Steric Influence Research Articles

Synthesis, characterization, catalytic and biological application of half-sandwich ruthenium complexes bearing hemilabile (κ2-C,S)-thioether-functionalised NHC ligands.

A series of cationic Ru(ii)(η6-p-cymene) complexes with thioether-functionalised N-heterocyclic carbene ligands have been prepared and fully characterized. Steric and electronic influence of the R thioether substituent on the coordination of the sulfur atom was investigated. The molecular structure of three of them has been determined by means of X-ray diffractrometry and confirmed the bidentate (κ2-C,S) coordination mode of the ligand. Interestingly, only a single diastereomer, as an enantiomeric couple, was observed in the solid state for complexes 1c, 1i and 1j. DFT calculations established a low energy inversion barrier between the two diastereomers through a sulfur pyramidal inversion pathway with R donating group while a dissociative/associative mechanism is more likely with R substituents that contain electron withdrawing group, thus suggesting that the only species observed by the 1H-NMR correspond to an average resonance position of a fluxional mixtures of isomers. All these complexes were found to catalyse the oxydant-free double dehydrogenation of primary amine into nitrile. Ru complex bearing NHC-functionalised S-tBu group was further investigated in a wide range of amines and was found more selective for alkyl amine substrates than for benzylamine derivatives. Finally, preliminary results of the biological effects on various human cancer cells of four selected Ru complexes are reported.

An Investigation of Electrocatalytic CO2 Reduction Using a Manganese Tricarbonyl Biquinoline Complex.

The subject of this study [fac-Mn(bqn)(CO)3(CH3CN)]+ (bqn = 2,2′-biquinoline), is of particular interest because the bqn ligand exhibits both steric and electronic influence over the fundamental redox properties of the complex and, consequently, its related catalytic properties with respect to the activation of CO2. While not a particularly efficient catalyst for CO2 to CO conversion, in-situ generation and activity measurements of the [fac-Mn(bqn)(CO)3]− active catalyst allows for a better understanding of ligand design at the Mn center. By making direct comparisons to the related 2,2′-bipyridyl (bpy), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (dmphen) ligands via a combination of voltammetry, infrared spectroelectrochemistry, controlled potential electrolysis and computational analysis, the role of steric vs. electronic influences on the nucleophilicity of Mn-based CO2 reduction electrocatalysts is discussed.

Relaxation Dispersion NMR to Reveal Fast Dynamics in Brønsted Acid Catalysis: Influence of Sterics and H-Bond Strength on Conformations and Substrate Hopping.

NMR provides both structural and dynamic information, which is key to connecting intermediates and to understanding reaction pathways. However, fast exchanging catalytic intermediates are often inaccessible by conventional NMR due its limited time resolution. Here, we show the combined application of the 1H off-resonance R1ρ NMR method and low temperature (185–175 K) to resolve intermediates exchanging on a μs time scale (ns at room temperature). The potential of the approach is demonstrated on chiral phosphoric acid (CPA) catalysts in their complexes with imines. The otherwise inaccessible exchange kinetics of the E-I ⇌ E-II imine conformations and thermodynamic E-I:E-II imine ratios inside the catalyst pocket are experimentally determined and corroborated by calculations. The E-I ⇌ E-II exchange rate constants (kex185 K) for different catalyst–substrate binary complexes varied between 2500 and 19 000 s–1 (τex = 500–50 μs). Theoretical analysis of these exchange rate constants revealed the involvement of an intermediary tilted conformation E-III, which structurally resembles the hydride transfer transition state. The main E-I and E-II exchange pathway is a hydrogen bond strength dependent tilting–switching–tilting mechanism via a bifurcated hydrogen bond as a transition state. The reduction in the sterics of the catalyst showed an accelerated switching process by at least an order of magnitude and enabled an additional rotational pathway. Hence, the exchange process is mainly a function of the intrinsic properties of the 3,3′-substituents of the catalyst. Overall, we believe that the present study opens a new dimension in catalysis via experimental access to structures, populations, and kinetics of catalyst–substrate complexes on the μs time scale by the 1H off-resonance R1ρ method.

How Metal Ion Lewis Acidity and Steric Properties Influence the Barrier to Dioxygen Binding, Peroxo O-O Bond Cleavage, and Reactivity.

Herein we quantitatively investigate how metal ion Lewis acidity and steric properties influence the kinetics and thermodynamics of dioxygen binding versus release from structurally analogous Mn-O2 complexes, as well as the barrier to Mn peroxo O-O bond cleavage, and the reactivity of Mn oxo intermediates. Previously we demonstrated that the steric and electronic properties of MnIII-OOR complexes containing N-heterocyclic (NAr) ligand scaffolds can have a dramatic influence on alkylperoxo O-O bond lengths and the barrier to alkylperoxo O-O bond cleavage. Herein, we examine the dioxygen reactivity of a new MnII complex containing a more electron-rich, less sterically demanding NAr ligand scaffold, and compare it with previously reported MnII complexes. Dioxygen binding is shown to be reversible with complexes containing the more electron-rich metal ions. The kinetic barrier to O2 binding and peroxo O-O bond cleavage is shown to correlate with redox potentials, as well as the steric properties of the supporting NAr ligands. The reaction landscape for the dioxygen chemistry of the more electron-rich complexes is shown to be relatively flat. A total of four intermediates, including a superoxo and peroxo species, are observed with the most electron-rich complex. Two new intermediates are shown to form following the peroxo, which are capable of cleaving strong X-H bonds. In the absence of a sacrificial H atom donor, solvent, or ligand, serves as a source of H atoms. With TEMPOH as sacrificial H atom donor, a deuterium isotope effect is observed (kH/kD = 3.5), implicating a hydrogen atom transfer (HAT) mechanism. With 1,4-cyclohexadiene, 0.5 equiv of benzene is produced prior to the formation of an EPR detected MnIIIMnIV bimetallic species, and 0.5 equiv after its formation.

Solvent and Steric Influences on Rotational Dynamics in Porphyrinic Metal–Organic Frameworks with Mechanically Interlocked Pillars

Zinc(II) metal–organic framework (MOF) materials were prepared using a porphyrin-based tetracarboxylate linker and pyridine-terminated [2]rotaxane linkers as pillars. Two pillaring rotaxanes (R = H...

Synthesis of Chiral Bifunctional NHC Ligands and Survey of Their Utilities in Asymmetric Gold Catalysis.

The synthesis and characterization of the chiral bifunctional NHC ligands based on the imidazo[1,5-a]pyridine (ImPy) scaffold are described. These ligands possess a fluxional biaryl axis and a chiral center. The configurational stability of the biaryl axis in their gold(I) complexes is investigated. The application of these axially chiral ImPy-based AuCl complexes in a series of gold catalysis is explored, and varying degrees of asymmetric induction are observed. In most cases, the ligand (aS,R)-L8-H with its cyclohexyl group pointing to the reaction site and hence exerting asymmetric steric influence is more effective in asymmetric induction.

The steric influence of extra-framework cations on framework flexibility: an LTA case study

Abstract The theoretical extent of framework flexibility of Zeolite A (LTA) in response to the steric and geometric effects of different Si/Al compositions and extra-framework cation content has been explored using GASP software. Flexibility windows and compression mechanisms for siliceous LTA and aluminosilicate Na-LTA, Ca-LTA and K-LTA have been modelled. As expected, relatively small cations in the zeolite pores have little effect on the range of flexibility observed. Aluminosilicate LTA, Na-LTA and Ca-LTA frameworks exhibit identical flexibility windows and these frameworks also follow the same compression mechanisms. The introduction of larger K+ ions, however, results in greater steric hindrance. This restricts the flexibility of the framework and alters the compression mechanism to accommodate these larger cations. It is shown that the limits of the flexibility window of Zeolite A are dependent on framework aluminium content and extra-framework cation size.

A CuAAC Click Approach for the Introduction of Bidentate Metal Complexes to a Sulfanilamide-Derived Antibiotic Fragment.

A simple "click-chemistry" approach was employed in order to functionalize the known antibiotic fragment sulfanilamide with a bidentate pyridyl-triazole pocket, which allowed for the synthesis of ruthenium(II) and rhenium(I) carbonyl chloride complexes. Six new complexes were prepared and comprehensively characterized, including five single crystal X-ray structures, photophysical characterization, and testing for antimicrobial activity. Interestingly, functionalization of the pyridine ring with an ortho-hydroxymethyl group resulted in a greater than 100-fold increase in the rate of ligand release in a dimethylsulfoxide solution. Subsequent studies indicated this process could be further accelerated by irradiation with 265 nm light. Structural characterization of four of the complexes indicates that this is the result of a lengthening and weakening of the Re-NPyridine bond (average (Ltri) = 2.19 Å vs LtriOH = 2.25 Å) due to the steric influence of the hydroxymethyl group. The organometallic rhenium(I) pyridyl-triazole functionality maintains its characteristic fluorescent properties despite the presence of the sulfonamide moiety. Two of the compounds showed modest antimicrobial activity against methicillin-resistant Staphylococcus aureus, whereas the structurally similar sulfamethoxazole alone showed no activity under the same conditions.

Destroy the inherent symmetry of vanadium-based inorganic cluster through chiral organic ligand: Synthesis and characterization of a polyoxovanadate-derived amino acid ester hybrid

A hexavanadate-based inorganic–organic hybrid with chiral ligand, (Bu4N)2[V6O19{(OCH2)3CCH2OOCCH2CH2CONHCH(COOC(CH3)3)CH2CH(CH3)2}2] (V6-Leu), was successfully constructed by remote functionalization with chiral amino acid ester through convenient and mild organic reactions. The obtained inorganic–organic derivative was structurally confirmed by FT–IR, NMR, and ESI–MS. The crystal of such complex hybrid was fortunately obtained as well as tested by single crystal XRD. Owing to the steric influence from the chiral ligand, the symmetry of the parent structure was destroyed. In addition, hydrogen bonds were found in the crystal structure, and the donors as well as acceptors of the hydrogen bonds were just in the same molecule but different sides, which also arranged the hybrids into a fascinating chain-like polymer.

Theoretical Investigation of Steric Effect Influence on Reactivity of Substituted Butadienes with Bromocyclobutenone.

The Diels-Alder reaction (DA) between various mono- and disubstituted 1,3-butadiene (Dn-1 to Dn-10) and 2-bromocyclobutenone (DPh) was carried out in gas phase using density functional theory (DFT) at the M06-2X/6-31+g** level. The reaction was found to proceed through a concerted asynchronous transition state. Further, the asynchronous and early nature of the transition state was clearly pinpointed with the frontier molecular orbital (FMO) and bond order index (BOI) analyses. The intermolecular hydrogen bonding interaction along with steric encumbrance in the transition state were found to be the predominant factors in controlling the reactivity of the dienes. Among the investigated dienes, Dn-6 was found to be the most reactive diene which is attributed to its low activation barrier due to the presence of strong intermolecular H-bonding interactions. These factors were further supported by quantum mechanical calculations using global descriptor indexes, natural bond orbital analysis, and quantum theory of atoms in molecules analysis. These theoretical results were found to be in good agreement with the previous experimental findings.

Substituent effects in the zinc(II) coordination chemistry of isomeric pyridylpyrazole ligands

Pyrazoles with unsymmetric substitution are useful ligands in coordination chemistry, but are under-developed due to synthetic challenges in accessing the pure isomers. We have prepared four new structurally related N-(2-pyridyl)-3,5-dialkylpyrazole ligands, L1–L4, and probed their coordination chemistry in the crystalline phase and in solution to elucidate a relationship between steric influence of the alkyl substituents, the stability of the subsequent metal complexes, and their crystal packing influences. We find that L1 and L2, bearing linear or branched alkyl substituents, show similar stabilities and crystal packing motifs featuring π···π and C-H···Cl interactions in the crystalline complexes 1 and 2, respectively. The cyclohexyl-fused species L3 and L4 vary both in the solution stability of complexes 3 and 4, respectively, and in their crystal packing. Complex [ZnCl2(L3)] (3) is a mononuclear complex similar to 1 and 2, albeit with π···π interactions disallowed by the bulk of the cyclohexyl ring. Reaction of isomeric L4 with ZnCl2 gives two polymorphic complexes, 4α and 4β, of the form [Zn2Cl2(μ2-Cl)2(L4)2], varying only in their long-range packing modes. These results show the importance of understanding the steric influences in substituted pyridylpyrazoles, which determine both stability in solution and speciation in the crystalline phase.

Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-tert-butylbenzoic acid with isoniazid and its derivatized forms.

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4-tert-butylbenzoic acid via a one-pot covalent and supramolecular synthesis, namely 4-tert-butylbenzoic acid-isoniazid, C6H7N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(propan-2-ylidene)isonicotinohydrazide, C9H11N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(butan-2-ylidene)isonicotinohydrazide, C10H13N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(diphenylmethylidene)isonicotinohydrazide, C19H15N3O·C11H14O2, and 4-tert-butylbenzoic acid-N'-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C12H17N3O2·C11H14O2. The co-former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan-2-one, butan-2-one, benzophenone and 3-hydroxy-3-methylbutan-2-one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of 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.

Mono- and bimetallic amidinate samarium complexes - synthesis, structure, and hydroamination catalysis.

In order to investigate the difference between mono- and bimetallic systems in the catalytic hydroamination/cyclization reaction two mono- and bimetallic amidinate samarium catalysts, featuring comparable coordination environments, were synthesized. Both systems comprise two {N(SiMe3)2}- leaving groups to minimize the steric influence of the corresponding amidinate ligand. The bimetallic system is based on a bis(amidinate) 4,6-dibenzofuran derivative, while N,N'-bis(2,6-diisopropylphenyl)benzamidinate was employed as ligand for the monometallic catalyst. For the hydroamination/cyclization reaction five different substrates were investigated. Additionally, kinetic studies were carried out to gain deeper understanding of the mechanism.

Pd(4-R3Si-IPr)(allyl)Cl], a Family of Silyl-Substituted Pd–NHC Complexes: Catalytic Systems for the Buchwald–Hartwig Amination

A family of Pd–IPr complexes (1Pd–6Pd) featuring electropositive and bulky R3Si substituents at the 4-position of the NHC ring was prepared and fully characterized. The catalytic performance of 1Pd (R3Si = SiMe3) and 3Pd (R3Si = Si(allyl)Me2) in the Buchwald–Hartwig amination was excellent, notably outperforming those of other previously reported catalytic systems by requiring shorter reaction times, lower catalyst loadings, and milder reaction conditions. Furthermore, a systematic evaluation of both the electronic and steric influences of the 4-R3Si-IPr ligand on the overall catalytic performance of 1Pd–6Pd revealed that electronic rather than steric factors play a dominant role.

Halogen Bond Asymmetry in Solution.

Halogen bonding is the noncovalent interaction of halogen atoms in which they act as electron acceptors. Whereas three-center hydrogen bond complexes, [D···H···D]+ where D is an electron donor, exist in solution as rapidly equilibrating asymmetric species, the analogous halogen bonds, [D···X···D]+, have been observed so far only to adopt static and symmetric geometries. Herein, we investigate whether halogen bond asymmetry, i.e., a [D–X···D]+ bond geometry, in which one of the D–X bonds is shorter and stronger, could be induced by modulation of electronic or steric factors. We have also attempted to convert a static three-center halogen bond complex into a mixture of rapidly exchanging asymmetric isomers, [D···X–D]+ ⇄ [D–X···D]+, corresponding to the preferred form of the analogous hydrogen bonded complexes. Using 15N NMR, IPE NMR, and DFT, we prove that a static, asymmetric geometry, [D–X···D]+, is obtained upon desymmetrization of the electron density of a complex. We demonstrate computationally that conversion into a dynamic mixture of asymmetric geometries, [D···X–D]+ ⇄ [D–X···D]+, is achievable upon increasing the donor–donor distance. However, due to the high energetic gain upon formation of the three-center-four-electron halogen bond, the assessed complex strongly prefers to form a dimer with two static and symmetric three-center halogen bonds over a dynamic and asymmetric halogen bonded form. Our observations indicate a vastly different preference in the secondary bonding of H+ and X+. Understanding the consequences of electronic and steric influences on the strength and geometry of the three-center halogen bond provides useful knowledge on chemical bonding and for the development of improved halonium transfer agents.

Formation and Properties of the Trichloroberyllate Ion.

The activation of C-Cl bonds in dichloromethane and chloroform was observed by BeCl2 in the presence of PMe3 and PCy3. This leads to the formation of [Me3PCH2Cl]Cl and [Cy3PCHCl2][BeCl3]. The latter compound is the first example of a tricoordinated beryllium species with nonbulky ligands and proof of the existence and stability of the long-predicted [BeCl3]- ion. In analogy to the isoelectronic BCl3, the trichloroberyllate anion exhibits Lewis acidic behavior toward electron-pair donors and was probed for the electronic and steric influence of the Lewis base. [BeCl3]- can also act as a chloride ion donor or acceptor, leading to the formation of neutral phosphane adducts to BeCl2 and [BeCl4]2-. The existing equilibria between these species were investigated and showed high chloride mobility.

A non-MPD-type reverse osmosis membrane with enhanced permselectivity for brackish water desalination

A new sulfonated diamine monomer, namely 3,3′-(ethane-1,2-diylbis(azanediyl))bis(2,6-dimethylbenzenesulfonic acid) (EDADMBSA), was designed and synthesized in order to fabricate a novel thin-film composite (TFC) reverse osmosis (RO) membrane by using the interfacial polymerization (IP) technique with trimesoyl chloride (TMC). In particular, EDADMBSA was employed as the sole reactant in the aqueous phase during the IP process, instead of the conventional m-phenylene diamine (MPD). Due to the presence of two methyl groups next to a phenylamino group that could exert a strong steric hindrance influence, the rotation of the polyamide main chain was significantly enforced, as clearly illustrated by a molecular dynamics simulation. In this manner, sufficient free volumes were generated in the polymer matrix, allowing for a lower water penetration resistance. The optimal pure water permeability (PWP) attained with this EDADMBSA/TMC membrane was as high as 1.9 ± 0.2 L m−2 h−1 bar−1, which is 2.6–2.7 times greater than that of a self-made MPD/TMC membrane under the same test conditions. Furthermore, the unique methyl substituents could also serve as void occupiers, allowing the TFC membrane to retain a reasonably high water-solute selectivity. Compared to commercial BW30FR (Dow Chemical), the novel membrane displayed a superior ability to reject all the ions in a simulated desalination test, revealing its promising potential as a separation medium for brackish water desalination.

Cobalt Complexes as an Emerging Class of Catalysts for Homogeneous Hydrogenations.

Catalytic hydrogenation using molecular hydrogen represents a green and practical approach for reductions of all kinds of organic chemicals. Traditionally, in the majority of these processes the presence of transition metal catalysts is required. In this regard, noble-metal-based catalysts have largely been implemented, such as the application of iridium, palladium, rhodium, ruthenium, and others. Recently, the employment of earth-abundant 3d metals has emerged to replace the utilization of scarce noble metals because of their availability, lower cost, and often reduced toxicity. In this respect, several cobalt complexes, in the form of either molecularly well-defined or in situ-formed complexes, are receiving increasing attention from the scientific community. Importantly, the stability and reactivity of the complexes have greatly been supported by multidentate ligands under steric and/or electronic influences. For instance, tridentate or tetradentate phosphine ligands indirectly tune the reactivity of the metal center to accelerate the overall process, whereas direct participation of the ligand in pincer-type complexes through ligand-metal cooperation regulates the elementary steps in the catalytic cycle. In this Account, we emphasize specifically the advancements in cobalt-catalyzed hydrogenations using molecular hydrogen accomplished in our group. A variety of substrate classes ranging from simple molecules (e.g., carbon dioxide) to complex compounds were explored under the mild and efficient catalytic conditions. Notable examples include the reduction of carbon dioxide to afford either formates using a Co(BF4)2·6H2O/Tetraphos catalyst system or methanol employing a Co(acac)3/Triphos complex in the presence of HNTf2. As interesting examples of the synthesis of fine chemicals, cobalt-promoted hydrogenations of nitriles to primary amines and reductive alkylations of indoles using carboxylic acids as alkylating agents are highlighted. Moreover, highly selective hydrogenations of N-heteroarenes under additive-free conditions were possible by the application of specific cobalt complexes. More recently, a set of carboxylic esters could be hydrogenated to the corresponding alcohols with high efficiency by the use of a well-defined cobalt-PNP pincer catalyst. In particular, the decent reactivity of cobalt catalysts enabled high selectivity and functional group tolerance to be achieved. Throughout our studies, it was found that the pairing of a suitable cobalt precursor and an appropriate tridentate or tetradentate phosphine ligand plays a crucial role harnessing the desired reactivity, while other monodentate and bidentate phosphine ligands showed no reactivity in these investigations. Our developments could provide supervisory information for the future exploration of cobalt-catalyzed hydrogenation reactions and other types of reactions involving cobalt catalysis. Furthermore, relevant contributions from other groups, remaining challenges, and future perspectives in this research area are also presented.

Solid‐state and Computational Study of “Venus fly‐trap” Geometric Parameters for 1,5‐Cyclooctadiene in PdII and PtII β‐Enaminonato Complexes

The cod ligand (cis,cis‐1,5‐cyclooctadiene) can be superficially considered to mimic similarities in spatial behavior of a leaf of the Venus fly‐trap (Dionaea muscipula). Thus, the synthesis of an unsymmetrical bidentate trans ligand (N,O‐donor atoms) based on the β‐enaminonate backbone is introduced to evaluate the electronic and steric influence on the structural behavior of the cod ligand when coordinated to a square planar transition metal. A range of platinum(II) / palladium(II) complexes of the type [M(cod)(N,O‐Bid)]A (M = PtII, PdII; β‐enaminonato ligand (N,O‐Bid) = NH‐acac, NMe‐acac, NPh‐acac; A = BF4–, PF6–) is reported. The complexes were fully characterized, including by detailed X‐ray structural investigations. Theoretical calculations on the [M(cod)(N,O‐Bid)]+ complexes for the complete nickel triad are also described and the structural behavior of the cod ligand critically evaluated. The influence of the variation of the β‐enaminonato ligands on the coordination arrangement of the cod was investigated and found that no significant changes to the M–C and C=C bond lengths were observed. The Venus fly‐trap jaw angle (ψ), however, varies by ca. 8° and the twist angle (τ) by ca. 10°, whereas the cod bite angle (χ), as well as the β‐enaminonato ligand bite angle (N–M–O; θ) both remain virtually constant. Calculated spectroscopic tendencies within the Ni‐triad are also included.

Apurinic/apyrimidinic (AP) endonuclease 1 processing of AP sites with 5' mismatches.

Despite the DNA duplex being central to biological functions, many intricacies of this molecule, including the dynamic nature of mismatched base pairing, are still unknown. The unique conformations adopted by DNA mismatches can provide insight into the forces at play between nucleotides. Moreover, DNA-binding proteins apply their own individualized steric and electrochemical influences on the nucleotides that they interact with, further altering base-pairing conformations. Here, seven X-ray crystallographic structures of the human nuclease apurinic/apyrimidinic (AP) endonuclease 1 (APE1) in complex with its substrate target flanked by a 5' mismatch are reported. The structures reveal how APE1 influences the conformations of a variety of different mismatched base pairs. Purine-purine mismatches containing a guanine are stabilized by a rotation of the guanine residue about the N-glycosidic bond to utilize the Hoogsteen edge for hydrogen bonding. Interestingly, no rotation of adenine, the other purine, is observed. Mismatches involving both purine and pyrimidine bases adopt wobble conformations to accommodate the mismatch. Pyrimidine-pyrimidine mismatches also wobble; however, the smaller profile of a pyrimidine base results in a gap between the Watson-Crick faces that is reduced by a C1'-C1' compression. These results advance our understanding of mismatched base pairing and the influence of a bound protein.