Steric Influence Research Articles

Direct SN2 or SN2X Manifold─Mechanistic Study of Ion-Pair-Catalyzed Carbon(sp3)-Carbon(sp3) Bond Formation.

Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)-carbon(sp3) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent SN2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an SN2 pathway and connect to thermodynamically stable intermediates. Extensive computational screening modeling was then done on various substrate combinations designed to study the steric influence and to understand the mechanistic rationale, and calculations reveal that sterically congested substrates prefer the SN2X manifold over SN2. Different halides as leaving groups were also screened, and it was found that the reactivity increases in the order of I > Br > Cl > F, in agreement with the strength of C-X bonds. However, DFT modeling suggests that chlorides can be a viable substrate for the SN2X process, which should be further explored experimentally. ONIOM calculations on the full catalyst model predicted the correct stereochemical outcome, and further catalyst screening with cationic Me4N+ and K+ predicted that pentanidium is still the choice for SN2X C-C bond formation.

An investigation into the coordination chemistry of tripodal “click” triazole ligands with Mn, Ni, Co and Zn ions

The steric influences of the triazole side chains in two tripodal chelating ligands tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) and tris[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]amine (TPTA) are explored through structural studies of four new mononuclear d-block metal complexes. The manganese(II) complex [Mn(TPTA)2](ClO4)2·H2O 1 includes two TPTA ligands each coordinated in a tridentate fashion to give an unusual trigonal prismatic coordination geometry with two non-coordinated pendant triazole groups which engage in weak hydrogen bonding interactions. [Ni(TBTA)(OH2)Cl]Cl·3H2O·MeCN 2 contains an octahedral nickel(II) centre bound by a tetradentate TBTA ligand along with aqua and chloride ligands, where the significant degree of lattice solvation leads to an extensive hydrogen bonding network linking complexes through hexa-aqua water clusters. The mononuclear copper(II) complex [Cu(TPTA)Cl2]·MeCN 3 contains no classical hydrogen bond donors but instead intermolecular aggregation takes place through chelating CH···Cl hydrogen bonds involving the acidic triazole CH groups which leads to close association of adjacent complexes. The zinc complex [Zn(TPTA)Cl]2[ZnCl4]·MeOH 4, in which cationic [Zn(TPTA)Cl]+ species are accompanied by tetrachlorozincate anions, exhibits a tris-triazole chelating coordination geometry for the TPTA ligand and associates through tetrameric π···π stacking interactions despite the positive charge present on each species. Structural analysis of these complexes, supported by solution-state mass spectrometry, NMR spectroscopic and magnetic susceptibility measurements, where applicable, provides new insights into the breadth of coordination geometries and intermolecular packing modes available to this important class of chelating ligand.

Energetic Basis and Design of Enzyme Function Demonstrated Using GFP, an Excited-State Enzyme.

The past decades have witnessed an explosion of de novo protein designs with a remarkable range of scaffolds. It remains challenging, however, to design catalytic functions that are competitive with naturally occurring counterparts as well as biomimetic or nonbiological catalysts. Although directed evolution often offers efficient solutions, the fitness landscape remains opaque. Green fluorescent protein (GFP), which has revolutionized biological imaging and assays, is one of the most redesigned proteins. While not an enzyme in the conventional sense, GFPs feature competing excited-state decay pathways with the same steric and electrostatic origins as conventional ground-state catalysts, and they exert exquisite control over multiple reaction outcomes through the same principles. Thus, GFP is an "excited-state enzyme". Herein we show that rationally designed mutants and hybrids that contain environmental mutations and substituted chromophores provide the basis for a quantitative model and prediction that describes the influence of sterics and electrostatics on excited-state catalysis of GFPs. As both perturbations can selectively bias photoisomerization pathways, GFPs with fluorescence quantum yields (FQYs) and photoswitching characteristics tailored for specific applications could be predicted and then demonstrated. The underlying energetic landscape, readily accessible via spectroscopy for GFPs, offers an important missing link in the design of protein function that is generalizable to catalyst design.

Steric influences on the photophysical properties of pyrene-based derivatives; mechanochromism and their pH-responsive ability

Steric effects have attracted great attention in the fields of synthetic chemistry, spectroscopy, crystallography, as well as surface chemistry. Herein, two pyrene-based compounds with different cyclic ketones acting as a bridge are presented and the influence of the steric effects on the luminescent and molecular packing is investigated. Both luminogens display different optical properties both in dilute and aggregate states. Notably, the pyrene-based cyclopentanone (2) possesses a non-aggregation-induced emission (AIE) feature, whilst pyrene-based cyclohexanone (3) is AIE-active due to steric effects. Furthermore, the mechanochromism properties and pH-responsive ability of both pyrenes are investigated by use of fluorescence and XRD technologies. The present work provides insight into how steric effects impact on the molecular conformations and optical properties in these new pyrene-based AIE luminogen systems.

Bisamidate-functionalized NHC ligands: Electronic and steric influences of N-substituents on the bisamidate moieties

Bis-anionic tethered NHC ligands have widely served as stable and useful catalysts. The properties of anionic donor sites make them useful for the tuning of metal complexes with the NHC ligands, and since amidate ligands can be functionalized on their nitrogen elements, they also have been applied as catalysts. There has been, however, a paucity of investigations into the influences of various N-substituents on bisamidate portions within bis-amidate functionalized NHCs. In this study, we used original NHCs, which we refer to as DHASIs, to synthesize various bisamide functionalized NHC pincer ligand precursors, and their Pd complexes also were successfully obtained. The structures of the synthesized complexes were unambiguously confirmed via XRD study, which showed that the N-substituents had a structural affect via the coordination modes of the resultant complexes. We applied the obtained pincer complexes to a Suzuki Miyaura coupling reaction and found that the strong Lewis basicity of the anionic N donors improved the catalytic performance of Pd–NCN pincer complexes.

Effect of N-benzyl group in indole scaffold of thiosemicarbazones on the biological activity of their Pd(II) complexes: DFT, biomolecular interactions, in silico docking, ADME and cytotoxicity studies

A series of N-benzyl substituted indole-based thiosemicarbazone (TSC) ligands (L4-L6) and palladium(II) TSC complexes, [Pd(L)2] (1–6) (L = monoanionic bidentate un/N-substituted indole-based TSC ligand) have been synthesized and characterized using analytical and spectroscopic tools. The exact molecular structures of L4-L6 and the complexes (2–4 and 6) were ascertained by single-crystal X-ray diffraction (XRD) method. Spectroscopic and crystallographic studies indicated that Pd(II) ion was coordinated with TSCs as monobasic bidentate ligands, forming two five-membered rings with square planar geometry. The effect of N-benzyl substitution in indole scaffold of TSCs in the complexes was studied using DFT method, and structure–activity relationships (SAR) were explored. The in silico ADME properties of the ligands and their complexes were thoroughly analyzed with respect to their lipophilicity and oral bioavailability. The complexes (1–6) exhibited strong intercalation with calf thymus DNA (CT DNA), which was examined by absorption/emission spectroscopic titrations and viscosity measurements. Similarly, the interaction of bovine serum albumin (BSA) with complexes examined using spectroscopic methods showed a strong binding between them. A better picture of various possible interactions was acquired from the molecular docking of the complexes with the targets like DNA, BSA, DNA Topoisomerase II and CASP3. In addition, in vitro cytotoxicity of the complexes was screened against two cancer (HeLa-S3 and A549) and one normal (IMR-90) cell lines. It was learnt that the N-benzyl substitution in the indole system inactivated the whole molecule by diminishing its anticancer activity. The unsubstituted indole TSC complex (2) displayed significant activity towards HeLa-S3 cells, and the results were compared with those of cisplatin. Beneficially, the active complex showed less toxicity against IMR-90 normal cells. Further, the results of AO-EB staining studies indicated that the complexes induced cell death via apoptosis pathway. The steric influence of the substituted indole moiety, its limited electronic effects and lesser stability in aqueous systems retarded the Pd(II) complexes of N-benzyl substituted indole TSCs from exhibiting their biological activities.

Synthesis of substituted (N,C) and (N,C,C) Au(III) complexes: the influence of sterics and electronics on cyclometalation reactions.

Cyclometalated Au(III) complexes are of interest due to their catalytic, medicinal, and photophysical properties. Herein, we describe the synthesis of derivatives of the type (N,C)Au(OAcF)2 (OAcF = trifluoroacetate) and (N,C,C)AuOAcF by a cyclometalation route, where (N,C) and (N,C,C) are chelating 2-arylpyridine ligands. The scope of the synthesis is explored by substituting the 2-arylpyridine core with electron donor or acceptor substituents at one or both rings. Notably, a variety of functionalized Au(III) complexes can be obtained in one step from the corresponding ligand and Au(OAc)3, eliminating the need for organomercury intermediates, which is commonly reported for similar syntheses. The influence of substituents in the ligand backbone on the resulting complexes was assessed using DFT calculations, 15N NMR spectroscopy and single-crystal X-ray diffraction analysis. A correlation between the electronic properties of the (N,C) ligands and their ability to undergo cyclometalation was found from experimental studies combined with natural charge analysis, suggesting the cyclometalation at Au(III) to take place via an electrophilic aromatic substitution-type mechanism. The formation of Au(III) pincer complexes from tridentate (N,C,C) ligands was investigated by synthesis and DFT calculations, in order to assess the feasibility of C(sp3)-H bond activation as a synthetic pathway to (N,C,C) cyclometalated Au(III) complexes. It was found that C(sp3)-H bond activation is feasible for ligands containing different alkyl groups (isopropyl and ethyl), although the C-H activation is less energetically favored compared to a ligand containing tert-butyl groups.

Steric influence on solvate formation – a comparison of resorcylic acid and two brominated derivatives

Unbalanced steric bulk can lead to increased solvate formation as shown in non-, mono- and dibrominated resorcylic acid.

Abnormal NHC ruthenium catalysts: mechanistic investigations of their preparation and steric influence on catalytic performance

Preparation of bis-aNHC Ru catalysts, identification of formation intermediates and application in transfer hydrogenation and Oppenauer-type oxidation, observing an inversion in activity appearing to be dependent on steric hindrance.

Unusual {⋯HNC2O⋯HCnO}, n = 1 or 2, synthons predominate in the molecular packing of one-dimensional coordination polymers, {Cd[S2P(OR)2]2(3LH2)}n, for R = Me and Et, but are precluded when R = i-Pr; 3LH2 = N,N′-bis(3-pyridylmethyl)oxalamide

The electronic & steric influence of the dithiophosphate-R groups mediates the formation of unprecedented supramolecular synthons.

Biomolecular Binding under Confinement: Statistical Predictions of Steric Influence in Absence of Long-Distance Interactions.

We propose a theoretical model for the influence of confinement on biomolecular binding at the single-molecule scale at equilibrium, based on the change of the number of microstates (localization and orientation) upon reaction. Three cases are discussed: DNA sequences shorter and longer than the single strain DNA Kuhn length and spherical proteins, confined into a spherical container (liposome, droplet, etc.). The influence of confinement is found to be highly dependent on the molecular structure and significant for large molecules (relative to container size).

Ligand Influence on Structural and Spectroscopic Properties of Beryllium Oxocarboxylates.

Aluminum-based adjuvants for vaccines and beryllium ions interact with the same immune receptor. The Be4O core, which is also found in beryllium oxocarboxylates, has been proposed to be the binding species in the latter case. However, this is not proven due to a lack of suitable probes for the Be4O moiety. Therefore, a versatile synthetic route to beryllium oxocarboxylates has been developed to investigate the steric and electronic influence of the ligands onto their molecular and spectroscopic properties. The oxocarboxylates exhibit extremely narrow line widths in 9Be NMR spectroscopy, and the chemical shift is only influenced by the sterics of the ligands. The mean variation of the atomic distances in the central Be4O building block is extremely small over all investigated compounds, and even the C-C distances are only little perturbed by the properties of the ligands. Vibrational spectroscopy showed Be-O bands; however, further distinctions could not be drawn.

Tin(II) Ureide Complexes: Synthesis, Structural Chemistry, and Evaluation as SnO Precursors

In an attempt to tailor precursors for application in the deposition of phase pure SnO, we have evaluated a series of tin (1-6) ureide complexes. The complexes were successfully synthesized by employing N,N'-trialkyl-functionalized ureide ligands, in which features such as stability, volatility, and decomposition could be modified with variation of the substituents on the ureide ligand in an attempt to find the complex with the ideal electronic, steric, or coordinative properties, which determine the fate of the final products. The tin(II) ureide complexes 1-6 were synthesized by direct reaction [Sn{NMe2}2] with aryl and alkyl isocyanates in a 1:2 molar ratio. All the complexes were characterized by NMR spectroscopy as well as elemental analysis and, where applicable, thermogravimetric (TG) analysis. The single-crystal X-ray diffraction studies of 2, 3, 4, and 6 revealed that the complexes crystallize in the monoclinic space group P2(1)/n (2 and 4) or in the triclinic space group P-1 (3 and 6) as monomers. Reaction with phenyl isocyanate results in the formation of the bimetallic species 5, which crystallizes in the triclinic space group P-1, a consequence of incomplete insertion into the Sn-NMe2 bonds, versus mesityl isocyanate, which produces a monomeric double insertion product, 6, under the same conditions, indicating a difference in reactivity between phenyl isocyanate and mesityl isocyanate with respect to insertion into Sn-NMe2 bonds. The metal centers in these complexes are all four-coordinate, displaying either distorted trigonal bipyramidal or trigonal bipyramidal geometries. The steric influence of the imido-ligand substituent has a clear effect on the coordination mode of the ureide ligands, with complexes 2 and 6, which contain the cyclohexyl and mesityl ligands, displaying κ2-O,N coordination modes, whereas κ2-N,N' coordination modes are observed for the sterically bulkier tert-butyl and adamantyl derivatives, 3 and 4. The thermogravimetric analysis of the complexes 3 and 4 exhibited excellent physicochemical properties with clean single-step curves and low residual masses in their TG analyses suggesting their potential utility of these systems as MOCVD and ALD precursors.

Steric Influence on Reactions of Benzyl Potassium Species with CO.

Reactions of benzyl potassium species with CO are shown to proceed via transient carbene‐like intermediates that can undergo either dimerization or further CO propagation. In a sterically unhindered case, formal dimerization of the carbene is the dominant reaction pathway, as evidenced by the isolation of ((Ph3SiO)(PhCH2)C)2 2 and PhCH2C(O)CH(OH)CH2Ph 3. Reactions with increasingly sterically encumbered reagents show competitive reaction pathways involving intermolecular dimerization leading to species analogous to 2 and 3 and those containing newly‐formed five‐membered rings tBu2C6H2(C(OSiR3)C(OSiR3)CH2) (R=Me 6, Ph 7). Even further encumbered reagents proceed to either dimerize or react with additional CO to give a ketene‐like intermediates, thus affording a 7‐membered tropolone derivative 14 or the dione (3,5‐tBu2C6H3)3C6H2CH2C(O))2 15.

Investigation of type-I conformations of A2B4-[26]hexaphyrins(1.1.1.1.1.1) bearing strongly electron-withdrawing aryl substituents at 5,20-positions

The dumbbell-shaped type-I conformation is the inherent structure of the [26]hexaphyrin(1.1.1.1.1.1) framework without any perturbations from its peripheral substituents. Conversely, the rectangular type-II conformation can be regarded as a more general structure seen in stable [26]hexaphyrins(1.1.1.1.1.1) because of not only the synthetic limitations but also the steric influences related to the meso-aryl substituents. In this study, the synthesis of [26]hexaphyrins(1.1.1.1.1.1) bearing a series of electron-withdrawing groups and their conformational characterizations were investigated. The 1H NMR spectra showed that [26]hexaphyrin with 3,5-dinitrophenyl groups at the 5,20-positions was obtained as the sole type-I conformer, whereas most other [26]hexaphyrins are in equilibrium between type-I, type-II, and type-II[Formula: see text] conformers. Moreover, UV-vis absorption measurements revealed that type-I conformations can utilize the electronic features of their 5,20-substituents owing to their relatively co-planar arrangements with the macrocycles.

Syntheses and properties of mononuclear cobalt-dioxolene complexes with the ancillary ligand containing bulky quinoline rings – Electronic state manipulation of the complexes by steric effect

Two types of mononuclear cobalt complexes with two ancillary ligands containing isoquinoline groups and 3, 5-di-tert-butylcatechol (3, 5-DBCat) were synthesized. The crystal structures and spectroscopic, electrochemical, and magnetic properties of these complexes and complexes with ancillary ligands containing multiple quinoline groups were compared to clarify the steric effect of quinoline derivatives around the cobalt center. In particular, a comparison of the crystal structures of the mononuclear cobalt complexes containing tris(2-quinolylmethyl)amine (tqa) and tris(3-isoquinolylmethyl)amine (isotqa) as ancillary ligands, each of which has three isoquinoline and three quinoline rings, showed that the isotqa complex was less congested than the tqa complex around the cobalt center. As a result, the tqa complex contains Co (II), whereas the isotqa complex has the stable Co (III) electronic state due to the stronger ligand field. In this report, the steric influence of ancillary ligand substituents on the electronic states of complexes is clarified from several perspectives such as spectroscopic, electrochemical and magnetic properties.

TEMPO‐Modified Polymethacrylates as Mediators in Electrosynthesis – Redox Behavior and Electrocatalytic Activity toward Alcohol Substrates

AbstractHomogeneous catalysts (“mediators”) are useful for tuning selectivity in organic electrosynthesis. However, they can have a negative impact on the overall mass and energy balance if used only once or recycled inefficiently. In a previous work, we introduced the polymediator concept, in which soluble redox‐active polymers catalyze the electrochemical reaction, allowing for recovery by dialysis or pressure‐driven membrane filtration. Using anodic alcohol oxidation as a test case, it was shown that TEMPO‐modified polymethacrylates (TPMA) can serve as efficient and reusable mediators. In the present study, the properties of a TPMA sample with well‐defined molecular weight distribution were studied using cyclic voltammetry and compared to low‐molecular TEMPO species. The non‐catalytic profiles of TPMA are shaped by diffusive and adsorptive processes, whereby the latter only become pronounced at low mediator concentrations and high scan rates. Electrocatalytic studies suggest that under the applied conditions, TPMA‐catalyzed alcohol oxidation is a predominantly homogeneous process. The homogeneous kinetics are determined rather by the mediator potential than by steric influences of the polymer backbone.

Mechanistic study of enantioselective Pd-catalyzed C(sp3)-H activation of thioethers involving two distinct stereomodels.

Enantioselective C(sp3)-H activation has gained considerable attention from the synthetic chemistry community. Despite the intense interest in these reactions, the mechanisms responsible for enantioselection are still vague. In the course of the development of aryl thioether-directed C(sp3)-H arylation, we noticed extreme variation in sensitivity of two substrate classes to substituent effects of ligands and directing groups: whereas 3-pentyl sulfides (prochiral α-center) responded positively to substitution on ligands and directing groups, isobutyl sulfides (prochiral β-center) were entirely insensitive. Quantitative structure selectivity relationship (QSSR) analyses of directing group and ligand substitution and the development of a new class of mono-N-acetyl protected amino anilamide (MPAAn) ligands led to high enantiomeric ratios (up to 99:1) for thioether-directed C(sp3)-H arylation. Key to the realization of this method was the exploitation of transient chirality at sulfur, which relays stereochemical information from the ligand backbone to enantiotopic carbons of the substrate in a rate- and enantio-determining cyclometallation deprotonation. The absolute stereochemistry of the products for these two substrates were revealed to be opposite. DFT evaluation of all possible diastereomeric transition states confirmed initial premises that guided rational ligand and directing group design. The implications of this study will assist in the further development of enantioselective C(sp3)-H activation, namely by highlighting the non-innocence of directing groups, distal steric influences, and the delicate interplay between steric Pauli repulsion and London dispersion in enantioinduction.

Simulations of Ionic Liquids Confined in Surface-Functionalized Nanoporous Carbons: Implications for Energy Storage

Porous carbons are used in a wide range of applications, including electrochemical double-layer capacitors for energy storage, in which electrolyte ion properties under confinement are crucial for the performance of the systems. While many synthesis techniques lead to the presence of surface functional groups, their effect on the adsorption and diffusion of electrolyte ions is still poorly understood. In this study, we investigate the effect of surface chemistry on the dynamical and structural properties of adsorbed ions through molecular dynamics simulations of a neat ionic liquid in contact with several zeolite-templated carbons, used here as model materials for the larger range of existing ordered microporous carbons. The steric and specific influence of functional groups is explored using three structures: a structure without any functional groups; a structure with ester, hydroxyl, anhydride acid, and carboxyl functional groups; and a structure where the oxygen and hydrogen atoms are replaced by carbon atoms. We calculate quantities of adsorbed ions and diffusion coefficients, which show variations with the addition of functional groups in agreement with experimental data for similar systems. We observe that the functionalization has a limited impact on the structure of the confined electrolyte but affects the ion mobility more markedly, and that the relative importance of the structure and chemical nature of the functional groups is not the same depending on the ion type and property considered.

Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids

This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two α-hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) resulted in the formation of cocrystals or salts of composition (inh)·(H2ga) (1) and [Hinh]+[Hma]–·(H2ma) (2) when reacted with isoniazid. An N′-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh)·1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions.