Model systems for flavoenzyme activity: a tuneable intramolecularly hydrogen bonded flavin-diamidopyridine complex

We report the electrochemically tuneable intramolecular hydrogen bonding interactions between a covalently linked flavin-diamidopyridine unit.     

Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5

Background  

The cyclic AMP specific phosphodiesterase, PDE4D5 interacts with the β-propeller protein RACK1 to form a signaling scaffold complex in cells. Two-hybrid analysis of truncation and mutant constructs of the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5 were used to define a domain conferring interaction with the signaling scaffold protein, RACK1.     

Ferrocene incorporating host-guest dyads with electrochemically controlled three-pole hydrogen bonding properties

We describe the electrochemically controlled hydrogen bonding interactions between the isobutyl flavin/2,6-diferrocenylamidopyridine (2·5) and 9,10-phenanthrenequinone/1-ferrocenyl-3-hexylurea (4·6) dyads. Cyclic and square wave voltammetry studies have shown that the binding efficiencies between these moieties can be electrochemically actuated in non-polar (CH₂Cl₂ for 2·5) or polar (DMF for 4·6) organic solvents between three distinct states.     

Five-coordinate Fe(III)NO and Fe(II)CO porphyrinates: where are the electrons and why does it matter?

Recent years have seen dramatic growth in our understanding of the biological roles of nitric oxide (NO). Yet, the fundamental underpinnings of its reactivities with transition metal centers in proteins and enzymes, the stabilities of their structures, and the relationships between structure and reactivity remains, to a significant extent, elusive. This is especially true for the so-called ferric heme nitrosyls ([FeNO](6) in the Enemark-Feltham scheme). The Fe-CO and C-O bond strengths in the isoelectronic ferrous carbonyl complexes are widely recognized to be inversely correlated and sensitive to structural, environmental, and electronic factors. On the other hand, the Fe-NO and N-O bonds in [FeNO](6) heme complexes exhibit seemingly inconsistent behavior in response to varying structure and environment. This report contains resonance Raman and density functional theory results that suggest a new model for FeNO bonding in five-coordinate [FeNO](6) complexes. On the basis of resonance Raman and FTIR data, a direct correlation between the nu(Fe)(-)(NO) and nu(N)(-)(O) frequencies of [Fe(OEP)NO](ClO(4)) and [Fe(OEP)NO](ClO(4)).CHCl(3) (two crystal forms of the same complex) has been established. Density functional theory calculations show that the relationship between Fe-NO and N-O bond strengths is responsive to FeNO electron density in three molecular orbitals. The highest energy orbital of the three is sigma-antibonding with respect to the entire FeNO unit. The other two comprise a lower-energy, degenerate, or nearly degenerate pair that is pi-bonding with respect to Fe-NO and pi-antibonding with respect to N-O. The relative sensitivities of the electron density distributions in these orbitals are shown to be consistent with all published indicators of Fe-N-O bond strengths and angles, including the examples reported here.     

Decarbonylative ether dissection by iridium pincer complexes

A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported, mediated by iridium(i) complexes supported by aminophenylphosphinite (NCOP) pincer ligands. The decarbonylation, which involves the cleavage of one C–C bond, one C–O bond, and two C–H bonds, along with formation of two new C–H bonds, was serendipitously discovered upon dehydrochlorination of an iridium(iii) complex containing an aza-18-crown-6 ether macrocycle. Intramolecular cleavage of macrocyclic and acyclic ethers was also found in analogous complexes featuring aza-15-crown-5 ether or bis(2-methoxyethyl)amino groups. Intermolecular decarbonylation of cyclic and linear ethers was observed when diethylaminophenylphosphinite iridium(i) dinitrogen or norbornene complexes were employed. Mechanistic studies reveal the nature of key intermediates along a pathway involving initial iridium(i)-mediated double C–H bond activation.

A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported.     

Hydrogen bonding in redox-modulated molecular recognition. An experimental and theoretical investigation

Two receptors, a diaminotriazine derivative (DAT) and diamidopyridine (DAP), are complementary to the electroactive naphthalimide (N) through three-point hydrogen bonding. The association constants of the two receptors were evaluated for both the fully oxidized and the radical anion forms of N. In the oxidized state, the two receptors displayed identical binding constants. Diamidopyridine, however, lowers the reduction potential of naphthalimide to a far greater extent than does diaminotriazine, indicating a greater affinity for diamidopyridine by naphthalimide in the radical anion form. This behavior was mirrored by EPR experiments that showed small deviations from the hyperfine coupling pattern of N(red) in the presence of DAT, with greater effects seen for the N(red).DAP complex. Computational simulations using the UB3LYP/6-311+G(d,p)//UHF/6-31G(d) hybrid gave theoretical hyperfine constants in good quantitative agreement with the experimental results. Using this correlation, we determined that electrostatics and hydrogen bond polarizability play key roles in controlling redox-modulated molecular recognition.     

A theoretical interpretation of isotope effects in mixtures of light and heavy water—II

Solvent isotope effects for H₂O---D₂O mixtures and for ionic hydration equilibria in such mixtures can be calculated from the structure difference between D₂O and H₂O and that between HDO and H₂O and the relative amounts of the three waters. The behavior of acids in H₂O---D₂O mixtures is considered in detail. Dissociation constants of acetic acid are calculated over the complete range of deuterium concentrations and found to agree with the experimentally determined ones. The Gross equation for the dependence of isotope effect on mole fraction of deuterium for acid-catalyzed reaction of substrates S proceeding via SL⁺ transition states (L=H or D) is derived from first principles.     

Backbone modified small bite-angle diphosphines: Synthesis and molecular structures of [M(CO)4{X2PC(RR)PX2}] (M = Mo, W; X = Ph, Cy; R = H, Me, Et, Pr, allyl, R = Me, allyl)

A range of new small bite-angle diphosphine complexes, [M(CO)₄{X₂PC(R¹R²)PX₂}] (M = Mo, W; X = Ph, Cy; R¹ = H, Me, Et, Pr, allyl, R² = Me, allyl), have been prepared via elaboration of the methylene backbones in [M(CO)₄(X₂PCH₂PX₂)] as a result of successive deprotonation and alkyl halide addition. When X = Ph it proved possible to replace both methylene protons but for X = Cy only one substitution proved possible. This is likely due to the electron-releasing nature of the cyclohexyl groups but may also be due to steric constraints. Attempts to prepare the bis(allyl) substituted complex [Mo(CO)₄{Ph₂PC(allyl)₂PPh₂}] were only moderately successful. The crystal structures of nine of these complexes are presented.     

{\rtf1\ansi\ansicpg1250\deff0\deflang1038\deflangfe1038\deftab708{\fonttbl{\f0\froman\fprq2\fcharset238{\*\fname Times New Roman;}Times New Roman CE;}} \viewkind4\uc1\pard\f0\fs24 Status of software for PGNAA bulk analysis by the Monte Carlo - Library Least-Squares (MCLLS) approach \par }

Summary {\rtf1\ansi\ansicpg1250\deff0\deflang1038\deflangfe1038\deftab708{\fonttbl{\f0\froman\fprq2\fcharset238{\*\fname Times New Roman;}Times New Roman CE;}} \viewkind4\uc1\pard\f0\fs24 The Center for Engineering Applications of Radioisotopes (CEAR) has been working for about ten years on the Monte Carlo - Library Least-Squares (MCLLS) approach for treating the nonlinear inverse analysis problem for PGNAA bulk analysis. This approach consists essentially of using Monte Carlo simulation to generate the libraries of all the elements to be analyzed plus any other required libraries. These libraries are then used in the linear Library Least-Squares (LLS) approach with unknown sample spectra to analyze for all elements in the sample. The other libraries include all sources of background which includes: (1) gamma-rays emitted by the neutron source, (2) prompt gamma-rays produced in the analyzer construction materials, (3) natural gamma-rays from K-40 and the uranium and thorium decay chains, and (4) prompt and decay gamma-rays produced in the NaI detector by neutron activation. A number of unforeseen problems have arisen in pursuing this approach including: (1) the neutron activation of the most common detector (NaI) used in bulk analysis PGNAA systems, (2) the nonlinearity of this detector, and (3) difficulties in obtaining detector response functions for this (and other) detectors. These problems have been addressed by CEAR recently and have either been solved or are almost solved at the present time. We have now finished the development of Monte Carlo simulation for all of the libraries except the prompt gamma-ray library from the activation of the NaI detector. We must first determine a treatment for the coincidence schemes for Na and particularly I to complete the Monte Carlo simulation of this last library. \par }