Model systems for flavoenzyme activity: relationships between cofactor structure, binding and redox properties

A series of flavins were synthesized bearing electron-withdrawing and -donating substituents. The electrochemical properties of these flavins in a nonpolar solvent were determined. The recognition of these flavins by a diamidopyridine (DAP) receptor and the effect this receptor has on flavin redox potential was also quantified. It was found that the DAP-flavin binding affinity and the reduction potentials (E(1/2)) for both the DAP-bound and unbound flavins correlated well with functions derived from linear free energy relationships (LFERs). These results provide insight and predictive capability for the interplay of electronics and redox state-specific interactions for both abiotic and enzymatic systems.     

A mathematical model for pollution in a river and its remediation by aeration

We present a simple mathematical model for river pollution and investigate the effect of aeration on the degradation of pollutant. The model consists of a pair of coupled reaction–diffusion–advection equations for the pollutant and dissolved oxygen concentrations, respectively. The coupling of these equations occurs because of reactions between oxygen and pollutant to produce harmless compounds. Here we consider the steady-state case in one spatial dimension. For simplified cases the model is solved analytically. We also present a numerical approach to the solution in the general case. The extension to the transient spatial model is relatively straightforward. The study is motivated by the crucial problem of water pollution in many countries and specifically within the Tha Chin River in Thailand. For such real situations, simple models can provide decision support for planning restrictions to be imposed on farming and urban practices.     

An oxo‐bridged centrosymmetric tetranuclear titanium compound

The title compound, octa‐tert‐butoxybis­[μ₃‐2,2′‐(N‐methyl­imino)­diethanolato]­di‐μ‐oxo‐tetratitanium(IV), [Ti₂O{(OCH₂CH₂)₂(NCH₃)}{(CH₃)₃CO}₄]₂ or [Ti₄(C₅H₁₁NO₂)₂(C₄H₉O)₈O₂], lies about an inversion centre, and displays the less usual zigzag configuration. One O atom of the N‐methyl­diethoxo­amine ligand bridges the symmetry‐related Ti atoms, while the other bridges the two independent Ti atoms, with the N atom binding to give a facial configuration. Four ^tBuO⁻ ligands and a bridging oxide complete the respective five‐ and sixfold coordination of the two Ti atoms. The Ti—O bond lengths range in a self‐consistent fashion from 1.7624 (17) to 2.0878 (18) Å, while the Ti—N bond length is 2.374 (2) Å.     

{N‐[2‐(η5‐Cyclopentadienyl)ethyl]‐4‐toluenesulfonamido‐N,O}(tetrahydrofuran‐O)bis(trifluoromethanesulfonato‐O)titanium(II)

The title compound, [Ti(CF₃O₃S)₂(C₁₄H₁₅NO₂S)(C₄H₈O)], contains a unique ligand system in which the Ti ion is bound to the N and O atoms of a 2‐p‐toluene­sulfon­amide ligand, which is linked by an ethyl group to a coordinated cyclo­penta­diene moiety. The distorted octahedral geometry about the Ti ion is completed by two tri­fluoro­methane­sulfonate ligands and a tetra­hydro­furan mol­ecule. Comparison with related compounds shows that both the Ti—N and Ti—O bonds of the sulfon­amide, although longer than normal values, indicate significant bonding interactions.     

Exciplex Formation and Excited State Deactivation of Difluoroborondipyrromethene (Bodipy) Dyads

Two series of geometrically‐related dyads are discussed based on the difluoroborondipyrromethene (Bodipy) unit, and incorporating covalently attached hydroquinone/quinone groups. These units are anchored directly, or via a phenylene spacer, to the Bodipy core at the meso position in one series ( BD‐MHQ , BD‐MQ , BD‐MPHQ , BD‐MPQ ), but for the second series the attachment site is the 2‐position ( BD‐SHQ , BD‐SQ , BD‐SPHQ , BD‐SPQ ). The compounds show various levels of fluorescence depending on the oxidation state of the appended group and the substitution pattern. In non‐polar solvents such as toluene, diethyl ether and dichlorobenzene, the S₁ state deactivation of the Bodipy unit in BD‐SPQ and BD‐MPQ is dominated by ^{1, 3}exciplex formation, which has not been reported for Bodipy derivatives so far. In the latter molecule, the decay of the exciplex is divided between population of the Bodipy triplet state (13 %–21 %) and ground state reformation. This partitioning is not seen for the side‐on substituted derivative, BD‐SPQ , and only ground state reformation is observed following decay of the exciplex. This difference in behavior is explained by the radical‐pair inter‐system‐crossing mechanism, which more effectively operates in BD‐MPQ because of the orthogonality of the donor‐acceptor units. In the more polar solvent CH₃CN all the quinone derivatives show fast formation of the charge‐separated state (k_CS) followed by slower charge recombination (k_CR). The ratio k_CS/k_CR≤80.     

A study into the effect of subtle structural details and disorder on the terahertz spectrum of crystalline benzoic acid

The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.     

Water-enhanced low-temperature CO oxidation and isotope effects on atomic oxygen-covered Au(111)

Water-oxygen interactions and CO oxidation by water on the oxygen-precovered Au(111) surface were studied by using molecular beam scattering techniques, temperature-programmed desorption (TPD), and density functional theory (DFT) calculations. Water thermally desorbs from the clean Au(111) surface with a peak temperature of approximately 155 K; however, on a surface with preadsorbed atomic oxygen, a second water desorption peak appears at approximately 175 K. DFT calculations suggest that hydroxyl formation and recombination are responsible for this higher temperature desorption feature. TPD spectra support this interpretation by showing oxygen scrambling between water and adsorbed oxygen adatoms upon heating the surface. In further support of these experimental findings, DFT calculations indicate rapid diffusion of surface hydroxyl groups at temperatures as low as 75 K. Regarding the oxidation of carbon monoxide, if a C (16)O beam impinges on a Au(111) surface covered with both atomic oxygen ( (16)O) and isotopically labeled water (H 2 (18)O), both C (16)O (16)O and C (16)O (18)O are produced, even at surface temperatures as low as 77 K. Similar experiments performed by impinging a C (16)O beam on a Au(111) surface covered with isotopic oxygen ( (18)O) and deuterated water (D 2 (16)O) also produce both C (16)O (16)O and C (16)O (18)O but less than that produced by using (16)O and H 2 (18)O. These results unambiguously show the direct involvement and promoting role of water in CO oxidation on oxygen-covered Au(111) at low temperatures. On the basis of our experimental results and DFT calculations, we propose that water dissociates to form hydroxyls (OH and OD), and these hydroxyls react with CO to produce CO 2. Differences in water-oxygen interactions and oxygen scrambling were observed between (18)O/H 2 (16)O and (18)O/D 2 (16)O, the latter producing less scrambling. Similar differences were also observed in water reactivity toward CO oxidation, in which less CO 2 was produced with (16)O/D 2 (16)O than with (16)O/H 2 (16)O. These differences are likely due to primary kinetic isotope effects due to the differences in O-H and O-D bond energies.     

Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid

Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric phospholipids. To combat this interaction we have investigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathy associated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show that Cu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The copper complex formed is stable in solution as assessed by mass spectrometry and 1H NMR diffusion experiments. Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) to amino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer to serum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility that copper complexes of MPA may be useful in a therapeutic situation.