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Biomedical subjects

Gerald H Lushington

Publications and source records attributed to Gerald H Lushington.

At least 19 recordsLinked to original sources
PubMed2006

Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues.

The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol.

Adenosine Triphosphate↗
PubMed2006

The 2,6-diisocyanoazulene motif: synthesis and efficient mono- and heterobimetallic complexation with controlled orientation of the azulenic dipole.

Synthesis of the remarkably air- and thermally stable 2,6-diisocyano-1,3-diethoxycarbonylazulene linker from 2-amino-1,3-diethoxycarbonylazulene in 57% cumulative yield was developed. Incorporation of the ester "arms" in the design of this first diisocyanoazulene bridge permitted fully controlled stepwise installation and complexation of its isocyano junction groups. The -CO(2)Et arms in 2,6-diformamido-1,3-diethoxycarbonylazulene effectively suppress the rate of dehydration of its 2-NHCHO end relative to that of the 6-NHCHO end leading to practically exclusive formation of 6-isocyano-2-formamido-1,3-diethoxycarbonylazulene upon treatment of the above diformamide with an equimolar amount of POCl(3). This crystallographically characterized 6-isocyano-2-formamidoazulene derivative was employed to access mono- and heterobimetallic complexes of the 2,6-diisocyanoazulene scaffold with controlled orientation of the azulenic dipole. A complete series of monometallic, homobimetallic, and isomeric heterobimetallic ([M] = M(CO)(5), M = Cr and/or W) complexes of the 2,6-diisocyanoazulene motif was isolated and studied by a variety of techniques, including X-ray crystallography. The metal-to-bridge charge transfer in mono- and dinuclear adducts of 2,6-diisocyanoazulene, the assignment of which was corroborated by time-dependent density functional theory calculations, occurs at a dramatically lower energy as compared to the analogous systems featuring the 1,4-diisocyanobenzene scaffold. Moreover, the metal-to-diisocyanide charge transfer exhibits a substantially greater red shift upon binucleation of the mononuclear [M(CO)(5)] adducts of the nonbenzenoid 2,6-diisocyanoazulene linker versus the 1,4-diisocyanobenzene bridge.

Journal Article↗
PubMed2006

Support vector machines in HTS data mining: Type I MetAPs inhibition study.

This article reports a successful application of support vector machines (SVMs) in mining high-throughput screening (HTS) data of a type I methionine aminopeptidases (MetAPs) inhibition study. A library with 43,736 small organic molecules was used in the study, and 1355 compounds in the library with 40% or higher inhibition activity were considered as active. The data set was randomly split into a training set and a test set (3:1 ratio). The authors were able to rank compounds in the test set using their decision values predicted by SVM models that were built on the training set. They defined a novel score PT50, the percentage of the test set needed to be screened to recover 50% of the actives, to measure the performance of the models. With carefully selected parameters, SVM models increased the hit rates significantly, and 50% of the active compounds could be recovered by screening just 7% of the test set. The authors found that the size of the training set played a significant role in the performance of the models. A training set with 10,000 member compounds is likely the minimum size required to build a model with reasonable predictive power.

Algorithms↗
PubMed2006

Mechanistic insight into acetylcholinesterase inhibition and acute toxicity of organophosphorus compounds: a molecular modeling study.

Acute toxicity of organophosphorus (OP) compounds results mainly from irreversible acetylcholinesterase (AChE) inhibition; however OP toxicity frequently hinges on prior biotransformations that produce toxic metabolites. To account for both precursor metabolic effects and primary AChE inhibition, we included absorption, distribution, metabolism, excretion (ADME) effects, ligand binding, and reactive AChE phosphorylation and aging in a detailed but computationally expedient phenomenological toxicity model. Ligand negative accessible surface area (NASA) was used as a generic ADME descriptor, while relevant metabolic, phosphorylation, and aging reactions were assessed via quantum chemical enthalpy calculations, and the binding affinity of the Michaelis complex was quantified via Comparative Molecular Field Analysis (CoMFA). The resulting model correlates very well (R2 = 0.90) with experimental acute toxicity measurements and provides useful mechanistic insight into the underlying toxicity. Model predictivity was validated by leave-one-out cross-validation (Q2 = 0.82). The Michaelis binding affinity descriptor has the largest weight in our model, but subsequent covalent inhibition and prior ADME effects also exhibit significant effects.

Absorption↗
PubMed2006

Anti-endotoxin agents. 3. Rapid identification of high-affinity lipopolysaccharide-binding compounds in a substituted polyamine library.

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of the outer leaflet of the outer-membrane of Gram-negative bacteria. Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient, worldwide. The sequestration of circulatory endotoxin may be a viable therapeutic strategy for the prophylaxis and treatment of Gram-negative sepsis. We have earlier shown that the pharmacophore necessary for small molecules to bind LPS involves two protonatable cationic functions separated by about 15 A, permitting the simultaneous interaction with the negatively charged phosphates on lipid A, the toxically active center of endotoxin. In this report, screening of a multi-thousand membered polyamine library through the combined use of computational and bioassay-guided screens resulted in the discovery of two novel classes of LPS-binding agents. These are represented by the 1) spermine sulfonamides and 2) C-aryl-substituted spermine analogs. We present the selection approach, screening results, computational multivariate analyses and initial structure-activity relationship evaluation herein.

Antitoxins↗
PubMed2006

Acetylcholinesterase: molecular modeling with the whole toolkit.

Molecular modeling efforts aimed at probing the structure, function and inhibition of the acetylcholinesterase enzyme have abounded in the last decade, largely because of the system's importance to medical conditions such as myasthenia gravis, Alzheimer's disease and Parkinson's disease, and well as its famous toxicological susceptibility to nerve agents. The complexity inherent in such a system with multiple complementary binding sites, critical dynamic effects and intricate mechanisms for enzymatic function and covalent inhibition, has led to an impressively diverse selection of simulation techniques being applied to the system, including quantum chemical mechanistic studies, molecular docking prediction of noncovalent complexes and their associated binding free energies, molecular dynamics conformational analysis and transport kinetics prediction, and quantitative structure activity relationship modeling to tie salient details together into a coherent predictive tool. Effective drug and prophylaxis design strategies for a complex target like this requires some understanding and appreciation for all of the above methods, thus it makes an excellent case study for multi-tiered pharmaceutical modeling. This paper reviews a sample of the more important studies on acetylcholinesterase and helps to elucidate their interdependencies. Potential future directions are introduced based on the special methodological needs of the acetylcholinesterase system and on emerging trends in molecular modeling.

Acetylcholinesterase↗
PubMed2005

Discover protein sequence signatures from protein-protein interaction data.

BACKGROUND: The development of high-throughput technologies such as yeast two-hybrid systems and mass spectrometry technologies has made it possible to generate large protein-protein interaction (PPI) datasets. Mining these datasets for underlying biological knowledge has, however, remained a challenge. RESULTS: A total of 3108 sequence signatures were found, each of which was shared by a set of guest proteins interacting with one of 944 host proteins in Saccharomyces cerevisiae genome. Approximately 94% of these sequence signatures matched entries in InterPro member databases. We identified 84 distinct sequence signatures from the remaining 172 unknown signatures. The signature sharing information was then applied in predicting sub-cellular localization of yeast proteins and the novel signatures were used in identifying possible interacting sites. CONCLUSION: We reported a method of PPI data mining that facilitated the discovery of novel sequence signatures using a large PPI dataset from S. cerevisiae genome as input. The fact that 94% of discovered signatures were known validated the ability of the approach to identify large numbers of signatures from PPI data. The significance of these discovered signatures was demonstrated by their application in predicting sub-cellular localizations and identifying potential interaction binding sites of yeast proteins.

Binding Sites↗
PubMed2005

Interactions of organophosphorus and related compounds with cholinesterases, a theoretical study.

Acetylcholinesterase (AChE) is an interesting research target not only because of its high enzyme catalytic rate but also because of the wide range of health effects resulting from its inhibition. This paper discusses results of a theoretical study of acetylcholinesterase inhibition using several simulation techniques. In the first technique, a novel method was developed and used for predicting the binding affinity of human AChE (huAChE) inhibitors. Results are also presented for classical molecular dynamics and quantum mechanical simulations. Theoretical proton NMR shift results are obtained and compared to experiment, and the importance of the Glu199 residue is discussed in the context of the model.

Binding Sites↗
PubMed2005

Differential interactions of G-proteins and adenylyl cyclase with nucleoside 5'-triphosphates, nucleoside 5'-[gamma-thio]triphosphates and nucleoside 5'-[beta,gamma-imido]triphosphates.

The regulatory G-proteins of adenylyl cyclase (AC), G(i) and G(s), are not only activated by GTP and the stable GTP analogs, guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) and guanosine 5'-[beta,gamma-imido]triphosphate (GppNHp), but also by hypoxanthine, xanthine, uracil and cytidine nucleotides. The latter nucleotides were previously used to analyze distinct active G-protein states. Surprisingly, recent studies have shown that inosine 5'-[gamma-thio]triphosphate and uridine 5'-[gamma-thio]triphosphate can also inhibit AC directly. Therefore, we systematically compared the interactions of nucleoside 5'-triphosphates (NTPs), nucleoside 5'-[gamma-thio]triphosphates (NTPgammaSs) and nucleoside 5'-[beta,gamma-imido]triphosphates (NppNHps) with G(i), G(s) and AC. NTPgammaSs exhibited up to 26,000-fold higher affinity for G-proteins than NTPs and NppNHps. NTPgammaSs were up to 150-fold more potent direct AC inhibitors than NTPs and NppNHps. G-proteins exhibited striking preference for guanine nucleotides compared to other purine and pyrimidine nucleotides, whereas base-selectivity of various ACs, particularly the purified catalytic subunits C1.C2, was rather poor. GTP, GTPgammaS and GppNHp exhibited much higher selectivity for G-proteins relative to AC than all other purine and pyrimidine nucleotides. We have energetically characterized the interactions of purine and pyrimidine nucleotides with AC in silico, constructing pharmacophore models that correlate well with experimental affinities and have elucidated specific amino acid residues with greatest influence on nucleotide binding. Collectively, both G-proteins and ACs bind purine and pyrimidine nucleotides, with G-proteins showing much higher base-selectivity than AC. Thus, direct inhibitory effects of nucleotides on AC should be understood and considered when probing distinct active G-protein states with non-guanine nucleotides.

Adenylyl Cyclases↗
PubMed2005

Molecular modeling analysis of the interaction of novel bis-cationic ligands with the lipid A moiety of lipopolysaccharide.

Lipopolysaccharides (LPS), otherwise termed "endotoxins", are outer-membrane constituents of Gram-negative bacteria and play a key role in the pathogenesis of "septic shock", a major cause of mortality in the critically ill patient. We have shown that the pharmacophore necessary for optimal recognition and neutralization of LPS by small molecules requires an interaction between two protonatable positive charges separated by a distance of approximately 14A, which corresponds to the distance between two anionic phosphates on the glycolipid component of LPS called lipid A. The in silico binding of a diverse set of compounds with bis-amino, -amidino, -guanidino, and -aminoguanidino functionalities, identified as potential lead scaffolds in a high-throughput screen, with lipid A was explored using molecular docking simulations. A weighted expression for binding affinity was trained relative to experimental ED(50) measurements, attaining a correlation of R(2)=0.66. Our docking results showed that the electrostatic interaction between ligands and lipid A phosphates dominates the expression and varies little across the series, and other ligand-receptor interactions seem to play a secondary role in governing the observed variations in the relative ligand binding affinity. Further, it appears that the ligand internal energy plays the primary role in differentiating between compound binding affinities which also correlated well with experimental ED(50) data (R=0.77). Application of this strategy would be useful in the de novo design of highly active endotoxin-sequestering agents.

Amidines↗
PubMed2005

Theoretically predicted structures of plasma membrane Ca(2+)-ATPase and their susceptibilities to oxidation.

Oxidative damage to the plasma membrane Ca(2+)-ATPase (PMCA) appears to contribute to the decreased clearance of intracellular Ca(2+) in the neurons of aged brain, possibly contributing to its vulnerability to numerous age-related diseases such as Alzheimer's disease. The precise sites of oxidative susceptibility have not been identified. However, it is known that calmodulin (CaM) protects the purified PMCA against oxidative inactivation, perhaps via conformational restructuring of the protein through dissociation of a 20 residue domain (C20W) in the C-terminal region that function as a CaM-binding site. In order to postulate likely oxidation sites and the mechanism underlying the protection offered by CaM, we have generated a three-dimensional model of PMCA via a combination of homology/comparative modeling, threading, protein-protein docking, and guidance from prior biochemical and analytical studies. The resulting model was validated based on surface polarity/hydrophobicity profiling, standard ProCheck, WhatIF, and PROVE checks, as well as comparison with empirical structure-function observations. This model was then used to identify likely oxidation sites by comparing time-averaged solvent accessibility of potentially oxidizable surface residues as measured from molecular dynamics simulations of intact PMCA and the PMCA sequence from which C20W has been deleted. The resulting model complex has permitted us to identify three amino acids whose solvent accessibility is greatly reduced by the C20W dissociation: Tyr 589, Met 622, and Met 831.

Adenosine Triphosphate↗
PubMed2005

Interaction of phosphonate analogues of the tetrahedral reaction intermediate with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail.

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the penultimate step of the shikimate pathway and is the target of the broad-spectrum herbicide glyphosate. Since the functionality of the shikimate pathway is vital not only for plants but also for microorganisms, EPSPS is considered a prospective target for the development of novel antibiotics. We have kinetically analyzed and determined the crystal structures of Escherichia coli EPSPS inhibited by (R)- and (S)-configured phosphonate analogues of the tetrahedral reaction intermediate. Both diastereomers are competitive inhibitors with respect to the substrates of the EPSPS reaction, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). Remarkably, the (S)-phosphonate (K(iS3P) = 750 nM), whose configuration corresponds to that of the genuine tetrahedral intermediate, is a much weaker inhibitor than the (R)-phosphonate analogue (K(iS3P) = 16 nM). The crystal structures of EPSPS liganded with the (S)- and (R)-phosphonates, at 1.5 and 1.9 A resolution, respectively, revealed that binding of the (R)-phosphonate induces conformational changes of the strictly conserved residues Arg124 and Glu341 within the active site. This appears to give rise to substantial structural alterations in the amino-terminal globular domain of the enzyme. By contrast, binding of the (S)-phosphonate renders the enzyme structure unchanged. Thus, EPSPS may facilitate the tight binding of structurally diverse ligands through conformational flexibility. Molecular docking calculations did not explain why the (R)-phosphonate is the better inhibitor. Therefore, we propose that the structural events during the open-closed transition of EPSPS are altered as a result of inhibitor action.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed2005

Deamidation of model beta-turn cyclic peptides in the solid state.

To investigate the importance of secondary structure on peptide deamidation in the solid state, two cyclic beta-turn peptides and their linear analogs were used as models of Asn residues in structured and unstructured domains, and incorporated into poly(vinyl pyrrolidone) (PVP)-based lyophilized solids. The secondary structure of the model peptides was determined in solution and the solid state using a combination of nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopy. The model beta-turn cyclic peptides were found to be type II beta-turns while the linear analogs were determined to be predominantly unstructured. Quantitatively, the cyclic peptides consisted of approximately 80% beta-turn while the linear analogs contained only 30%-35% beta-turn. To characterize the solid environment, T(g), and moisture content of the solid-state formulations were determined. Accelerated stability studies were conducted in the solid state at 37 degrees C using formulations lyophilized from solutions at pH 8.8 (0.1 M borate buffer). The effect of matrix mobility on solid-state deamidation was investigated by altering the moisture content through variation of relative humidity or the addition of a plasticizer. Cyclic peptides degraded 1.2-8 times slower than the linear analogs under all of the conditions studied. The observed rate constants, however, for all of the peptides decreased dramatically (four orders of magnitude) in the glassy solids. This suggests the greater importance of matrix mobility in solid-state degradation. Molecular dynamics (MD) simulations were also performed to explore the low energy, preferred state of the peptides, and determine the structure around the beta-turn.

Amides↗
PubMed2004

A docking score function for estimating ligand-protein interactions: application to acetylcholinesterase inhibition.

Acetylcholinesterase (AChE) inhibition is an important research topic because of its wide range of associated health implications. A receptor-specific scoring function was developed herein for predicting binding affinities for human AChE (huAChE) inhibitors. This method entails a statistically trained weighted sum of electrostatic and van der Waals (VDW) interactions between ligands and the receptor residues. Within the 53 ligand training set, a strong correlation was found (R2 = 0.89) between computed and experimental inhibition constants. Leave-one-out cross-validation indicated high predictive power (Q2 = 0.72), and analysis of a separate 16-compound test set also produced very good correlation with experiment (R2 = 0.69). Scoring function analysis has permitted identification and characterization of important ligand-receptor interactions, producing a list of those residues making the most important electrostatic and VDW contributions within the main active site, gorge area, acyl binding pocket, and periferal site. These analyses are consistent with X-ray crystallographic and site-directed mutagenesis studies.

Acetylcholinesterase↗
PubMed2004

Utilization of hydrogen bonds to stabilize M-O(H) units: synthesis and properties of monomeric iron and manganese complexes with terminal oxo and hydroxo ligands.

Non-heme iron and manganese species with terminal oxo ligands are proposed to be key intermediates in a variety of biological and synthetic systems; however, the stabilization of these types of complexes has proven difficult because of the tendency to form oxo-bridged complexes. Described herein are the design, isolation, and properties for a series of mononuclear Fe(III) and Mn(III) complexes with terminal oxo or hydroxo ligands. Isolation of the complexes was facilitated by the tripodal ligand tris[(N'-tert-butylureaylato)-N-ethyl]aminato ([H(3)1](3-)), which creates a protective hydrogen bond cavity around the M(III)-O(H) units (M(III) = Fe and Mn). The M(III)-O(H) complexes are prepared by the activation of dioxygen and deprotonation of water. In addition, the M(III)-O(H) complexes can be synthesized using oxygen atom transfer reagents such as N-oxides and hydroxylamines. The [Fe(III)H(3)1(O)](2-) complex also can be made using sulfoxides. These findings support the proposal of a high valent M(IV)-oxo species as an intermediate during dioxygen cleavage. Isotopic labeling studies show that oxo ligands in the [M(III)H(3)1(O)](2-) complexes come directly from the cleavage of dioxygen: for [Fe(III)H(3)1(O)](2-) the nu(Fe-(16)O) = 671 cm(-1), which shifts 26 cm(-1) in [Fe(III)H(3)1((18)O)](2-) (nu(Fe-(18)O) = 645 cm(-1)); a nu(Mn-(16)O) = 700 cm(-1) was observed for [Mn(III)H(3)1((16)O)](2-), which shifts to 672 cm(-1) in the Mn-(18)O isotopomer. X-ray diffraction studies show that the Fe-O distance is 1.813(3) A in [Fe(III)H(3)1(O)](2-), while a longer bond is found in [Fe(III)H(3)1(OH)](-) (Fe-O at 1.926(2) A); a similar trend was found for the Mn(III)-O(H) complexes, where a Mn-O distance of 1.771(5) A is observed for [Mn(III)H(3)1(O)](2-) and 1.873(2) A for [Mn(III)H(3)1(OH)](-). Strong intramolecular hydrogen bonds between the urea NH groups of [H(3)1](3-) and the oxo and oxygen of the hydroxo ligand are observed in all the complexes. These findings, along with density functional theory calculations, indicate that a single sigma-bond exists between the M(III) centers and the oxo ligands, and additional interactions to the oxo ligands arise from intramolecular H-bonds, which illustrates that noncovalent interactions may replace pi-bonds in stabilizing oxometal complexes.

Ethylamines↗
PubMed2004

Differential inhibition of adenylyl cyclase isoforms and soluble guanylyl cyclase by purine and pyrimidine nucleotides.

Mammals express nine membranous adenylyl cyclase isoforms (ACs 1-9), a structurally related soluble guanylyl cyclase (sGC) and a soluble AC (sAC). Moreover, Bacillus anthracis and Bacillus pertussis produce the AC toxins, edema factor (EF), and adenylyl cyclase toxin (ACT), respectively. 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-[gamma-thio]triphosphate is a potent competitive inhibitor of AC in S49 lymphoma cell membranes. These data prompted us to study systematically the effects of 24 nucleotides on AC in S49 and Sf9 insect cell membranes, ACs 1, 2, 5, and 6, expressed in Sf9 membranes and purified catalytic subunits of membranous ACs (C1 of AC5 and C2 of AC2), sAC, sGC, EF, and ACT in the presence of MnCl(2). N-Methylanthraniloyl (MANT)-GTP inhibited C1.C2 with a K(i) of 4.2 nm. Phe-889 and Ile-940 of C2 mediate hydrophobic interactions with the MANT group. MANT-inosine 5'-[gamma-thio]triphosphate potently inhibited C1.C2 and ACs 1, 5, and 6 but exhibited only low affinity for sGC, EF, ACT, and G-proteins. Inosine 5'-[gamma-thio]triphosphate and uridine 5'-[gamma-thio]triphosphate were mixed G-protein activators and AC inhibitors. AC5 was up to 15-fold more sensitive to inhibitors than AC2. EF and ACT exhibited unique inhibitor profiles. At sAC, 2',5'-dideoxyadenosine 3'-triphosphate was the most potent compound (IC(50), 690 nm). Several MANT-adenine and MANT-guanine nucleotides inhibited sGC with K(i) values in the 200-400 nm range. UTP and ATP exhibited similar affinities for sGC as GTP and were mixed sGC substrates and inhibitors. The exchange of MnCl(2) against MgCl(2) reduced inhibitor potencies at ACs and sGC 1.5-250-fold, depending on the nucleotide and cyclase studied. The omission of the NTP-regenerating system from cyclase reactions strongly reduced the potencies of MANT-ADP, indicative for phosphorylation to MANT-ATP by pyruvate kinase. Collectively, AC isoforms and sGC are differentially inhibited by purine and pyrimidine nucleotides.

Adenylyl Cyclase Inhibitors↗
PubMed2003

Comparison of thioethers and sulfoxides as axial ligands for N-acetylmicroperoxidase-8: implications for oxidation of methionine-80 in cytochrome c.

Methionine-80 (Met-80) in mitochondrial cytochrome c (cyt c) can be oxidized to the corresponding sulfoxide by reactive oxygen species, a reaction of potential biological significance. As an approach to investigating how oxidation of Met-80 would influence its interactions with heme iron, we have examined binding of 2-(methylthio)ethanol (MTE) and dimethyl sulfoxide (DMSO), models for the side chains of Met and Met(SO), respectively, to ferrous and ferric N-acetylmicroperoxidase-8 (AcMP8). We find that DMSO coordinates 1.2 kcal/mol less strongly to Fe(III)-AcMP8 than does MTE, although both ligands form low-spin complexes. Comparison of spectroscopic data for the DMSO complex of Fe(III)-AcMP8 with published data for the Met(SO)-80 form of ferric cyt c allows us to conclude that Met(SO)-80 does not coordinate to iron in the latter. DMSO coordinates to Fe(II)-AcMP8 1.3 kcal/mol more strongly than does MTE, whereas Met-80 and Met(SO)-80 are reported to have approximately equal affinity for Fe(II) in cyt c. This result suggests that the steric environment near the heme iron in cyt c discriminates against coordination of Met(SO)-80. Vacuum quantum chemical density functional theory calculations confirm the greater affinity of the sulfoxide and show that coordination via oxygen is strongly favored. Resonance Raman spectroscopic data indicate that the preference for coordination via oxygen is maintained in solution. The computational data further indicate that the DMSO complex derives significant enthalpic stabilization from pi back-bonding but that iron to sulfur pi back-bonding does not make a significant contribution to bonding in the thioether complex.

Animals↗