Tetrahedral State Research Articles

NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: changes in the (1)H, (13)C and (15)N NMR chemical shifts of turkey ovomucoid third domain upon binding to bovine chymotrypsin A(alpha).

The substrate-like inhibition of serine proteinases by avian ovomucoid domains has provided an excellent model for protein inhibitor-proteinase interactions of the standard type. 1H,15N and 13C NMR studies have been undertaken on complexes formed between turkey ovomucoid third domain (OMTKY3)2 and chymotrypsin A(alpha) (Ctr) in order to characterize structural changes occurring in the Ctr binding site of OMTKY3. 15N and 13C were incorporated uniformly into OMTKY3, allowing backbone resonances to be assigned for OMTKY3 in both its free and complex states. Chemical shift perturbation mapping indicates that the two regions, K13-P22 and N33-A40, are the primary sites in OMTKY3 involved in Ctr binding, in full agreement with the 12 consensus proteinase-contact residues of OMTKY3 defined previously on the basis of X-ray crystallographic and mutational analysis. Smaller chemical shift perturbations in selected other regions may result from minor structural changes on binding. Through-bond 15N-13C correlations between P1-13C' and P1'-15N in two-dimensional H(N)CO and HN(CO) NMR spectra of selectively labeled OMTKY3 complexed with Ctr indicate that the scissile peptide bond between L18 and E19 of the inhibitor is intact in the complex. The chemical shifts of the reactive site peptide bond indicate that it is predominantly trigonal, although the data are not inconsistent with a slight perturbation of the hybridization of the peptide bond toward the first tetrahedral state along the reaction coordinate.

Mesoporous titanium phosphate molecular sieves with ion-exchange capacity.

Novel open framework molecular sieves, titanium(IV) phosphates named, i.e., TCM-7 and -8 (Toyota Composite Materials, numbers 7 and 8), with new mesoporous cationic framework topologies obtained by using both cationic and anionic surfactants are reported. The (31)P MAS NMR, UV-visible absorption, and XANES data suggest the tetrahedral state of P and Ti, and stabilization of the tetrahedral state of Ti in TCM-7/8 is due to the incorporation of phosphorus (at Ti/P = 1:1) vis-à-vis the most stable octahedral state of Ti in the pure mesoporous TiO(2). Mesoporous TCM-7 and -8 show anion exchange capacity due to the framework phosphonium cation and cation exchange capacity due to defective P-OH groups. The high catalytic activity in the liquid-phase partial oxidation of cyclohexene with a dilute H(2)O(2) oxidant supports the tetrahedral coordination of Ti in these materials.

Synthesis of tris(Cyclohexylisocyanide)bis(Triphenylphosphine)Cobalt(II) Perchlorate. An Example of Unusual Stabilization of the Cobalt(II) Oxidation State.

A cobalt(II) complex with alkylisocyanide and triarylphosphine ligands is reported. Tris(cyclohexylisocyanide)bis(triphenylphosphine)cobalt(II) perchlorate, [Co(CNC6H11)3(PPh3)2](ClO4)2, was synthesized by PPh3 ligand-substitution in [Co(CNC6H11)4(AsPh3)2](ClO4)2 in which the distribution of product among [Co(CNC6H11)3(PPh3)2](ClO4)2, [Co(CNC6H11)3(PPh3)2](ClO4, [Co(OPPh3)4](ClO4)2, and unreacted [Co(CNC6H11)4(AsPh3)2](ClO4)2 was controlled in part by the concentration of PPh3 and reaction time. [Co(CNC6H11)3(PPh3)2](ClO4)2 was also synthesized by AgClO4 oxidation of [Co(CNC6H11)3(PPh3)2]ClO4. [Co(CNC6H11)3(PPh3)2](ClO4)2 is easily reduced to [Co(CNC6H11)3(PPh3)2]ClO4 with N2H4.H2O and decomposes into [Co(OPPh3)4](ClO4)2 on prolonged dissolution in CH2Cl2 solution, especially under UV (365 nm) irradiation. Physical properties for [Co(CNC6H11)3(PPh3)2](ClO4)2 and [Co(OPPh3)4](ClO4)2 support trigonal bipyramidal and tetrahedral solution and solid state stereochemistries, respectively, but both complexes have limited stability in most solvents. Referee I: T. Burkey Referee II: K. M. DeArmond

The 3ν1 + ν3 vibrational overtone spectrum of 13CH4

Abstract The 3 ν 1 + ν 3 vibrational overtone spectrum of 13 CH 4 is recorded under Doppler-limited resolution conditions using a titanium sapphire laser-based photoacoustic spectrometer. Data at two temperatures, 100 and 293 K, are presented. The observed spectral congestion is qualitatively similar to that observed for 12 CH 4 , but the detailed ro-vibrational structure of the two isotope variants is completely different. The data reflect the complicating influences of tetrahedral fine structure and vibrational state mixing.

A phosphinic acid dipeptide analogue to stabilize peptide drugs during their intranasal absorption.

A major challenge in intranasal delivery of peptides is to overcome the enzymatic barrier that limits their absorption. Aminopeptidase inhibitors may be useful for improving systemic delivery of peptide drugs administered nasally. A phosphinic acid dipeptide analogue, a transition-state analogue aminopeptidase inhibitor in which the phosphinate moiety exists in a tetrahedral state mimicking peptides during their enzymatic hydrolysis, was synthesized and tested nasally in situ in rats. This inhibitor was found to inhibit greatly the degradation of the model peptide leucine-enkephalin in the nasal perfusate at less than or equal to 2 microM concentrations. The nasal peptidase hydrolytic activity was reversible after exposure to the inhibitor. This inhibitor has the advantage of efficacy at very low concentrations and reversibility of effects.

Structure and magnetic susceptibility of irradiated sodium borate glasses containing nickel oxide

The effect of introducing soda to boric oxide on the optical absorption infrared spectra and magnetic susceptibility of sodium borate glass system containing nickel oxide was studied. It was found that increasing of Na2O helps in forming the BO4 group and nonbridging oxygen and the nickel ions change from the octahedral state to the tetrahedral state. The magnetic susceptibility also increases rapidly with gradual increase of soda content up to 20 mol%, and then slightly increases, this may be due to the change in the coordination number of nickel ions. Also the effect of the addition of nickel oxide was studied, it was found that the values of magnetic susceptibility increases with the gradual increase of the nickel oxide, which is due to the increase of Ni2+ in octahedral coordination.

The hybridization state of nitrogen as a conformational variable in biologically active molecules

A survey of the conformations found in the crystal structures of central nervous system-active drugs and related nitrogen-containing structures shows that there is a continuous distribution of conformations from that typical of the sp3(N-torsion 120°) to that typical of the sp2(N-torsion 180°) hybridization state. In general the presence of an adjacent carbonyl group favours a planar geometry, while the lack of any conjugating group favours the tetrahedral state, but nitrogens with aromatic substituents cover the entire range between the two states. Other than those cases where the nitrogen has aromatic substituents or is in a sterically constrained ring-system (e.g., cage compounds), steric effects have relatively little influence on the conformation at nitrogen. In these cases calculations using various techniques suggest that simple non-bonded potential calculations may be the most practical approach to the evaluation of nitrogen geometry. Even in small molecules, however, calculated barriers to nitrogen inversion are generally low and poorly reproduced by either molecular orbital or classical calculations.

Role of catalytic residues in the formation of a tetrahedral adduct in the acylation reaction of bovine β-trypsin: A molecular orbital study

In the acylation reaction of serine proteases the effect of amino acid residues on the geometrical change of the catalytic site from Michaelis to tetrahedral state was studied by using ab initio molecular orbital calculations. Amino acid residues in the catalytic site and the peptide substrate were calculated as a quantum mechanical region, and all the other amino acid residues and the calcium ion were included in the calculation as the electrostatic effects. The effects of Asp102, Asp194, N-terminus and the oxyanion binding site are large. The oxyanion binding site directly stabilizes the tetrahedral substrate. Asp102 stabilizes the enzyme intermediate, interacting with the protonated His57 residue. In order to elucidate the roles of Asp102 and the oxyanion binding site, energy decomposition analyses were done for the intermolecular interactions. The contribution of Asp102 and the oxyanion binding site to the decrease of energy in the geometrical change is due to the electrostatic effect. The energies of the proton shuttle from Ser195 O γ to the leaving group of the substrate were calculated for amide and ester substrate models.

Pseudopotential, MC-SCF and limited CI calculations on nickel-bis-dithiolene

The pseudopotential method is used to perform multiconfigurational (MC) SCF and full valence configuration interaction (CI) calculations on the dianion of nickel-bis-dithiolene, [Ni(S 2C 2H 2) 2] 2−. Both a planar (D 2h) and a near tetrahedral (D 2d) conformation are considered. Charge distributions are calculated, yielding a charge on Ni of 0.22 in the planar and 0.57 in the tetrahedral case. The experimental ground state, the planar 1Ag state, approaches a 3d 9 configuration on Ni (the d-population equals 8.87), while the nickel 3d-population of all other calculated states ranges from 8.35 to 8.69. The single d—d excitation spectrum for the planar complex is discussed, and the first transition is computed to be 1Ag → 1B 1g. Intramolecular rotation, i.e., one ligand ring rotating with respect to the other, is also discussed. The rotation is proposed to occur via a tetrahedral triplet intermediate since the relevant singlet tetrahedral state is estimated to lie more than 1 eV higher than the triplet intermediate. The discussion of the intramolecular rotation is made difficult by an error in the calculated singlet—triplet splittings. Possible causes of this error are pointed out.

Phenylboronic acid as a ligand for biospecific chromatography of serine proteinases

Via attachment of a-(ω-aminoethyl)phenylboronic acid to CH-Sepharose in the presence of water-soluble carbodiimide, a new sorbent for the biospecific chromatography of serine proteinases was obtained. The sorbent was shown to be suitable for the purificatio of subtilism, a-chymotrypsin and trypsin. It is assumed that the serine hydroxyl group at the active of the enzyme forms, with the boronic acid moiety of the ligand, a structure that imitates transition enzyme-substrate complex. The presence of glycerol selectively improves the binding of serine proteinases. presumably because of stabilization of the tetrahedral state of the boron atom. Direct isolation of subtilisn from a Bacillus subtilis cultural filtrate on phenylboronic acid-containing sorbent gives a virtually homogeneous enzyme (42-fold purification) in a nearly-quantitative yield.