Entatic Research Articles

Molecular modelling of carboranes using distance restraints: the molecular dynamics simulation of appended thioether macrocycles

A molecular mechanics model for o-carborane cages has been developed, using distance restraints to hold the polyhedron in position. The combination of o-carborane cage interatomic distance restraints (a modified central force field) and CHARMm parameters gives a good representation of the carborane cage geometry. Molecular dynamic simulations of macrocyclic thioethers ligated to the carbons of the carborane have been carried out. The rigid cage section seems to provide an accessible interconversion route between conformers of the macrocycle, effectively an entatic state. The new carborane 1,2-(6′-oxa-3′,9′-dithiaundecane-1′,11′-diyl)-1,2-dicarba-closo-dodecborane, the four-step synthesis and crystal structure of which are presented, provided a contrasting macrocyclic appendage with thioethers indirectly linked to the o-carborane cage through ethane bridges. Molecular dynamics simulation of this molecule was also carried out.

ChemInform Abstract: Crystal and Molecular Structure of (5,5,8,8,13,13,16,16‐Octamethyl‐1,4,9,12‐tetraazacyclohexadeca‐1,3,9,11‐tetraene)copper(I) Perchlorate. A Model for the Entatic State in Blue Copper Proteins

ChemInformVolume 19, Issue 33 Organoelement Compounds ChemInform Abstract: Crystal and Molecular Structure of (5,5,8,8,13,13,16,16-Octamethyl-1,4,9,12-tetraazacyclohexadeca-1,3,9,11-tetraene)copper(I) Perchlorate. A Model for the Entatic State in Blue Copper Proteins J. H. TIMMONS, J. H. TIMMONS Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorJ. W. L. MARTIN, J. W. L. MARTIN Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorA. E. MARTELL, A. E. MARTELL Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorP. R. RUDOLF, P. R. RUDOLF Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorA. CLEARFIELD, A. CLEARFIELD Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this author J. H. TIMMONS, J. H. TIMMONS Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorJ. W. L. MARTIN, J. W. L. MARTIN Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorA. E. MARTELL, A. E. MARTELL Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorP. R. RUDOLF, P. R. RUDOLF Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this authorA. CLEARFIELD, A. CLEARFIELD Dep. Chem., Tex. A&M Univ., College Station, TX 77843, USASearch for more papers by this author First published: August 16, 1988 https://doi.org/10.1002/chin.198833279Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume19, Issue33August 16, 1988 RelatedInformation

Crystal and molecular structure of (5,5,8,8,13,13,16,16-octamethyl-1,4,9,12-tetraazacyclohexadeca-1,3,9,11-(tetraene)copper(I) perchlorate. A model for the entatic state in blue copper proteins

Crystal and molecular structure of (5,5,8,8,13,13,16,16-octamethyl-1,4,9,12-tetraazacyclohexadeca-1,3,9,11-(tetraene)copper(I) perchlorate. A model for the entatic state in blue copper proteins

Metallo-enzyme catalysis: the entatic state

Metallo-enzyme catalysis: the entatic state

Metallo-enzyme catalysis: the entatic state

The best of all possible homogeneous catalysts must have carefully designed coordination spheres such that their acid/base or redox ground state properties are correctly tuned for the optimum expression of function, and such that the sites retain sufficient mobility to allow the catalyst atoms to pass easily along the reaction coordinates. Biological evolution has had the opportunity to generate such catalysts through the use of advantageous mutations. The coordination sphere in metallo-enzymes is controlled by the local amino acid composition, the fold energy of the protein and the use of a variety of synthesised special ligands. The question arises as to how near to perfection have the metallo-protein catalysts become. Specially and specifically strained coordination centres of many metallo-enzymes in their ground states have already been identified and called ‘entatic’. We shall show that biological evolution has done a remarkable series of special syntheses, and that indeed the resultant coordination compounds can be described as very well designed for catalytic purposes, with respect to both structure and mobility. They may fall just short of perfection in that metallo-proteins are not simple catalysts but must perform one or two other functions.

ChemInform Abstract: ALUMINUM‐27 NMR, A QUADRUPOLAR PROBE FOR THE ENTATIC STATE AND STABILITY OF METALLOCHROMOPHORES. A STUDY OF FERRICHROME PEPTIDES AT 65.1 MHZ

Chemischer InformationsdienstVolume 11, Issue 28 Physical Organic Chemistry ChemInform Abstract: ALUMINUM-27 NMR, A QUADRUPOLAR PROBE FOR THE ENTATIC STATE AND STABILITY OF METALLOCHROMOPHORES. A STUDY OF FERRICHROME PEPTIDES AT 65.1 MHZ M. LLINAS, Search for more papers by this authorA. DE MARCO, Search for more papers by this author M. LLINAS, Search for more papers by this authorA. DE MARCO, Search for more papers by this author First published: July 15, 1980 https://doi.org/10.1002/chin.198028054Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume11, Issue28July 15, 1980 RelatedInformation

Aluminum-27 NMR, a quadrupolar probe for the entatic state and stability of metallochromophores. A study of ferrichrome peptides at 65.1 MHz

Aluminum-27 NMR, a quadrupolar probe for the entatic state and stability of metallochromophores. A study of ferrichrome peptides at 65.1 MHz

SYNTHETIC ANALOGS OF THE ACTIVE SITES OF OXIDIZED AND REDUCED RUBREDOXIN

The bischelate monoanion (Fe((SCH2)2C6H4)2)1_ contains an unconstrained, near-tetrahedral Fe(III)-S4 coordination unit (similar to the Fe-SU coordination unit occurring in rubredoxin proteins) and exhibits the Fe(III)/Fe(II) redox couple. Mossbauer parameters at 77 K are isomer shift S = 0.13 mm/s (relative to iron metal) and electric quadrupole splitting AZIQ = 0.57 mm/s. Application of an external magnetic field parallel to the direction of observa­ tion at 4.2 K induces a saturation magnetic hyperfine field of — 380 kOe. Upon reduction to the dianion (Fe((SCH2)2C6H.t)2)2- the isomer shift changes to S = 0.61 mm/s and the quadrupole splitting at 4.2 K to A£Q = 3.34 mm/s. From the temperature dependence of AEQ for 1.4 K < T < 295 K we infer the splitting of the ground orbital doublet, e(dz2, dX2-yi), to be A s 900 cm-1. External magnetic fields up to 80 kOe reveal the sign of Vzz to be negative indicating that the ground orbital has dz% symmetry and induce a magnetic hyperfine interaction of negative sign. For H0 = 60 kOe, Hm = — 128 kOe. |HM | increases with increasing H0, showing that saturation has not been reached up to Ho = 80 kOe, and implying a zero field splitting of several cm -1 of the electronic ground state. These results as well as magnetic moment measurements for the unconstrained model compounds are comparable to measurements in oxidized and reduced rubredoxin and imply that an « entatic state » description of rubredoxin is not valid.

Charge pair model of bioenergetics: redox enzymes.

A model of electron transfer between redox enzymes is constructed on the assumption that the apoenzyme contains orientable units, which are tentatively identified with flipping amino acids. The model is based on the entatic state hypothesis, and the rate of electron transfer is derived.

Synthetic analogs of active sites of iron-sulfur proteins: bis (o-xylyldithiolato) ferrate (III) monoanion, a structurally unconstrained model for the rubredoxin Fe-S4 unit.

To complete the set of synthetic analogs of the three recognized types of active sites in iron-sulfur redox proteins, the compound (Et4N)[Fe((SCH2)2C6H4)2], derived from o-xylyl-alpha,alpha'-dithiol, has been prepared and its structure has been determined by x-ray diffraction. The bischelate anion contains a near-tetrahedral Fe(III)-S4 coordination unit with small rhombic distortions and all Fe-S bond distances in the range 2.252-2.279 A. Its electronic properties have been partially characterized by measurement of electronic absorption, paramagnetic resonance, Mössbauer spectra, and magnetic susceptibility. The analog, as the protein, exhibits the Fe(III)/Fe(II) redox couple. These results substantiate designation of [Fe((SCH2)2C6H4)2]- as a synthetic analog of the Fe(III)(S-Cys)4 center in oxidized rubredoxin proteins. Comparison of the analog structure with that of the Clostridium pasteurianum rubredoxin active site shows that the former is substantially less distorted from idealized tetrahedral symmetry, and is considered to represent an essentially unconstrained structural model of the latter. Provided the grossly distorted tetrahedral stereochemistry of the protein site persists through final structural refinement, the analog-protein structural comparison supports an entatic state description of oxidized rubredoxin.

Collective aspects of conformons and the electron transfer chain

A set of interacting harmonic oscillators is used as a model to define a low frequency collective mode in protein molecules. Such a mode may arise from electron-phonon interactions in second order perturbation theory. The mathematical scheme is analogous to those used in the theory of carcadian rhythms and in the theory of superconductivity. This collective mode may receive energy from electrons in the electron transfer chain (conformon) and pass the energy on to other similar modes. The low frequency of the mode leads to slow reactions, in agreement with experimental data. The model is compatible with some general characteristics of the electron transfer chain and its constituents: high thermodynamic efficiency, redox pools, redox switches, entatic states and conformational free energy transfer.

Thermal, magnetic and mossbauer studies on ferric porphyrin hemichromes

A current area of bioinorganic interest concerns the behavior of ferric porphyrins in solution with nitrogenous bases. PMR studies have given evidence for (1) low spin ( S = 1 2 ) = high spin ( S = 5 2 or 2 3 ) equilibria in certain systems [1, 2], and (2) five coordinate ( S = 5 2 monoimidazole ferric porphyrins in equilibrium with low spin bisimidazole forms [3] in solution. In contrast, spectrophotometric titrations of Cl-Fe(III)tetraphenylporphin with imidazole in acetone [4] and methylene chloride [5] solvents show an equilibria between only Cl-Fe(III)TPP and ▪ TPP, Cl −, with no monoimidazole adducts present. We have begun a program of using thermal means to generate “unusual” metal ion geometries of metalloporphyrins in the solid state as models of the metalloenzymes “entatic state” [6]. We report magnetic, thermal and Mossbauer data on a variety of solid hemichromes, which show certain parallel features with the behavior of hemichromes in solution. In particular, we have synthesized by thermal means high spin monoimidazole Fe(III) porphyrin complexes.

The spectrum of cobalt bovine procarboxypeptidase A, an index of catalytic function.

The spectra of functionally essential, chromophoric metal atoms of metalloenzymes are thought to reflect catalytic potential [Vallee and Williams (1968) Proc. Nat. Acad. Sci. USA 59, 498]. The spectra of cobalt procarboxypeptidase and their perturbations by substrates and inhibitors are virtually the same as those of cobalt carboxypeptidase; both are consistent with a distorted tetrahedral geometry about the cobalt atom, suggesting irregular coordination geometries and low symmetries of metal-binding sites. We have, therefore, examined the enzymatic properties of cobalt procarboxypeptidase and found that it catalyzes the hydrolysis of a series of haloacylated amino acids at rates equal to or greater than those of native zinc carboxypeptidase. These observations demonstrate the existence both of the catalytic and of the binding sites for haloacylated amino acids of the zymogen, even before activation. Hence, the magnitude of conformational changes at the catalytic site thought to accompany its activation must be very small, no matter what their magnitude might be elsewhere in the molecule. The data support the entatic state hypothesis and suggest that it may profitably guide the exploration of catalytic potential of metalloproteins and metal-protein complexes.

The entatic state.

Vallee and Williams (1968) defined the entatic state as an abnormal condition of a region of a protein which had arisen through the internal activation of this region by geometric and/or electronic strain. This strain was considered to be due to the conformational demands which gave stability to other parts of the protein, the whole being at a minimum free energy. A diagram illustrating the rate enhancement gained by the activation of the special region of the protein is shown in Fig. 1, which is to be contrasted with the conventional diagram for enzyme catalysis, Fig. 2. It may be clearer to state that the entatic region of the enzyme has suffered a unimolecular activation of its groups relative to the state of these groups in a randon-coiled protein. The customary analysis (Fig. 2) refers to a stabilization of the transition state of a bimolecular complex. In many respects, then,...