Christopher J. Abelt

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.

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 Ca2+ 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 Ca2+ influx in human platelets, with the 2,2-diphenyl-1,3,2-oxazaborolidine-5-one derivative having the weakest activity at 100 μM, 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 Ca2+-blocking activity was maintained.

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.

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.

Radical cations of cyclopentadiene dimers—facets of an intriguing energy surface

Abstract The radical cations of various cyclopentadiene dimers can be generated by photoinduced electron transfer to strong electron acceptors. Nuclear spin polarization effects observed during these reactions provide insight into the radical cation structures. Three of the systems studied, endo-[4 + 2]-(1), anti-[2+2]-(2), and exo-(4+2]-dicyclopentadiene (5) give rise to unusual singly linked, delocalized radical cations, whereas the anti-[4 + 4]-dimer (3) and 1,3-bishomocubane (4) give rise to more conventional radical cations. The reactions of spiroheptadiene (9) and di(spiroheptadiene) (10) provide evidence for two different dimer radical cations, a doubly linked (D) and a singly linked (S) species. This finding supports a stepwise mechanism for the radical cation Diels-Alder reaction of 9.

Local Solvent Acidities in β-Cyclodextrin Complexes with PRODAN Derivatives

The local solvent acidities (SA scale) of six 6-carbonyl-2-aminonaphthalene derivatives as β-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 host–guest 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.

Investigation of the mercury(II) coordination chemistry of tris[(1-methylimidazol-2-yl)methyl]amine by X-ray crystallography and NMR

The coordination chemistry of Hg(II) with tris[(1-methylimidazol-2-yl)methyl]amine (TMIMA) was investigated. The structures of [Hg(TMIMA)2](ClO4)2 (1), [Hg(TMIMA)(NCCH3)](ClO4)2 (2) and [Hg(TMIMA)Cl]2(HgCl4) (3) were characterized by X-ray crystallography. Complex 1 has six strong Hg–Nimidazoyl bonds ranging from 2.257(5) to 2.631(6) A. Ligand geometry suggests the Hg–N(NR3) distances of 2.959(6) A in 1 reflects weak bonding interactions. This complex has a 199Hg chemical shift of −1496 ppm, significantly upfield from nitrogen coordination complexes with lower coordination numbers. The five-coordinate complex 2 has Hg–N(NR3), Hg–Nimidazoyl and Hg–Nacetonitrile bond lengths of 2.642(8), 2.198(5) and 2.264(11) A, respectively. Complex 3 is also five coordinate, with Hg–N(NR3), Hg–Cl and average Hg–Nimidazoyl distances in the cations of 2.758(7), 2.424(2) and 2.29(4) A, respectively. Conditions for slow exchange on the J(HgH) coupling time-scale were found for both 1 ∶ 1 metal-to-ligand complexes in acetonitrile-d3. Observed heteronuclear coupling constants were similar to those associated with Hg(II) substituted proteins with histidine–metal bonds. Solution and solid-state comparisons to the Hg(II) coordination chemistry of tetradenate pyridyl ligands are made. Relevance to development of 199Hg NMR as a metallobioprobe is discussed.

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 Catalans 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 Catalans 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.

Regioselectivity of the insertion reactions of some aromatic diazo compound complexes with cyclomaltoheptaose

Pyrolysis of solid complexes of aromatic diazo compounds with cyclomaltoheptaose (beta-cyclodextrin) yields either derivatives via insertion of carbene into hydroxyl groups. The distribution of the 2-, 3-, and 6-O-isomers indicates that the regioselectivity is moderate. The guest geometry is not as important as its size in determining the ratios of regioisomers. The origins of the regioselectivity are discussed.

Structure and properties of some cresolphthalein derivatives

Abstract The following cresolphthalein (CP) derivatives are prepared from 5,5′-dibromocresolphthalein (3): 5,5′-dicyano (7), 5,5′-dicarbomethoxy (9); 5-bromo-5′-cyano (8), 5-bromo-5′-carbomethoxy (10), monomethyl ether (11) and 5,5′-dibromo monomethyl ether (13). The lactone ring remains intact in the monobasic forms of 11 and 12. The dibasic forms of the CP derivatives 3 and 8–10 show long-wavelength absorption bands, but exist mainly as the closed lactone structure. The dibasic form of 7 does not show long-wavelength absorption and exists only as the closed lactone structure. The proportion of ring-closed dianion goes as the electron-withdrawing ability of the substituents, and it increases in the order H