Outer Phenyl Rings Research Articles

Generation-Dependent Energy Dissipation in Rigid Dendrimers Studied by Femtosecond to Nanosecond Time-Resolved Fluorescence Spectroscopy

Intramolecular kinetic processes in a series of second-generation polyphenyl dendrimers with multiple peryleneimide chromophores attached to the para position of the outer phenyl ring were investigated by steady-state and femtosecond to nanosecond time-resolved fluorescence spectroscopy. The results obtained were compared to the ones of the corresponding first-generation dendrimer series. The energy-hopping rate constant, khopp, observed from anisotropy decay times was found to be 5 times smaller than that of the first-generation series and scales well with the difference in average distance between the chromophores. In addition to the processes observed in first-generation dendrimers in the ultrafast time domain by fluorescence up-conversion, a second annihilation process is found in the second-generation multichromophoric dendrimer. The observation of two singlet-singlet annihilation processes in this compound can be explained by the presence of a mixture of constitutional isomers leading to a broader distribution of distances between neighboring chromophores compared to first-generation multichromophoric dendrimers.

A Fluorescent 18-Crown-6 Based Luminescence Sensor for Lanthanide Ions

The synthesis and photophysical behavior of a luminescent chemosensor for the early lanthanide elements is described. The sensor is a 1,4-diphenylethynyl-benzene chromophore having 18-crown-6 moieties bound to the outer phenyl rings. The chromophore is luminescent and the emission is quenched by lanthanide (Ln3+) ions with larger ionic radii and existing f–f transitions (Ce3+, Pr3+ and Nd3+). Alkali, alkaline earth ions and lanthanides with smaller radii (Ge3+, Tb3+, Dy3+, and Yb3+) do not affect the emission.

Substituent effects on the electrochemical oxidation ofN,N?,N?-triphenyl-1,3,5-triaminobenzenes

Correlation analysis of the oxidation potentials of a series of N,N′,N″-triphenyl-1,3,5-triaminobenzenes (TPABs) substituted at the para positions of the outer phenyl rings shows a linear free energy relationship with resonance-enhanced substituent parameters (σ+). Reaction parameters (ρ+) for oxidation of TPABs were found to be −1.53, −1.45 and −1.34 (per substituent) in methylene chloride, acetonitrile and propylene carbonate respectively. The resonance enhancement and small magnitude of the ρ+ values are related to a significant but weak delocalization of charge onto the outer phenyl rings in the molecular orbitals of radical cations resulting from the oxidation of TPABs. Data on the oxidation of p-substituted triphenylamines were treated similarly and gave a ρ+ value of −3.27 (per substituent) in acetonitrile, greater than that for TPABs owing to a more significant delocalization of charge onto the phenyl rings in the molecular orbitals of the corresponding radical cations. To demonstrate their predictive value, these linear free energy correlations were used to estimate the oxidation potentials of similarly substituted N,N,N′,N′,N″,N″-hexaphenyl-1,3,5-triaminobenzenes, which are of interest as building blocks for molecular magnetic materials. © 1998 John Wiley & Sons, Ltd.

Inhibition of thyroid hormone uptake by calcium antagonists of the dihydropyridine class.

A series of substituted 4-phenyl-1,4-dihydropyridines 2a-m was tested for their inhibitory effects on L-triiodothyronine (L-T3) uptake by human HepG2 hepatoma cells. The most potent compounds were the nitro-substituted derivatives 2,6-dimethyl-4-(4'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (2m) and the well-known calcium antagonists nitrendipine (2k) and nifedipine (2j) with an uptake inhibition between 80.5 and 85.8% at an application dose of 10(-5) M. On the basis of a theoretical conformational analysis (ab initio MO theory, molecular mechanics, molecular dynamics) of the dihydropyridine derivatives, a unifying stereochemical concept was derived postulating an angular arrangement of the two rings where the phenyl ring of the calcium antagonists, which corresponds to the outer phenyl ring of the thyroid hormones, is bisecting the dihydropyridine ring as a prerequisite for inhibitory potency. This model includes also inhibitors of the N-phenylanthranilic acid type. The interaction of the calcium antagonists with transthyretin (TTR) is discussed in relation to thyroid hormones. The influence of hydrophobicity was estimated by the experimental determination of the 1-octanol/water partition coefficients.

Computer-assisted molecular modeling of benzodiazepine and thyromimetic inhibitors of the HepG2 iodothyronine membrane transporter.

T3 cellular uptake is inhibited in the presence of benzodiazepines (BZs). The structure-activity relationship of BZ inhibition correlates strongly with halogen substitution of the nonfused phenyl ring and indicates that this ring is required for activity. A structure-activity series of thyromimetic (TH) inhibitors of the HepG2 iodothyronine transporter further point out the critical importance of the amino group of the alanine side chain, its L-stereo configuration, and the size of the substituents of the inner and outer phenyl rings. A third series of compounds, reported to interact at related sites, were inactive as HepG2 iodothyronine transport inhibitors, and therefore the potent inhibitors were restricted to the BZ and TH compounds. Using both of these BZ and TH structure-activity series along with computer-assisted molecular modeling techniques, we determined which chemical structural components were important at the transporter interaction site. By superimposing structures from active chemicals, excluding residues from poor inhibitors, and incorporating molecular electropotential data, we developed a five-point model of BZ conformational similarity to the endogenous transporter ligand, L-T3: the alkyl substitution at the N1 of the BZ ring seems to simulate the alanine side chain of T3, and the electro-negative halogen and oxygen atoms of substituents at R3/R7/R2'/R4' of BZ form a pyramidal pharmacophore that seems to correspond with the 3-l/5-l/3'-l/4'-OH substituents of T3, respectively. These points, suggesting a tilted cross-bow formation, may be sites for ligand interaction with the iodothyronine transporter.

Structure of, and internal rotation in, hexakis [4‐(2‐phenylpropan‐2‐yl) phenoxy] benzene, and structural comparison with its precursor phenol 4‐(2‐phenylpropan‐2‐yl)Phenol

AbstractThe title compounds (1 and 3, respectively) were studied by X‐ray crystal structure analysis. Both are trigonal, space group R3, with lattice parameters a = 27.718(6), c = 8.161(2) Å, Z = 3 and a = 31.267(7), c = 6.560(2), Z = 18, respectively. The dodecamethyl compound 1 is isomorphous with its parent hexakis(4‐benzylphenoxy)benzene (2), a known host. However, ‘collapse’ along the c‐axial direction has occurred such that the appreciable clathrate cavity of 2 has been replaced by only a very small residual void for 1. Phenol 3 does not pack in discrete [OH]6 hydrogenbonded hexamers; instead, molecules are assembled in infinite chains, linked by OH…︁O hydrogen bonds of length 2.735(3) Å, which are propagated along threefold screw axes. A variable‐temperature CPMAS NMR study of sidechain aryl group rotation in 1 gives a value ΔG≠ of 14.0 ± 0.7 kcal mol−1 (at 42 °C) for the (crystallographically unique) para ‐disubstituted ring, a similar 14 kcal mol−1 free energy barrier being found hindering rotation of this ring, and of the outer phenyl ring of 1, at 9°C.

HPLC analysis of in vitro hepatic deiodination products of thyroid hormones in the rainbow trout, Oncorhynchus mykiss

Reverse-phase HPLC employing five different solvent systems was used to determine the 125I-labeled products formed in rainbow trout by in vitro incubation at 12° of the hepatic microsome fraction with l-thyroxine (T 4) labeled with 125I in the outer phenyl ring. Trout were starved for 2 weeks or fed a 2% ration. The only labeled products identified during incubation for 7.5–70 min over a T 4 substrate range of 0.03–0.5 n M were 125I − and 3,5,[ 125I]3′-triiodo- l-thyronine (T 3). These products in combination with the parent [ 125I]T 4 accounted for over 96% of the total chromatographic radioactivity. Neither 3,[ 125I]3′-diiodo- l-thyronine nor 3,[ 125I]3′,5′-T 3 (reverse T 3) was detected, suggesting negligible inner-ring deiodination of T 4 or T 3. Essentially equal production of 125I − and [ 125I]T 3 validated the use of 125I − production as a measure of [ 125I]T 3 generation in assays for hepatic 5′-monodeiodinase activity. However, in some experiments the 125I − level slightly exceeded the [ 125I]T 3 level, indicating that outer-ring deiodination of T 3 may occur to a limited degree. In conclusion, the present data for liver support earlier observations from in vivo studies in showing that for trout at 12° deiodination pathways are geared primarily toward T 4 outer-ring monodeiodination to produce T 3 with undetectable inner-ring deiodination of T 3 or T 4 and limited outer-ring deiodination of T 3.

Crystal Structure and Related Properties of Phenothiazine Cation Radical-Hexachloroantimonate. Monoclinic(I) Form

Abstract Three forms of crystals were obtained from mixed solutions of phenothiazine and SbCl5; the crystal structure of the monoclinic(I) modification was determined using 2827 reflections at room temperature. Crystal data: (C12H9NS)+·SbCl6−, F.W.=533.7, monoclinic, a=16.253(3), b=14.334(1), c=15.786(3) Å, β=104.07(1)°, space group C2/c, Dm=2.00, Dx=1.99 g cm−3, Z=8, μ=25.73 cm−1 (Mo Kα). The structure was solved by the heavyatom method and refined by block-diagonal least-squares method to R=0.072. The crystal consists of phenothiazine cation radicals(PT+·) and hexachloroantimonate anions(SbCl6−), and every ion exists as a monomer in the crystal. Each SbCl6− forms a distorted octahedron. The two C–S distances of PT+· are 1.705 and 1.711 Å, and the C–S–C angle is 103.9°. The dihedral angle between the two outer phenyl rings of PT+· is 176.5°. From the ESR measurements of a single crystal, three principal g-values were determined: g1=2.003, g2=2.007 and g3=2.008. The direction of g1 is normal to the molecular plane of PT+·. These facts suggest some π-delocalization in the central ring of PT+·. Absorption spectra polarized parallel to the molecular plane of PT+· are very similar to the poly crystalline reflection spectra of PT+· salts obtained by other authors, and there are no intense bands in the spectra polarized perpendicular to PT+· molecular plane over the wave number range 10 to 27×103 cm−1.

Methyl 3,5-diiodo-4-(3-isopropyl-4-methoxybenzoyl)benzoate

C19 H181204, orthorhombic, Iba2, a = 20.998 (3), b = 24.002 (4), c = 8.032 (1) A, z = 8, M r = 564.2, D c = 1.85 Mg m-3; for 2281 observed data R = 6.6%. The conformation of the diphenyl ketone bridge is skewed and the 3'-isopropyl group distally oriented, as is observed for many thyroid hormone analogue structures. There is a short I...O inter- molecular contact between I(5) and the carbonyl oxygen (3.17 (10) A). Introduction. Structural studies show that the thyroid hormones (Fig. la) are characterized by an oxygen bridging angle of 120 ° and diphenyl ether conforma- tion that is either skewed (i.e. the phenyl ring planes are mutually perpendicular and bisecting) or twist-skewed (Cody, 1980). Either conformation minimizes the steric interactions between the bulky 3,5 inner-ring iodines and the ortho hydrogens of the outer phenyl ring. The observed biological activity and protein-binding affinity of non-oxygen-bridged (S,CH 2) hormone analogues suggests that the requirement for oxygen is not absolute (Jorgensen, 1978). As part of a program to study the effects of oxygen-bridge substitution, as well as to design hormone analogues that could be used as photo affinity probes of hormone-protein binding, a number of carbonyl-bridged thyroid hormone analogues were synthesized and their nuclear receptor protein-binding affinities measured. Here is reported the crystal structure of a ketone-bridged analogue (Fig. l b), which is shown to possess significant nuclear binding affinity (Cheung, unpublished results). Crystals were grown by slow evaporation at room temperature from an ethanol solution. Crystallo- graphic data were measured from a 0.07 × 0.4 × 0.9 mm crystal on a Nicolet P3 automated diffractometer using Nb-filtered Mo Kc~ radiation. Cell dimensions were obtained by a least-squares refinement based on

Molecular conformation of thyroid hormones: structure and binding interactions of thyroxine.

In an accurately determined X-ray diffraction study of the thyroid hormone thyroxine (T4), the two independent conformations in the crystal lattice show significant differences in the outer phenyl ring geometry when compared with that of 3,5,3'-triiodothyronine (T3). The major differences between the T4 and T3 structures are a shortened C4'-O4' bond, contraction of the C3'-C4'-C5' angle and an increase in the C3' and C5' angles of T4. These changes can be correlated with the difference in acidity of the 4'-OH of T4 and T3 and help to explain binding affinity differences among thyroactive compounds. The hydrogen bond directionality observed in T4 and other thyroid structures offers an insight into the molecular details of the hormone-receptor site. The conformation of one T4 molecule is cisoid, that of the other transoid, the first such instance of different overall conformations to be found in the same crystal lattice. One T4 molecule has the side chain nearly coplanar with the inner ring, an unusual conformation among thyroid structures.

Distal conformation of thyroid hormones. Crystal and molecular structure of 3,5,3'-triiodo-L-thyronine methyl ester

In the crystal structure of 3,5,3'-triiodo-L-thyronine methyl ester, the 3' -iodine is distal, i.e., away from the alanine bearing ring, and the overall conformation is cisoid, that is, the alanine moiety and the outer phenyl ring lie on the same side of the inner phenyl ring plane. This conformation, reported here, for the first time, is in contrast to the transoid conformation previously observed for thyroid hormone structures. The torsional angles between the diphenyl either linkages (theta and theta') are -108 and 33 degrees, respectively, while the C-O-C angle is 117 degrees. The value of chi1, which describes the amino acid backbone conformation, is 308 degrees. The structure crystallizes in the tetragonal space group P41 with a = 8.225 (5) and c = 28.42 (1) A. The final R index is 0.06.

A study of π‐conjugation in Chichibabin's ‐ and Schlenk's ‐ like hydrocarbons with ESR: Part i

AbstractAnalysis of the ESR spectrum of the radical cation, derived from p, p′‐bis‐{phenyl(triphenylphosphorylidene)methyl}biphenyl reveals that spin density is found at both 31P nuclei. Zero spin density is indicated for the outer phenyl rings. In the radical cation, derived from the corresponding m,m′‐isomer the spin density is delocalized over one half of the molecule and interaction is found with only one phosphorus atom. In this system the spin density in the outside ring exceeds that in the biphenyl ring. The localization of the odd electron on one half of the molecule must be caused by a strong Jahn‐Teller effect.The assignment of the hyperfine coupling constants was based on spin density calculations according to the Unrestricted Hartree‐Fock (UHF) method. From these calculations we also obtained an indication of the geometry of the radicals.The synthesis of these compounds is reported.

Dynamic Nuclear Polarization by Nitroxide, Perhalocarbon, Semiquinone, and Verdazyl Radicals

Dynamic nuclear polarization has been examined in liquid solutions of 16 different radicals. Hexafluorobenzene was used to gauge the intermolecular hyperfine interaction. The scalar coupling reveals transient complexation between radical and receptor and various bond-forming tendencies. Perhalocarbon radicals show very weak scalar coupling with fluorine nuclei. Verdazyls show strong scalar coupling, with negligible effects from substituents on the outer phenyl rings. Phenoxyl and pyrylyl radicals show a wide range of coupling which is only partly explained by planar complexation. Semiquinones show increasing scalar coupling with increasing chlorination. DNP with aliphatic nitroxide radicals is dominated by the NO group, but aromatic nitroxides show a strong ring substituent effect, exceeding intramolecular hyperfine variation in ESR. It is suggested that DNP can provide unique signatures of substituents on phenyl rings.