Thermal relaxation of poled non-linear optical sidechain polymers: A new,semi-empirical model

Electro-Optic relaxation of a poled, Non-Linear Optical sidechain polymer with T_g 140°C, containing 4-dimethylamino-4′-nitrostilbene (“DANS”) in the sidechains, has been studied at 120°C with and without annealing at the same temperature. The time-dependence of the decaying EO coefficients r(t) shows a strong departure from the classical single-exponential Debye model, especially in the unannealed samples. This departure is attributed to physical ageing, slowing down the orientational relaxation of the sidechains. The Debye model with r(t)-r(0). exp -t/τ] is modified semi-empirically by introducing a time-dependent characteristic Debye relaxation time τ(t). Of several trial expressions, one is selected which fits the relaxation data. This is τ(τ)-τ_i+C.t^b     

Une nouvelle méthode numérique de détermination parspectrophotométrie de constantes d'ionisation sechevauchant

A new method of calculation has been developed to obtain two pK_a values from spectrophotometric data in cases when the values are so close together that the calculations usually applied for individual pK_a values are not appropriate. This technique, in which all the experimental data are used to solve for absorbance of monoprotonated species, pK_a1 and pK_a7 by a “complex” method of optimization, is more general than the classical least-squares method. An application is described.     

Calculation of amino acid pKaS in a protein from a continuum electrostatic model: Method and sensitivity analysis

We used continuum electrostatic theory to calculate pK_as of amino acids in protein. A Green's function formalism, based on a finite-difference solution to the Poisson–Boltzmann equation for a unit point charge, yields electrostatic potentials that allow calculation of amino acid pK_as to an estimated accuracy of tenths of a pK_a unit. Improvements over previous methods include the ability to focus the finite difference grid to arbitrarily small grid spacing, an analytical representation of the molecular surface, and a novel procedure to calculate the reaction field potential. Using this method, we performed a sensitivity analysis of calculated pK_as in the photosynthetic reaction center. Calculated pK_as are most sensitive for residues that are not well-exposed to solvent. Variations in the parameters of the continuum electrostatic model cause pK_a shifts that are larger than the accuracy of the numerical method, but probably not large enough to account for some of the discrepancies between calculated and experimentally measured pK_as that have been reported for the reaction center. © 1996 by John Wiley & Sons, Inc.     

Beiträge zur Chemie der Pyrrolpigmente, 51. Mitt.: Phytochrommodellstudien: Zur Deprotonierung von 3,4-Dihydropyrromethenonen und 2,3-Dihydrobilatrienen-abc

3,4-Dihydropyrromethenones and 2,3-dihydrobilatrienes-abc are deprotonated with a characteristicpK _a value of about 11–12 at the NH of the saturated lactam ring. This deprotonation step depends on the availability of stabilisation by hydrogen bonding and charge delocalisation. This was deduced bypK _a measurements of 20 derivates bearing methyl groups at certain N-positions to block deprotonation selectively. Moreover, a¹H-NMR shift criterion was established to detect the deprotonation site. Fluorescence data are given for several 2,3-dihydrobilatrienes-abc; a crossover of relative acidity and basicity in the excited state was observed in the case of a “normal” 2,3-dihydrobilatriene-abc by applying aFörster cycle.     

Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5

The structure of MoeN5, a unique prenyltransferase involved in the biosynthesis of the antibiotic moenomycin, is reported. MoeN5 catalyzes the reaction of geranyl diphosphate (GPP) with the cis‐farnesyl group in phosphoglycolipid 5 to form the (C₂₅) moenocinyl‐sidechain‐containing lipid 7 . GPP binds to an allylic site (S1) and aligns well with known S1 inhibitors. Alkyl glycosides, glycolipids, can bind to both S1 and a second site, S2. Long sidechains in S2 are “bent” and co‐locate with the homoallylic substrate isopentenyl diphosphate in other prenyltransferases. These observations support a MoeN5 mechanism in which 5 binds to S2 with its C6–C11 group poised to attack C1 in GPP to form the moenocinyl sidechain, with the more distal regions of 5 aligning with the distal glucose in decyl maltoside. The results are of general interest because they provide the first structures of MoeN5 and a structural basis for its mechanism of action, results that will facilitate the design of new antibiotics.     

A Novel QSAR Approach for Estimating Toxicity of Phenols

Abstract

Toxicity values (log IGC^?1 ₅₀) for 60 phenols tested in the 2-d static population growth inhibition assay with the ciliate Tetrahymena pyriformis were tabulated. Each chemical was selected so the series formed uniform coverage of the hydrophobicity/ionization surface. A high quality hydrophobicity-dependent (log K _ow) structure-toxicity relationship (log IGC^?1 ₅₀ = 0.741 (log K_ow) ?1.433; n = 17; r² = 0.970; s = 0.134; F = 486.55; Pr > F = 0.0001) was developed for phenols with pK_a values > 9.8. Similarly, separate hydrophobicity-dependent relationships were developed for phenols with pK_a values of 4.0, 5.1, 6.3, 7.5, and 8.7. Comparisons of intercepts and slopes, respectively, revealed phenols with pK_a values of 6.3 to be the most toxic and the least influenced by hydrophobicity. These relationships were reversed for the more acidic and basic phenols. Plots of toxicity versus pK_a for nitro-substituted phenols and phenols with log K_ow values of either 1.75 or 2.50 further demonstrated bilinearity between toxicity and ionization. In an effort to more accurately model the relationship between toxicity and ionization, the absolute value function |6.3-pK_a| was used to model ionization affects for derivatives with pK_a values between 0 and 9.8. For derivatives with pK_a value > 9.8, a value of 3.50 was used to quantitate ionization effects. The use of log K_ow in conjunction with this modified pK_a (ΔpK_a) resulted in the structure-toxicity relationship (log IGC^?1 ₅₀ = 0.567 (log K_ow)-0.226 (ΔpK_a-0.079; n = 54; r² = 0.926; s = 0.215; F = 321.06; Pr > F = 0.0001). Derivatives with a nitro group in the 4-position typically did not model well with the above equation.     

Simple methods for the estimation of ionization constants of substituted pyridine N-oxides in polar aprotic solvents and water

A direct method for the determination of the pK _a values of acids conjugated to substituted pyridine N-oxides has been proposed which is based on the pH measurement of the solution of the basic salt. It has been experimentally shown that the method is reliable when applied to N-oxides of not too low basicity (pK _a >5). Correlation has been performed between the pK _a values in aqueous and aprotic media solutions which shows the great influence of the solvation effect on the acid-base equilibria. The good correlation between the pK _a values in aqueous and non-aqueous solutions enables the pK _a values in water to be estimated with sufficient accuracy, even in the cases when the experimental limitations make the determination impossible which is shown on the basis of selected examples.     

Thermodynamic dissociation constants of silychristin, silybin, silydianin and mycophenolate by the regression analysis of spectrophotometric data

Mixed dissociation constants of four drug acids, i.e. silychristin, silybinin, silydianin and mycophenolate at various ionic strengths I of range 0.01 and 0.30 and at temperatures of 25 and 37 °C were determined using the SQUAD(84) regression analysis program applied to pH-spectrophotometric titration data. The proposed strategy of an efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of silychristin. The thermodynamic dissociation constant pK_a^T was estimated by non-linear regression of {pK_a, I} data at 25 and 37 °C: for silychristin pK_a,1^T=6.52(16) and 6.62(1), pK_a,2^T=7.22(13) and 7.41(5), pK_a,3^T=8.96(9) and 8.94(9), pK_a,4^T=10.17(7) and 10.03(8), pK_a,5^T=11.89(4) and 11.63(7); for silybin pK_a,1^T=7.00(4) and 6.86(5), pK_a,2^T=8.77(11) and 8.77(3), pK_a,3^T=9.57(8) and 9.62(1), pK_a,4^T=11.66(3) and 11.38(1); for silydianin pK_a,1^T=6.64(7) and 7.10(6), pK_a,2^T=7.78(5) and 8.93(1), pK_a,3^T=9.66(9) and 10.06(11), pK_a,4^T=10.71(7) and 10.77(7), pK_a,5^T=12.26(5) and 12.14(5); for mycophenolate pK_a^T=8.32(1) and 8.14(1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of parameter estimates to be found.     

The deprotonation and protonation equilibria of a hypericin derivative in aqueous solution

Summary A hypericin derivative ,'-appended at the methyl groups with two polyethylene glycol moieties (about 23 units long) and capped with acetyl groups was synthesized starting from emodin. This derivative proved to be soluble in water and was investigated by means of spectrophotometric titrations and electrophoresis experiments. Deprotonation at thebay-region hydroxyl group was observed atpK _a=1.6. This was followed by a second deprotonation step of aperi-hydroxyl group at apK _a value of 9.4. This derivative could be protonated at the carbonyl group characterized by apK _a value of –5.7. FrompK _a determinations in water-ethanol mixtures the correspondingpK _a values of hypericin itself determined in such mixtures were extrapolated to the aqueous phase. This resulted in estimatedpK _a values of 1.8, 9.2, and –6.

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Deprotonierungs- und Protonierungsgleichgewichte eines Hypericinderivates in wäßriger Lösung

Zusammenfassung Ein an den Methylgruppen von Hypericin mit endständig acetylierten Polyethylenglykolketten (ungefähr 23 Einheiten lang) ,'-disubstituiertes Derivat wurde ausgehend von Emodin synthetisiert. Dieses Derivat ist wasserlöslich, und es wurde mit Hilfe von spektrophotometrischen Titrationen und Elektrophorese untersucht. Die Deprotonierung derbay-Hydroxylgruppe erfolgt beipK _a=1.6. Diese wird von einem zweiten Deprotonierungsschritt an einerperi-Hydroxylgruppe bei einempK _a-Wert von 9.4 gefolgt. Dieses Derivat konnte an der Carbonylgruppe protoniert werden, was durch einenpK _a-Wert von –5.7 charakterisiert ist. Ausgehend vonpK _a-Messungen in Wasser-Ethanol-Mischungen wurden die entsprechendenpK _a-Werte auch für das Hypericin selbst in wäßriger Phase extrapoliert. Dies führte zu geschätztenpK _a-Werten von 1.8, 9.2 und –6.

     

The Protonation and Deprotonation Equilibria of Hypericin Revisited

 The protonation and deprotonation behaviour and the assignment of pK _a values of hypericin are reviewed and discussed. Three experiments (electrospray MS, ¹H NMR, acid–base indicator equilibria) provided additional evidences for the assignment of pK _a values of −5 and −6 to mono- and diprotonation at the carbonyl groups of hypericin, of pK _a = 2 to monodeprotonation at the bay-region, and of pK _a = 11 to dideprotonation at the bay- and peri-regions.     

Reaktivität der Pyrrolpigmente, 2. Mitt.: Deprotonierung von 3-Pyrrolin-2-onen

Deprotonation of 3,4-dimethyl-3-pyrrolin-2-on (1) int-butyl alcohol/potassiumt-butoxide solutions takes place on the N atom, as shown by¹H/²H exchange andpK _a determinations of1 (pK=17.1), 1,3,4-trimethyl-3-pyrrolin-2-one (pK _a =17.6), and 3,4-dimethyl-5-methoxy-2_H-pyrrole (pK _a =16.7). The SCF-MO approximation MINDO/3 indicates, however, that in the gas phase deprotonation of1 should occur at the C atom.

1.Mitt.:Ribó, J. M., Trull, F., Mh. Chem.110, 201 (1979).     

Incorporating solvation effects into density functional theory: Calculation of absolute acidities

An approach to the calculation of molecular electronic structures, solvation energies, and pK_a values in condensed phases is described. The electronic structure of the solute is described by density functional quantum mechanics, and electrostatic features of environmental effects are modeled through external charge distributions and continuum dielectrics. The reaction potential produced by a mode of the molecular charge distribution is computed via finite-difference solutions to the Poisson-Boltzmann equation and incorporated into the self-consistent field procedure. Here we report results on three sets of organic acids, whose pK_a values range over 16 pH units. The first set provides models for ionizable side chains in proteins; the second set considers the effects of substituting one to three chlorine atoms for hydrogens in acetic acid; and the final set consists of 4-substituted-bicyclo-[2.2.2]-octanecarboxylic acids. Successful prediction of “absolute” pK_a values places stringent requirements on the computation of gas-phase proton affinities and on the response to solvation. In some cases the current model shows substantial errors, but overall the results and trends are in good agreement with experiment. Prospects for extending this approach to more complex systems such as proteins are briefly discussed. © 1997 John Wiley & Sons, Inc.     

Kinetics of the formation and hydrolysis of the schiff's base of 4-pyridinecarboxaldehyde with N-hexylamine in water-dioxan mixtures

We have carried out a kinetic study of the 4-pyridinecarboxaldehyde plus n-hexylamine system, at 25°C, in water-dioxan mixtures (0–60% v/v) and in the pH range pK_a + 1.5 > pH > pK_a ? 1.5, where pK_a is the pK value of the conjugate acid of the amine. The results obtained could be interpreted in terms of a rate constant for Schiff's base hydrolysis and a rate constant for the reaction between the nonprotonated n-hexylamine and the nonhydrated form of 4-pyridinecarboxaldehyde. Both constants decrease sharply as the dioxan content of the solvent increases, in a manner consistent with Marshall's model [J. Phys. Chem., 74 , 346 (1970)]. It is suggested that the transition state of the rate-limiting step (carbinolamine dehydration) is highly solvated by water molecules and has a high separation of charges.     

The Protonation and Deprotonation Equilibria of Hypericin Revisited

Summary.  The protonation and deprotonation behaviour and the assignment of pK _a values of hypericin are reviewed and discussed. Three experiments (electrospray MS, ¹H NMR, acid–base indicator equilibria) provided additional evidences for the assignment of pK _a values of −5 and −6 to mono- and diprotonation at the carbonyl groups of hypericin, of pK _a = 2 to monodeprotonation at the bay-region, and of pK _a = 11 to dideprotonation at the bay- and peri-regions. Received September 26, 2001. Accepted October 1, 2001     

The thermodynamic dissociation constant of naphazoline by the regression analysis of potentiometric data

The mixed dissociation constant of naphazoline is determined at various ionic strengths I [mol dm⁻³] in the range of 0.01 to 0.26 and at temperatures of 25°C and 37°C using ESAB and HYPERQUAD regression analysis of the potentiometric titration data. A strategy of efficient experimentation is proposed in a protonation constant determination, followed by a computational strategy for the chemical model with a protonation constant determination. Two group parameters, L ₀ and H _T were ill-conditioned in the model and their determination is therefore uncertain. These group parameters, L ₀ and H _T, can significantly influence a systematic error in the estimated common parameter pK_a and they always should be refined together with pK _a. The thermodynamic dissociation constant pK _a^T was estimated by nonlinear regression of {pK _a, I} data at 25°C and 37°C: for naphazoline pK _al^T = 10.41(1) and 10.13(2). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found.      

EXCITED STATES OF SIX-MEMBERED N-HETEROCYCLES. FLUORESCENCE, PHOSPHORESCENCE AND ACID—BASE EQUILIBRIA OF ELECTRONICALLY EXCITED PHENAZINE

Abstract— An account of a systematic study of the acid-base equilibria of phenazine in the two lowest excited (π,π) states is presented. Pure electronic levels of the free base and of both its protonated forms have been located by spectroscopic methods. Fluorescence, phosphorescence and corresponding absorption spectra have been measured. The O-O energies of the free base, of the singly-protonated species and of the doubly protonated form in the lowest triplet state (³L_α(π, π)) are: 15, 475 cm^-1, 14, 175 cm^-1 and about 9300cm^-1, respectively. This last value has been estimated from the experimentally determined S-T splitting in the other two forms. Corresponding energies of the lowest singlet state (^IL_α(π,π)) are: 23,500 cm^-1, 21,250cm^-1 and 17,300 cm^-1. The fluorescence of the free base has been found in polar as well as in non-polar solvents and has been checked by the fluorescence excitation spectrum. Fluorescence quantum yields for the free base have been measured: 8.6 times 10^-4 and 3.0 × 10^-5 in ethanol and hexane solutions, respectively. Emission in ethanol has been ascribed to (π,π), that in hexane —to (π, π). fluorescence. The changes of pK_α's under excitation, calculated from the Forster's cycle, are equal: δpK_a¹=+2.8±0.3; δpK_a¹¹?+10±1.5 in the lowest (π, π) triplet state and δpK_a¹=+4.8±0.5; δpK_a¹¹=+8.4 ± 0.5 in the lowest (π,π) singlet state. The δpK_a¹¹ in the triplet state is at least as high as that in the ¹L_a(π, π) state. P P P calculations of the electronic levels and of the molecular diagrams have been performed. The energies obtained exceed experimental values by not more than 0.5 eV. An increase of the net charge on nitrogen δp under excitation has been found to be +50, +70 and +19 per cent in the ¹L_a, ¹L_b and ³L_a states, respectively. A good correlation has been found between δpK_a¹ and δp in both excited states, which have been studied experimentally.     

On the synthesis of hypericin by oxidative trimethylemodin anthrone and emodin anthrone dimerization: Isohypericin

Summary The base catalyzed oxidative dimerization of emodin anthrone exclusively yields hypericin. However, on oxidative dimerization of trimethylemodinanthrone a mixture of hexamethylhypericin and hexamethylisohypericin was obtained. Chromatographic separation of the hexabenzoyl derivatives was achieved, and by saponification about equal amounts of hypericin and isohypericrin were produced. Isohypericin could be characterized for the first time by its spectroscopic data and its protonation and deprotonationpK _a andpK _a ^* values.

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Zur Synthese von Hypericin durch oxidative Dimerisierung von Trimethylemodinanthron und Emodinanthron: Isohypericin

Zusammenfassung Die basenkatalysierte oxidative Dimerisierung von Emodinanthron liefert ausschließlich Hypericin. Oxidative Dimerisierung von Trimethylemodinanthron ergibt jedoch ein Gemisch von Hexamethylhypericin und Hexamethylisohypericin. Die Hexabenzoylderivate wurden chromatographisch getrennt, und Hypericin und Isohypericin konnten aus diesen Derivaten durch Verseifung freigesetzt werden. Isohypercin konnte erstmals durch seine spektroskopischen Daten und seine Protonierungs- und Deprotonierungs-pK _aundpK _a ^* -Werte charakterisiert werden.

     

Spectrophotometric determination of the acid dissociation constants for cacodylic acid and p-Nitrophenol at elevated temperatures

Using 2.5-dinitrophenol as an optical indicator, the pK_a of cacodylic acid were spectrophotometrically determined at elevated temperatures under saturation vapor pressures. The result is pK_a = -26.41 + 1296/T + 4.973 InT whereT is in Kelvin. In a similar way, the pK_a ofp-nitrophenol were obtained up to 200‡C giving pK_a = -24.82 + 2135/T + 4.353 InT From these results, several thermodynamic functions of cacodylic acid andp- nitrophenol were calculated.     

Theoretical pKa calculations of proteins; the tyrosine and lysine residues of b-elicitin

Elicitins are small proteins that are secreted by plant pathogenic fungi. In this work we have used a computer program that utilizes the boundary element method for heterogeneous dielectrics with ionic strength to calculate the pK _a of all titrating groups in the 98-residue protein β-cryptogein. Our results are in reasonable agreement with the experimentally determined pK _a values for the Tyr residues in the protein. We find that the functionally important Lys13 residue has a normal pK _a of 10.3. Our work also shows that there is no direct correlation between the exposure of an amino acid sidechain and its pK _a. Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 11 November 1998     

Concerning the absorption and emission properties of phenanthro[1,10,9,8,o,p,q,r,a]perylene-7,14-dione

Summary In contrast to hitherto published data, phenanthro[1,10,9,8,o,p,q,r,a]perylene-7,14-dione, the fundamental chromophoric system of hypericin type compounds, exhibits an absorption with a long wavelength band at 423 nm in aprotic solvents like dimethylsulfoxide (7000). Its fluorescence in these solvents is below the detection limit. In protic solvents like methanol, the long wavelength absorption is bathochromically shifted to 546 nm, and a fluorescence at 565 nm is observed. This behavior was interpreted from the reversal ofn – * and – * transitions. The data have not been recorded yet due to the very low solubility of this compound. Its monoprotonation in ground and excited states is characterized bypK _a andpK* _a values of –6 and 2; diprotonation occurs at apK _a=–7.

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Absorptions- und Emissions-Eigenschaften von Phenanthro[1,10,9,8,o,p,q,r,a]perylen-7,14-dion (Kurze Mitt.)

Zusammenfassung Im Gegensatz zu bislang publizierten Daten zeigt Phenanthro[1,10,9,8,o,p,q,r,a]perylen-7,14-dion, das fundamentale chromophore System der Hypericintyp-Verbindungen, in aprotischen Lösungsmitteln wie Dimethylsulfoxid eine Absorption mit einer langwelligen Bande bei 423 nm (7000). In diesen Lösungsmitteln ist Fluoreszenz nicht nachweisbar. In protischen Lösungsmitteln wie Methanol wird die langwellige Bande bathochrom verschoben (546 nm) und bei 565 nm tritt Fluoreszenz auf. Dieses Verhalten wurde mit der Umkehr in der Reihenfolge vonn – * und – * Übergängen interpretiert. Die Daten wurden wegen der extremen Schwerlöslichkeit dieser Verbindung bislang nicht erhalten. Die Monoprotonierung im Grund- und Anregungszustand ist durchpK _a- undpK* _a -Werte von –6 und 2 charakterisiert; die Diprotonierung tritt beipK _a=–7 ein.