Quantification of the Strength of π‐Noncovalent Interactions in Molecular Balances using Density Functional Methods

Different molecular balances were designed previously to compare noncovalent interactions. However, some balances are difficult to synthesise and there is a need for developing a computational approach. In this work, we probe noncovalent interactions of π systems using DFT methods to assess their reliability in reproducing experimentally measured conformer populations. Based on our results, the PW6B95D3 functional performed best, followed by M11L and ωB97XD. Additionally, the simulation of the rotation of the hydroxyl group revealed stabilising OH⋯Alkyne and OH⋯Nitrile interactions that are difficult to identify experimentally. These methods were then applied to compare the strengths of sulfur⋯π interactions in molecules which have not been explored experimentally. Compared to the hydroxyl counterpart, the simulation of the thiol group rotation showed that the geometry of the conformer with the two sulfur lone pairs oriented towards the aromatic ring or the double bond is stabilised, suggesting that S(LP)⋯π interactions can be attractive in nature. The ability of sulfur to rearrange its electronic surrounding to form an attractive interaction with π systems, including those with either electron-donating or withdrawing groups, was also confirmed. Overall, the results show a promising future for both qualitative and quantitative assessments of the strengths of noncovalent interactions using selected DFT techniques

Trimethylplatinum(IV) complexes of anionic N/O and O/O donor ligands: synthesis, NMR and fluxional behaviour

Reaction of pentane-2,4-dione, pyridine-2-carboxylic acid or pyridine-2,6-dicarboxylic acid with trimethylplatinum(IV) gives dimeric complexes of general formulae fac-[PtMe₃L]₂, in which the ionised ligand acts in a chelating and a bridging fashion. High-resolution solid-state ¹⁹ ;Pt NMR data shows that the two platinum atoms are equivalent ; the chemical shielding anisotropy and the principal components of the shielding tensor are reported. The complexes are soluble in co-ordinating solvents, yielding monomeric species of general formulae fac-[PtMe₃L(solvent)], which are fluxional. The pyridine adducts, fac-[PtMe₃L(py)] (L = pentane-2,4-dionato or pyridine-2-carboxylato), are also stereochemically non-rigid. The energetics of the dynamic processes have been studied by standard ¹H NMR band shape analysis techniques ; ΔG ‡ (298 K) is in the range 69–86 kJ mol⁻¹. Solid-state ¹³C, and solution-state ¹³C and ¹⁹;Pt NMR data are also reported

Conformational properties of monosubstituted cyclohexane guest molecules constrained within zeolitic host materials. A solid-state NMR investigation

The conformational properties of monosubstituted cyclohexane guest molecules (C6H11X with X = CH3, OH, Cl, Br and I) included within microporous solid host materials (silicalite-I, H-ZSM-5, NH4-mordenite and zeolite NH4-Y) have been elucidated via high-resolution solid-state 13C NMR spectroscopy. For all of the inclusion compounds investigated, the fraction of monosubstituted cyclohexane molecules in the equatorial conformation is similar to that in solution, suggesting that these host materials do not impose any significant constraints upon the conformational properties of the monosubstituted cyclohexane guest molecules. For the monohalogenocyclohexane guest molecules (C6H11X with X = Cl, Br and I), this result is in marked contrast to the situation for the same guest molecules in the thiourea host structure, for which the conformational properties of the guest molecules are substantially different from those of the same molecules in solution. For cyclohexanol (C6H11OH) in H-ZSM-5, some amount of dicyclohexyl ether (C6H11OC6H11) is observed, and is analogous to the proposed production of dimethyl ether in the first stage of methanol-to-gasoline conversion on this zeolite. The comparatively low temperature (ambient temperature) at which this conversion from cyclohexanol to dicyclohexyl ether occurs is noteworthy. In addition to our high-resolution solid-state 13C NMR studies of these materials, 1H MAS and 27AI MAS NMR spectra have also been recorded, and are discussed

Luminescent and Swellable Conjugated Microporous Polymers for Detecting Nitroaromatic Explosives and Removing Harmful Organic Vapors

Four new conjugated microporous polymers (CMPs) were synthesized by a Buchwald–Hartwig (BH) cross-coupling reaction of tri- and tetrafunctionalized precursors to yield materials with tunable surface area and pore size distribution. This approach yielded LPCMP1–4, CMPs with significantly higher Brunauer–Emmett–Teller (BET) surface areas (more than 5 times higher) than other related BH-based CMPs. These CMPs possess not only high BET specific surface areas and high chemical and thermal stabilities, but also exhibit outstanding swellability. To the best of our knowledge, swellable behavior was studied in great detail for CMPs for the first time, with the greatest degree of swelling for methanol reaching 16.5 and 16.3 mL g–1 for LPCMP1 and LPCMP3, respectively. Owing to their excellent swellability, we further studied the adsorption capacity of these CMPs for different toxic organic vapors (including toluene and methanol). LPCMP1 and LPCMP3 adsorbed 124 and 117 mg g–1 toluene, respectively, at saturated vapor pressure. For methanol, the adsorption capacities of LPCMP1 and LPCMP3 were up to 250 and 215 mg g–1, respectively, which are the highest recorded values when compared with published data for CMPs, HCPs, MOFs, and porous carbons. These materials are promising candidates for the removal and elimination of hazardous organic vapors and chemical warfare agents. Moreover, all the polymers show high sensitivity to nitroaromatic explosives. LPCMP2 and LPCMP4 exhibit high selectivity for TNT and may be suitable as new candidates to selectively detect TNT for security or environmental applications

Unearthing the unique stability of thiophosphonium-C-terminal cysteine adducts on peptides and proteins

Herein we report a fundamental discovery on the use of tris(dialkylamino)phosphine reagents for peptide and protein modification. We discovered that C-terminal thiophosphonium species, which are uniquely stable, could be selectively and rapidly generated from their disulfide counterparts. In sharp and direct contrast, internal thiophosphonium species rapidly degrade to dehydroalanine. We demonstrate this remarkable chemoselectivity on a bis-cysteine model peptide, and the formation of a stable C-terminal-thiophosphonium adduct on an antibody fragment, as well as characterise the species in various small molecule/peptide studies

Multi-enzyme catalysed processes using purified and whole-cell biocatalysts towards a 1,3,4-substituted tetrahydroisoquinoline

In this work, two multi-enzyme catalysed processes to access a 1,3,4-substituted tetrahydroisoquinoline (THIQ), using either purified enzymes or lyophilised whole-cell catalysts, are presented. A key focus was the first step in which the reduction of 3-hydroxybenzoic acid (3-OH-BZ) into 3-hydroxybenzaldehyde (3-OH-BA) was catalysed by a carboxylate reductase (CAR) enzyme. Incorporation of the CAR-catalysed step enables substituted benzoic acids as the aromatic components, which can potentially be obtained from renewable resources by microbial cell factories. In this reduction, the implementation of an efficient cofactor regeneration system of both ATP and NADPH was crucial. Two different recycling approaches, either using purified enzymes or lyophilised whole-cells, were established and compared. Both of them showed high conversions of the acid into 3-OH-BA (>80%). However, the whole-cell system showed superior performance because it allowed the combination of the first and second steps into a one-pot cascade with excellent HPLC yields (>99%, enantiomeric excess (ee) ≥ 95%) producing the intermediate 3-hydroxyphenylacetylcarbinol. Moreover, enhanced substrate loads could be achieved compared to the system employing only purified enzymes. The third and fourth steps were performed in a sequential mode to avoid cross-reactivities and the formation of several side products. Thus, (1R,2S)-metaraminol could be formed with high HPLC yields (>90%, isomeric content (ic) ≥ 95%) applying either purified or whole-cell transaminases from Bacillus megaterium (BmTA) or Chromobacterium violaceum (Cv2025). Finally, the cyclisation step was performed using either a purified or lyophilised whole-cell norcoclaurine synthase variant from Thalictrum flavum (ΔTfNCS-A79I), leading to the formation of the target THIQ product with high HPLC yields (>90%, ic > 90%). As many of the educts applied are from renewable resources and a complex product with three chiral centers can be gained by only four highly selective steps, a very step- and atom efficient approach to stereoisomerically pure THIQ is shown

Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water

The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pKa primary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5-9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as β- and γ-peptides, displays poor selectivity. Notably, this discovery enables the highly α-selective protecting-group-free ligation of lysine peptides at neutral pH while leaving the functional ε-amine side chain intact

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV-visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV–visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

An NMR Method for Quantitative Assessment of Intramolecular Hydrogen Bonding; Application to Physiochemical, Environmental, and Biochemical Properties

Article on an NMR method for the quantitative assessment of intramolecular hydrogen bonding and an application to physiochemical, environmental, and biochemical properties