Relative basicities of free base porphyrins; understanding the role of macrocyclic distortion

Porphyrins have been the center of numerous investigations in different areas of chemistry, geochemistry, and the life sciences. In nature the conformation of the porphyrin macrocycle varies, depending on the function of its apoenzyme. It is believed that the conformation of the porphyrin ring is necessary for the enzyme to achieve its function and modify its reactivity. It is important to understand how the conformation of the porphyrin ring will influence its properties. ^ In synthetic porphyrins particular conformations and ring deformations can be achieved by peripheral substitution, metallation, core substitution, and core protonation among other alterations of the macrocycle. The macrocyclic distortions will affect the ring current, the ability of pyrroles to intramolecularly hydrogen bond and the relative basicity of each of the porphyrins. To understand these effects different theoretical models are used. The ground state structure of each of 19 free base porphyrins is determined using molecular mechanics (MM+) and semiempirical methods (PM3). The energetics of deformation of the macrocyclic core is calculated by carrying out single point energy calculations for the conformation achieved by each synthetic compound. Enthalpies of solution and enthalpies of protonation of 10 porphyrins with varying degrees of macrocyclic deformation and varying electron withdrawing groups in the periphery are determined using solution calorimetry. Using Hess's Law, the relative basicity of each of the different free base porphyrins is calculated. NMR results are described, including the determination of free energies of activation of ring tautomerization and hydrogen bonding for several compounds. It was found that in the absence of electronic effects, the greater macrocyclic deformation, the greater the basicity of the porphyrins. This basicity is attenuated by the presence of electron withdrawing groups and ability to of the macrocycle to intramolecularly hydrogen bond. ^

Relative basicities of free base porphyrins : understanding the role of macrocyclic distortion

Porphyrins have been the center of numerous investigations in different areas of chemistry, geochemistry, and the life sciences. In nature the conformation of the porphyrin macrocycle varies, depending on the function of its apoenzyme. It is believed that the conformation of the porphyrin ring is necessary for the enzyme to achieve its function and modify its reactivity. It is important to understand how the conformation of the porphyrin ring will influence its properties. In synthetic porphyrins particular conformations and ring deformations can be achieved by peripheral substitution, metallation, core substitution, and core protonation among other alterations of the macrocycle. The macrocyclic distortions will affect the ring current, the ability of pyrroles to intramolecularly hydrogen bond and the relative basicity of each of the porphyrins. To understand these effects different theoretical models are used. The ground state structure of each of 19 free base porphyrins is determined using molecular mechanics (MM+) and semiempirical methods (PM3). The energetics of deformation of the macrocyclic core is calculated by carrying out single point energy calculations for the conformation achieved by each synthetic compound. Enthalpies of solution and enthalpies of protonation of 10 porphyrins with varying degrees of macrocyclic deformation and varying electron withdrawing groups in the periphery are determined using solution calorimetry. Using Hess's Law, the relative basicity of each of the different free base porphyrins is calculated. NMR results are described, including the determination of free energies of activation of ring tautomerization and hydrogen bonding for several compounds. It was found that in the absence of electronic effects, the greater macrocyclic deformation, the greater the basicity of the porphyrins. This basicity is attenuated by the presence of electron withdrawing groups and ability to of the macrocycle to intramolecularly hydrogen bond.

Optimisation de la concentration en électrolytes au sein des matrices à base de HASCA pour la libération prolongée

Le sel sodique du carboxyméthylamidon à haute teneur en amylose, HASCA (Amylose 60%-amylopectine 40%), est un polymère hydrophile ionique utilisé pour obtenir des comprimés matriciels à libération prolongée. Il est caractérisé par la formation d'un hydrogel lors de la mise en contact avec le milieu de dissolution. La libération du principe actif (PA) à travers ce polymère est principalement contrôlée par la diffusion fickienne et la relaxation du réseau polymérique. De plus, la solubilité du PA est un facteur qui permet de moduler la libération, cependant, la solubilité d’un médicament dépend de la forme utilisée et du pH. Les bases ou les acides libres présentent une solubilité moins élevée que leurs sels. Nous proposons d’étudier l’effet d’une combinaison entre le sel et la forme acide ou le sel et la forme alcaline dans le même comprimé matriciel d’HASCA. Comme objectif de ce travail, nous étudions l’influence de la nature du polymère sur le profil de libération de PA dans un milieu aqueux en gradient de pH à cause de la nature des matrices à base d’HASCA caractérisées par la présence de groupement carboxyliques, ionisés ou non selon l’acidité du milieu de dissolution. Nous étudions également l’influence de la nature du PA (base libre ou son sel vs acide libre ou son sel) sur le profil de libération, ceci en sélectionnant des PAs modèles représentatifs de chaque catégorie. L’influence de changement de proportions entre la forme libre (acide ou base) et son sel sur le profil de libération est aussi investiguée. Pour ce, des comprimés à base de HASCA avec des proportions différentes de, soit le naproxène acide et le naproxène de sodium (PA acide et son sel), soit la tétracycline et le chlorhydrate de tétracycline (PA alcalin et son sel) ont été utilisés. Ceux-ci sont évalués lors des tests de dissolution dans un milieu simulant le milieu gastro-intestinal, selon les normes de l’USP (spectrophotométrie UV). Nous avons également menés des études de vitesse de dissolution intrinsèque sur les PAs purs, afin de déterminer leur solubilité et vitesse de libération dans les même pH de dissolution étudiés. Nous avons réussit d’obtenir des comprimés matriciels à base de HASCA convenables à être administrés une fois par jour en utilisant une combinaison du naproxène acide et son sel comme PA. Tandis que les résultats ont montré qu’en utilisant la tétracycline et son sel, les temps de libération étaient trop élevés pour permettre la réalisation d’une formulation convenable pour une administration quotidienne unique

Optical absorption studies of free (H2Pc) and rare earth (RePc) phthalocyanine doped borate glasses

Optical absorption studies of free base and rare earth incorporated phthalocyanine doped borate glass matrix are reported for the first lime. The absorption spectra recorded in the UV- VIS region show two well defined absorption bands of phthalocyanine (Pc) molecule, namely the Soret band (B) and the Q band. The Q band always shows its characteristic splitting in all the doped glass matrices and the intensities of these components are found to vary from one Pc to another. Some of the important optical parameters, namely optical absorption coefficient (a), molar extinction coefficient (ε), absorption cross section (σa), oscillator strength (f), electric dipole strength (q2), absorption half bandwidth (Δλ) of the principal optical transitions have also been evaluated. Moreover, the spectral dependence of refractive index (n) and thereby the optical dielectric constant (ε) on wavelength yielded values of carrier concentration to effective mass ratio (N/m*) of the phthalocyanine molecule in the present glassy systems. Optical band gap (Eg) and width of the band tail (Et) are computed and their variations among the prepared samples are also discussed.

Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.

Metal-centred versus ligand-centred luminescence quenching of a macrocyclic copper(II) complex

The new macrocyclic ligand trans-6-(9-anthracenylmethylamino)-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecan-13-amine has been synthesized and characterised as its copper(II) complex and the crystal structure of this complex has been determined. Fluorescence of the anthracenyl group of the macrocycle is quenched in its free base form and when complexed with Cu-II. Fluorescence returns when Lewis acids such as H+ and Zn-II are added to solutions of the ligand, indicating that photoinduced electron transfer from the amine lone pairs is responsible for fluorescence quenching in the free base form. By contrast, fluorescence of the complex is quenched by intramolecular electronic energy transfer.

Tetra-crowned porphyrin as P450 biomimetic model for carbamazepine oxidation

A substituted porphyrin bearing four crown ether units, H(2)(TCP), was synthesized from the reaction between (5,10,15,20-tetra(o-aminophenyl) porphyrin) and the acyl derivative of the ether (4-carboxy-18-crown-6). The free-base porphyrin was characterized by C, N, and H elemental analysis; UV-vis and IR spectroscopies; and (1)H NMR. The corresponding ironporphyrin, Fe(TCP)Cl, was obtained via iron insertion into H(2)(TCP). Fe(TCP)Cl was employed as catalyst for carbamazepine (CBZ) oxidation by iodosylbenzene (PhIO), 3-chloroperoxybenzoic acid (m-CPBA) or sodium hypochlorite (NaOCl), in methanol or in a biphasic water/dichloroethane system. The crowned ironporphyrin proved to be a highly efficient and selective catalyst for CBZ epoxidation even in the biphasic dichloroethane /H(2)O system, with no need for an additional phase transfer agent.

Photoinduced electron transfer and electronic energy transfer in naphthyl-appended cyclams

A series of novel macrocyclic tetraaza ligands that incorporate a naphthalene moiety as a photoactive chromophore have been prepared and structurally characterized as their Cu(II) complexes. Variable-temperature photophysical studies have concluded that the luminescence quenching evident in the Cu(H) complexes is due to intramolecular electronic energy transfer (EET). In their free-base forms, these ligands undergo reductive luminescence quenching via photoinduced electron transfer (PET) reactions, with proximate amine lone pairs acting as electron donors. Consequently, the emission behavior can be modulated by variations in pH and/or the presence of other Lewis acids such as Zn(H).

Intramolecular electronic energy transfer in bichromophoric macrocyclic complexes

Efficient intramolecular electronic energy transfer (EET) has been demonstrated for three novel bichromophoric compounds utilizing a macrocyclic spacer as the bridge between the electronic energy donor and acceptor fragments. As their free base forms, emission from the electronically excited donor is absent and the acceptor emission is reductively quenched via photoinduced oxidation of proximate amine lone pairs. As their Zn(II) complexes, excitation of the donor results in sensitization of the electronic acceptor emission.

Pyridyyliryhmän sisältävien erotusmateriaalien ominaisuudet ja soveltaminen hydrometallurgiassa

Diplomityössä tutkittiin silikarunkoisen, pyridyyliryhmän sisältävän erotusmateriaalin kykyä erottaa selektiivisesti kuparia, nikkeliä, kobolttia ja kadmiumia sinkkisulfaattiliuoksista. Erotuskykyä verrattiin kolonnikokein toiseen kaupalliseen polystyreenidivinyylibentseenirunkoiseen (PS-DVB) erotusmate-riaaliin, jonka funktionaalinen ryhmä on samantyyppinen. Silikarunkoisen erotusmateriaalin happo-emäsominaisuuksia selvitettiin titrauksin. Metallien sitoutumisen kinetiikkaa ja eluointia verrattiin PS-DVB-runkoisen erotus-materiaalin kirjallisuudessa esitettyihin tuloksiin. Lisäksi määritettiin kummankin erotusmateriaalin partikkelikokojakaumat. Silikarunkoisen materiaalin havaittiin turpoavan noin 4 % muutettaessa se vapaastaemäsmuodosta happomuotoon. Turpoaminen oli huomattavasti vähäisempää kuin PS-DVB-runkoisella materiaalilla. Silikarunkoisen erotus-materiaalin titrauksen tuloksena voitiin todeta, että se oli heikosti emäksinen. Titrauskäyrä muistutti PS-DVB-runkoisen erotusmateriaalin titrauskäyrää, vaikka erotusmateriaalien protonoitumisalueet olivat hieman erilaiset. Tämä johtuu siitä, että silikarunkoisen materiaalin funktionaaliset ryhmät poikkeavat rakenteeltaan hieman PS-DVB-runkoisesta materiaalista. Tasapainokokeet osoittivat, että silikarunkoinen erotusmateriaali adsorboi tutkituista metalleista eniten kuparia ja nikkeliä ja vähiten sinkkiä. Kaikkien tutkittujen metallien eluointi silikarunkoisesta erotusmateriaalista onnistui rikkihapolla toisin kuin PS-DVB-runkoisesta erotusmateriaalista, jonka regenerointiin tarvitaan rikkihappoa tai ammoniumhydroksidia riippuen siitä, mitä metalleja siihen on ladattu.

A time-resolved electron paramagnetic resonance spectroscopy study of paramagnetic porphyrins /

There is considerable interest in intramolecular energy transfer, especially in complexes which absorb visible light, because it is crucial to the better understanding of photoharvesting systems in photosynthetic organisms and for utilizing solar energy as well. Porphyrin dimers represent one of the best systems for the exploration of light-induced intramolecular energy transfer. Many kinds of porphyrins and porphyrin dimers have been studied over the past decade, however little attention has been paid to the influence of paramagnetic metals on the behavior of their excited states. In this thesis, Electron Paramagnetic Resonance Spectroscopy (EPR) is used to study such compounds. After light irradiation, porphyrins easily produce a variety of excited states, which are spin polarized and can be detected by the time-resolved (TR) EPR technique. The spin polarized results for vanadyl porphyrins, their electrostatically-coupled dimers, a covalently-linked copper porphyrin-free base porphyrin dimer, and free base porphyrins are presented in this thesis. From these results we can conclude that the spin polarization patterns of vanadyl porphyrins come primarily from the trip-quartet state generated by intersystem crossing (lSC) from the excited sing-doublet state through the trip-doublet state. The spin polarization pattern of electrostatically-coupled vanadyl porphyrin-free base porphyrin dimer is produced by the triplet state of the free base porphyrin half which is coupled to the unpaired electron on the vanadyl ion.