar photophysical behavior of all three suggests that emission arises from a planar excited state (planar intramolecular charge transfer).

Stereoelectronics of the Hydrogen-Bond-Induced Fluorescence Quenching of 3-Aminofluorenones with Alcohols.

Two derivatives of 3-amino-9-fluorenone (1) bearing one (2) and two methyl (3) groups flanking the carbonyl group are prepared. Comparison of their photophysical properties show that all suffer efficient radiationless deactivation in the presence of alcohols. Preferential solvation studies with mono alcohols reveal that a single H-bonding interaction quenches the excited states of 1 and 2, but not that of 3. In contrast, a single molecule of ethylene glycol quenches all three. These results are interpreted in a quenching mechanism similar to one proposed by Inoue and co-workers, but where an out-of-plane H-bond with the carbonyl group gives rise to an emissive species, while an in-plane H-bond results in quenching.

Intramolecular Hydrogen-Bonding Effects on the Fluorescence of PRODAN Derivatives.

The effects of intramolecular hydrogen-bonding on the fluorescence behavior of three derivatives of 6-propionyl-2-dimethylaminonaphthalene are reported. The H-bonding effects are revealed through comparisons with corresponding reference compounds in which the H-bond-donating hydroxyl groups are replaced with methoxy groups. In toluene, intramolecular H bonding gives rise to a dramatic increase in the fluorescence intensity but only a slight red shift in the position. This behavior is attributed to decreased efficiency in intersystem crossing due to an increase in the energy of the n → π* triplet state. The intramolecular H bond does not induce quenching in acetonitrile; however, in the presence of a very small concentration of methanol, a dual intramolecular, intermolecular H-bonding arrangement does lead to partial quenching as revealed by preferential solvation studies.

Dual-sensor fluorescent probes of surfactant-induced unfolding of human serum albumin.

Two extrinsic fluorescent probes, 3-(dimethylamino)-8,9,10,11-tetrahydro-7H-cyclohepta[a]naphthalen-7-one (1) and 7-(dimethylamino)-2,3-dihydrophenanthren-4(1H)-one (2), are used to probe the unfolding of human serum albumin by sodium dodecyl sulfate (SDS). These probes respond separately to the polarity and H-bond-donating ability of their surroundings. Competitive binding experiments show that fluorophore 1 binds to site I (domain IIA) and 2 binds to site II (domain IIIA). The local acidity of 1 in site I is out of the sensing range of 1, whereas the local acidity of 2 in site II is calculated to be nearly zero on Catalan's solvent acidity index. Both probes show that the first two equivalents of bound SDS result in a decrease in the local polarity of the binding sites. Each subsequent equivalent of SDS gives rise to a dramatic increase in polarity until HSA is saturated with seven molecules of SDS at the end of the specific binding domain. Compound 2 experiences an increase of acidity of 0.10 on Catalan's solvent acidity index through seven equivalents of SDS, but the local acidity for 1 is still out of range. The increase in acidity experienced by 2 is greater than the increase in polarity. This result is consistent with greater exposure of the carbonyl group in 2, but not the bulk of 2, to the aqueous solvent in site II of the SDS-saturated HSA complex.

2,5-PRODAN derivatives as highly sensitive sensors of low solvent acidity.

Two 5-acyl-2-dimethylaminonaphthalene derivatives, one with a propionyl group and the other with a fused cyclohexanone ring, are investigated as sensors of H-bond-donating ability in protic solvents of low solvent acidity. Their fluorescence is highly quenched in protic solvents, and the quenching order of magnitude is linearly related to the H-bond-donating ability of the solvent as quantified by the solvent acidity (SA) scale. As the solvent acidity increases from 0.15 to 0.40, the fluorescence for both is quenched by more than a factor of ten; thus, they are extremely sensitive sensors of the hydrogen-bond-donating ability in this weakly acidic range. Preferential solvation studies suggest that quenching occurs from a doubly H-bonded excited state.

Preferential solvation in carbonyl-twisted PRODAN derivatives.

The Rosés and Bosch model for preferential solvation is used to analyze the fluorescence behavior of two PRODAN derivatives in binary solvents with one or two protic components. The preferential solvation results suggest that the excited PRODAN derivatives form two H-bonds. The model allows for determining the characteristics of the singly H-bonded excited states. They show red-shifted fluorescence but relatively little quenching. In contrast, the doubly H-bonded excited states are significantly quenched when the protic solvent is a strong H-bond donor (large SA value). With two protic solvents there is little preferential interaction even though the solvents have very different H-bond-forming ability.

Local solvent acidities in ß-cyclodextrin complexes with PRODAN derivatives.

The local solvent acidities (SA scale) of six 6-carbonyl-2-aminonaphthalene derivatives as ß-cyclodextrin complexes in water are determined through fluorescence quenching. The local polarities (E(T)(N) scale) are determined through the shift of the emission center-of-mass. The apparent SA values reflect the solvent structure surrounding the guest's carbonyl group, whereas the apparent E(T)(N) values reveal the net polarity of the entire guest molecule. Comparison of these values affords greater insight into the structures of the host­guest complexes. Derivatives 1 and 5 show unusually large acidities, indicative of highly exposed carbonyl groups. The remaining compounds give emission intensities pointing to shielded carbonyl groups. In this study, PRODAN and its derivatives are functioning as dual channel sensors of their local environment.

Carbonyl-twisted 6-acyl-2-dialkylaminonaphthalenes as solvent acidity sensors.

Derivatives of 2-propionyl-6-dimethylaminonaphthalene (PRODAN) with twisted carbonyl groups were investigated as highly responsive sensors of H-bond donating ability. The PRODAN derivative bearing a pivaloyl group (4) was prepared. The torsion angle between the carbonyl and naphthalene is 26° in the crystal. It shows solvatochromism that is similar to five other PRODAN derivatives (1-3, 5, 6). Twisted-carbonyl derivatives 3, 4, and 6 show strong fluorescence quenching in protic solvents. The order of magnitude of the quenching is linearly related to the H-bond donating ability of the solvent (SA) but not to other solvent properties. Binary mixtures of protic solvents show specific interaction effects with respect to quenching and solvatochromism. Aggregation in water is an issue with the pivaloyl derivatives.

Synthesis and Properties of Two PRODAN-based Fluorescent Models of Cholesterol.

The syntheses and photophysical properties of 1-(5-methylhexyl)-2,3,7,8-tetrahydro-1H-naphtho[2,1-e]indol-9(6H)-one (7a) and 1-(5-methylhexyl)-2,3,8,9-tetrahydro-1H-naphtho[2,1-e]indol-6(7H)-one (7b) are reported. They are prepared in eight steps from the corresponding bromonaphthylamines. These fluorescent compounds have PRODAN-like cores, and they are structurally similar to cholesterol. Compound 7a is the first reported PRODAN derivative where both the amino and carbonyl groups are constrained to be coplanar with the naphthalene core. Comparing the photophysical behavior of these compounds with related compounds indicates that locking the amino group in a five-membered ring enhances their desirable properties as solvent polarity sensors.

2,5-PRODAN: synthesis and properties.

The preparations of 1-(6-(dimethylamino)naphthalen-1-yl)propan-1-one (2,5-PRODAN, 2) and 7-(dimethylamino)-2,3-dihydrophenanthren-4(1H)-one 3 are described. The photophysical properties of these compounds are characterized and compared with those of PRODAN. Both compounds show solvatochromism that is similar in magnitude to PRODAN with a quantum yield that is nearly one order of magnitude smaller. Emission occurs from a locally excited (LE) state with charge-transfer character. There is no internal conversion to a different charge-transfer state as is seen in PRODAN.

Does PRODAN possess an O-TICT excited state? Synthesis and properties of two constrained derivatives.

The synthesis and photophysical properties of 7-(dimethylamino)-3,4-dihydrophenanthren-1(2H)-one (7) and 3-(dimethylamino)-8,9,10,11-tetrahydro-7H-cyclohepta[a]naphthalen-7-one (8) are reported. These compounds possess a cycloalkanone substructure that controls the extent of twisting of the carbonyl group. The six-membered ring in 7 forces the carbonyl group to be coplanar with the naphthalene ring, whereas the seven-membered ring in 8 induces a significant twist. Both have the substructure of PRODAN (6-propionyl-2-(dimethylamino)naphthalene, 1). Comparing the photophysical behavior of these compounds with that of PRODAN and 2,2-dimethyl-1-(4-methyl-1,2,3,4-tetrahydrobenzo[f]quinolin-8-yl)propan-1-one (3) indicates that PRODAN likely emits from a PICT excited state rather than from an O-TICT excited state.

Phenolphthalein as a prototype drug for a group of structurally related calcium channel blockers in human platelets.

Thrombin increases intracellular free Ca ([Ca]i) in human platelets by 2 mechanisms: internal mobilization and the influx of Ca via store-operated Ca entry (SOCE). 2-Aminoethoxydiphenyl borate (2-APB) is an inhibitor of SOCE. In search for nonboron analogues of 2-APB, we identified a well-known compound, phenolphthalein, structurally related to 2-APB. Many phenolphthalein analogues inhibited the ability of thrombin and thapsigargin (a specific activator of SOCE) to increase [Ca]i. Phenolphthalein has an IC50 approximately 10 microM to inhibit thrombin-induced [Ca]i elevation, its active analogues have a similar potency. Several phenolphthalein analogues also inhibited thrombin-induced intracellular Ca mobilization, which indicates action on inositol 1,4,5-trisphosphate receptors. We identified structural features among active and inactive phenolphthalein analogues that are responsible for the activity. Opening of the 5-membered lactone ring of phenolphthalein resulted in a total loss of activity. If the diphenyl rings possessed primary amine, dimethyl amine, or a cyano group, there was no activity. Modifications to the diphenyl groups that were tolerated include phosphate, sulfate, iodine, bromine, methyl, nitrite, and methoxy. Inhibition of thrombin-induced [Ca]i increase by phenolphthalein was not mediated by an increase in cyclic adenosine monophosphate because the inhibitor of cyclic adenosine monophosphate-dependent protein kinase A, 4-cyano-3-methylisoquinoline, did not affect the inhibitory action of phenolphthalein. The inhibitory effect of phenolphthalein was not mediated by an increase in NO/cyclic guanosine monophosphate (cGMP) because the inhibitors of NO-sensitive soluble guanylyl cyclase, methylene blue, and ODQ did not affect the inhibition. Phytohemagglutinin and thapsigargin-induced SOCE in Jurkat cells was also inhibited by phenolphthalein and 2-APB to the same extent as seen in platelets. Therefore, phenolphthalein and its derivatives structurally similar to 2-APB inhibit SOCE in platelets and other cells.

Latent synthesis of electrically conductive surface-silvered polyimide films.

A facile ambient temperature route to the fabrication of surface silver-metallized polyimide films is described. Silver(I) trifluoromethanesulfonate or silver(I) nitrate and a polyimide, derived from 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride and an equimolar amount of 4,4'-oxydianiline and 3,5-diaminobenzoic acid, were dissolved together in dimethylacetamide. Silver(I)-doped films were prepared at thicknesses of 25-40 microm and depleted of solvent by evaporation at ambient temperature and low humidity. The silver(I)-ion-containing films were then treated with aqueous solutions of the reducing agents hydrazine hydrate and hydroxylamine, which brought forth surface-silvered films exhibiting conductivity on the order of bulk polycrystalline silver accompanied by modest-to-high specular reflectivity.

2-aminoethoxydiphenyl borate as a prototype drug for a group of structurally related calcium channel blockers in human platelets.

We have synthesized a series of 2-aminoethoxydiphenyl borate (2-APB, 2,2-diphenyl-1,3,2-oxazaborolidine) analogs and tested their ability to inhibit thrombin-induced Ca(2+) influx in human platelets. The analogs were either synthesized by adding various substituents to the oxazaborolidine ring (methyl, dimethyl, tert-butyl, phenyl, methyl phenyl, and pyridyl) or increasing the size of the oxazaborolidine ring to seven- and nine-membered rings. NMR analysis of the boron-containing analogs suggests that each of them exist as a ring structure through the formation of an N-->B coordinate bond (except for the hexyl analog). The possibility that these boron-containing compounds formed dimers was also considered. All compounds dose-dependently inhibited thrombin-induced Ca(2+) influx in human platelets, with the 2,2-diphenyl-1,3,2-oxazaborolidine-5-one derivative having the weakest activity at 100 microM, whereas the (S)-4-benzyl and (R)-4-benzyl derivatives of 2-APB were approximately 10 times more potent than the parent 2-APB. Two nonboron analogs (3-methyl and 3-tert-butyl 2,2-diphenyl-1,3-oxazolidine) were synthesized; they had approximately the same activity as 2-APB, and this implies that the presence of boron was not necessary for inhibitory activity. All of the compounds tested were also able to inhibit thrombin-induced calcium release. We concluded that extensive modifications of the oxazaborolidine ring in 2-APB can be made, and Ca(2+)-blocking activity was maintained.

Synthesis and photophysical properties of models for twisted PRODAN and dimethylaminonaphthonitrile.

The synthesis and photophysical properties of 7-cyano-3,4-dihydro-2H-1,4-ethano-benzo[g]quinoline and 3,4-dihydro-2H-1,4-ethano-7-propionyl-benzo[g]quinoline are reported. These compounds possess a quinuclidine substructure that locks the tertiary amino group perpendicular to the naphthalene ring. Their excited states are models for the twisted excited states of 2-(dimethylamino)-6-naphthonitrile (DMANN) and 6-propionyl-2-(dimethylamino)naphthlene (PRODAN). In contrast to DMANN and PRODAN, the fluorescence of these twisted derivatives is strongly deactivated in polar solvents. Neither DMANN nor PRODAN likely emit from TICT excited states.