Iron(II)–alkoxide and –aryloxide complexes of a tris(thioether)borate ligand: synthesis, molecular structures, and implications on the origin of instability of their iron(II)–catecholate counterpart

2021 ◽  
Vol 77 (9) ◽  
pp. 544-550
Author(s):  
Peng Wang ◽  
Glenn P. A. Yap ◽  
Charles G. Riordan
Keyword(s):  
Structural Information ◽  
Molecular Structures ◽  
Tridentate Ligand ◽  
Binding Modes ◽  
Catecholate Complex ◽  
Successful Isolation ◽  
Multinuclear Complexes ◽  
Synthetic Routes ◽  
Potential Use ◽  
Shed Light

The phenyltris[(tert-butylthio)methyl]borate ligand, [PhTt tBu], has been studied extensively as a platform for coordination, organometallic, and bioinorganic chemistry, especially with 3d metals. While [PhTt tBu]Co(3,5-DBCatH) (3,5-DBCatH is 3,5-di-tert-butylcatecholate), a CoII–monoanionic catecholate complex, was successfully isolated to model the active site of cobalt(II)-substituted homoprotocatechuate 2,3-dioxygenase (Co-HPCD) [Wang et al. (2019). Inorg. Chim. Acta, 488, 49–55], its iron(II) counterpart, [PhTt tBu]Fe(3,5-DBCatH), was not accessible via similar synthetic routes. Switching the nucleophile from catecholate to alkoxide or aryloxide, however, led to the successful isolation of three highly air-sensitive FeII–alkoxide and –aryloxide complexes, namely, (triphenylmethoxo){tris[(tert-butylsulfanyl)methyl]phenylborato-κ3 S,S′,S′′}iron(II), [Fe(C21H38BS3)(C19H15O)], (2), (2,6-dimethylphenolato){tris[(tert-butylsulfanyl)methyl]phenylborato-κ3 S,S′,S′′}iron(II), [Fe(C21H38BS3)(C8H9O)], (3), and bis{μ-tris[(tert-butylsulfanyl)methyl]phenylborato-κ3 S,S′:S′′}bis[(phenolato-κO)iron(II)] toluene disolvate, [Fe2(C21H38BS3)2(C6H5O)2]·2C7H8, (4). In the solid state, compounds (2) and (3) are monomeric, with [PhTt tBu] acting as a tridentate ligand. In contrast, compound (4) crystallizes as a dimeric complex, wherein each [PhTt tBu] ligand binds to an iron centre with two thioethers and binds to the other iron centre with the third thioether. The molecular structures of (2)–(4) demonstrate a diversity in the binding modes of [PhTt tBu] and highlight its potential use for assembling multinuclear complexes. In addition, the successful isolation of (2)–(4), as well as the structural information of a [PhTt tBu] modification product, namely, bis{μ-tris[(tert-butylsulfanyl)methyl](2-oxidophenolato)borato-κO,O′,S,S′:O′}dicobalt(II), [Co2(C21H37BO2S3)2], (5), obtained from the reaction of [PhTt tBu]CoCl with potassium monoanionic catecholate, shed light on the origin of the instability of [PhTt tBu]Fe(3,5-DBCatH).

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

2020 ◽  
Vol 24 (21) ◽  
pp. 2475-2497
Author(s):  
Andrea Verónica Rodríguez-Mayor ◽  
German Jesid Peralta-Camacho ◽  
Karen Johanna Cárdenas-Martínez ◽  
Javier Eduardo García-Castañeda
Keyword(s):  
Chemical Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Heterogeneous Environments ◽  
Phase Synthesis ◽  
Low Concentrations ◽  
Biological Sources ◽  
Synthetic Routes ◽  
The Impact ◽  
Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

1,4-Diazepines: A Review on Synthesis, Reactions and Biological Significance

2019 ◽  
Vol 16 (5) ◽  
pp. 709-729 ◽  
Author(s):  
Muhammad A. Rashid ◽  
Aisha Ashraf ◽  
Sahibzada S. Rehman ◽  
Shaukat A. Shahid ◽  
Adeel Mahmood ◽  
...  
Keyword(s):  
Biological Activities ◽  
Biological Significance ◽  
Biological Evaluation ◽  
Wide Range ◽  
Pharmaceutical Industries ◽  
Biological Aspects ◽  
Synthetic Routes ◽  
Biological Attributes ◽  
Synthesis Reactions ◽  
Potential Use

Background:1,4-Diazepines are two nitrogen containing seven membered heterocyclic compounds and associated with a wide range of biological activities. Due to its medicinal importance, scientists are actively involved in the synthesis, reactions and biological evaluation of 1,4-diazepines since number of decades.Objective:The primary purpose of this review is to discuss the synthetic schemes and reactivity of 1,4- diazepines. This article also describes biological aspects of 1,4-diazepine derivatives, that can be usefully exploited for the pharmaceutical sector.Conclusion:This review summarizes the abundant literature on synthetic routes, chemical reactions and biological attributes of 1,4-diazepine derivatives. We concluded that 1,4-diazepines have significant importance due to their biological activities like antipsychotic, anxiolytic, anthelmintic, anticonvulsant, antibacterial, antifungal and anticancer. 1,4-diazepine derivatives with significant biological activities could be explored for potential use in the pharmaceutical industries.

Novel Synthetic Routes to s-Block Metal 2,5-Diphenylphospholides and Crystal Structures of the Bis(tetrahydrofuran) Complexes of the Potassium, Calcium, and Strontium Derivatives

2009 ◽  
Vol 64 (11-12) ◽  
pp. 1360-1368 ◽  
Author(s):  
Katja Wimmer ◽  
Christin Birg ◽  
Robert Kretschmer ◽  
Tareq M.A. Al-Shboul ◽  
Helmar Görls ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Chain Structure ◽  
Molecular Structures ◽  
Metathesis Reaction ◽  
Sandwich Complex ◽  
Coordination Site ◽  
Metal Atoms ◽  
Synthetic Routes ◽  
A Chain

The reduction of 1,4-diphenyl-1,4-bis(diphenylphosphanyl)buta-1,3-diene (1) (1,4-diphenyl- NUPHOS) with potassium in THF yields bis(THF)potassium 2,5-diphenylphospholide (2) which crystallizes with a chain structure. The metathesis reaction of 2 with the iodides of calcium, strontium, and barium leads to the formation of [bis(THF)calcium bis(2,5-diphenylphospholide)] (3), [bis(THF)strontium bis(2,5-diphenylphospholide)] (4), and [bis(THF)barium bis(2,5-diphenylphospholide)] (5). The reaction of M{P(H)SiiPr3}2 with diphenylbutadiyne in THF also leads to the formation of the 2,5-diphenylphospholides of calcium (3), strontium (4), and barium (5). The molecular structures of 2 to 4 are discussed. The environment of the metal atoms is very similar in all these compounds: The metal atoms show an η5 coordination to the phospholide rings forming a bent sandwich complex. The open coordination site is occupied by two THF molecules

scholarly journals Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Matthew J. Belousoff ◽  
Zohar Eyal ◽  
Mazdak Radjainia ◽  
Tofayel Ahmed ◽  
Rebecca S. Bamert ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Structural Information ◽  
Structural Basis ◽  
Common Mechanism ◽  
Resistance Mutations ◽  
Antimicrobial Drugs ◽  
Linezolid Resistance ◽  
Drug Modification ◽  
Antibiotic Resistance Mutations ◽  
Shed Light

ABSTRACT An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of Staphylococcus aureus. This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 Å away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site. IMPORTANCE The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent Staphylococcus aureus resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821–832, 2015, https://doi.org/10.1038/nrd4675 ). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance. IMPORTANCE The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent Staphylococcus aureus resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821–832, 2015, https://doi.org/10.1038/nrd4675 ). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance.

scholarly journals Neural Upscaling from Residue-Level Protein Structure Networks to Atomistic Structures

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1788
Author(s):  
Vy T. Duong ◽  
Elizabeth M. Diessner ◽  
Gianmarc Grazioli ◽  
Rachel W. Martin ◽  
Carter T. Butts
Keyword(s):  
Protein Structure ◽  
Intrinsically Disordered Proteins ◽  
Dynamic Models ◽  
Structural Information ◽  
Coarse Graining ◽  
Molecular Structures ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Scalable Network ◽  
Atomic Coordinates

Coarse-graining is a powerful tool for extending the reach of dynamic models of proteins and other biological macromolecules. Topological coarse-graining, in which biomolecules or sets thereof are represented via graph structures, is a particularly useful way of obtaining highly compressed representations of molecular structures, and simulations operating via such representations can achieve substantial computational savings. A drawback of coarse-graining, however, is the loss of atomistic detail—an effect that is especially acute for topological representations such as protein structure networks (PSNs). Here, we introduce an approach based on a combination of machine learning and physically-guided refinement for inferring atomic coordinates from PSNs. This “neural upscaling” procedure exploits the constraints implied by PSNs on possible configurations, as well as differences in the likelihood of observing different configurations with the same PSN. Using a 1 μs atomistic molecular dynamics trajectory of Aβ1–40, we show that neural upscaling is able to effectively recapitulate detailed structural information for intrinsically disordered proteins, being particularly successful in recovering features such as transient secondary structure. These results suggest that scalable network-based models for protein structure and dynamics may be used in settings where atomistic detail is desired, with upscaling employed to impute atomic coordinates from PSNs.

scholarly journals Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies

2021 ◽  
Vol 22 (22) ◽  
pp. 12320
Author(s):  
Xianjin Xu ◽  
Xiaoqin Zou
Keyword(s):  
Molecular Similarity ◽  
Complex Structure ◽  
Binding Mode ◽  
Molecular Structures ◽  
Complex Structures ◽  
Binding Modes ◽  
Ligand Complex ◽  
Systematic Analysis ◽  
Binding Mode Prediction ◽  
Similarity Principle

The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein–ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein–ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.

scholarly journals Water-Soluble Bismuth(III) Polynuclear Tyrosinehydroximate Metallamacrocyclic Complex: Structural Parallels to Lanthanide Metallacrowns

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4379
Author(s):  
Marina A. Katkova ◽  
Grigory Y. Zhigulin ◽  
Roman V. Rumyantcev ◽  
Galina S. Zabrodina ◽  
Vladimir R. Shayapov ◽  
...  
Keyword(s):  
Electronic Structures ◽  
Structural Parameters ◽  
Molecular Structures ◽  
Water Soluble ◽  
Thermochromic Properties ◽  
Donor Acceptor ◽  
Coordination Ability ◽  
Synthetic Routes ◽  
Complex Structural

Recently there has been a great deal of interest and associated research into aspects of the coordination chemistry of lanthanides and bismuth—elements that show intriguing common features. This work focuses on the synthesis and characterization of a novel bismuth(III) polynuclear metallamacrocyclic complex derived from aminohydroxamic acid, in order to compare the coordination ability of Bi3+ with the similarly sized La3+ ions. A polynuclear tyrosinehydroximate Bi(OH)[15-MCCu(II)Tyrha-5](NO3)2 (1) was obtained according to the synthetic routes previously described for water-soluble Ln(III)-Cu(II) 15-MC-5 metallacrowns. Correlations between structural parameters of Bi(III) and Ln(III) complexes were analyzed. DFT calculations confirmed the similarity between molecular structures of the model bismuth(III) and lanthanum(III) tyrosinehydroximate 15-metallacrowns-5. Analysis of the electronic structures revealed, however, stronger donor-acceptor interactions between the central ion and the metallamacrocycle in the case of the lanthanum analogue. Thermochromic properties of 1 were studied.

Fluorosulfates of palladium

1977 ◽  
Vol 55 (13) ◽  
pp. 2473-2477 ◽  
Author(s):  
K. C. Lee ◽  
F. Aubke
Keyword(s):  
Ground State ◽  
Diffuse Reflectance ◽  
Magnetic Measurements ◽  
Structural Information ◽  
Tridentate Ligand ◽  
Ligand Field ◽  
Polymeric Structure ◽  
Octahedral Environment ◽  
Fluorosulfate Group ◽  
Ligand Field Parameter

The syntheses of Pd(SO3F)2 and Pd(SO3F)3 by the reactions of palladium with BrOSO2F and S2O6F2 are described. Structural information on both compounds is based on infrared, Raman, diffuse reflectance, and electronic mull spectra as well as magnetic measurements from ∼300 to ∼100 K. Palladium bisfluorosulfate is found to have a polymeric structure with the fluorosulfate group acting as a tridentate ligand. As a consequence, an octahedral environment is found for Pd2+ with a 3A2g ground state, a µeff298 value of 3.39 BM and the ligand field parameter Dq = 1177 cm−1 and B = 633 cm−1. Pd(SO3F)3 is best regarded as PdII[PdIV(SO3F)6].

scholarly journals Caffeine inhibits Notum activity by binding at the catalytic pocket

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuguang Zhao ◽  
Jingshan Ren ◽  
James Hillier ◽  
Weixian Lu ◽  
Edith Yvonne Jones
Keyword(s):  
Surface Plasmon Resonance ◽  
High Resolution ◽  
Structural Information ◽  
Therapeutic Benefit ◽  
Wnt Signalling ◽  
Binding Modes ◽  
Natural Substrate ◽  
Small Molecule Inhibition ◽  
Minor Metabolite ◽  
Wnt Ligands

Abstract Notum inhibits Wnt signalling via enzymatic delipidation of Wnt ligands. Restoration of Wnt signalling by small molecule inhibition of Notum may be of therapeutic benefit in a number of pathologies including Alzheimer’s disease. Here we report Notum activity can be inhibited by caffeine (IC50 19 µM), but not by demethylated caffeine metabolites: paraxanthine, theobromine and theophylline. Cellular luciferase assays show Notum-suppressed Wnt3a function can be restored by caffeine with an EC50 of 46 µM. The dissociation constant (Kd) between Notum and caffeine is 85 µM as measured by surface plasmon resonance. High-resolution crystal structures of Notum complexes with caffeine and its minor metabolite theophylline show both compounds bind at the centre of the enzymatic pocket, overlapping the position of the natural substrate palmitoleic lipid, but using different binding modes. The structural information reported here may be of relevance for the design of more potent brain-accessible Notum inhibitors.

Sign in / Sign up

Export Citation Format

Share Document