Exploring the Strength of the H‐Bond in Synthetic Models for Heme Proteins: The Importance of the N−H Acidity of the Distal Base

The distal hydrogen bond (H‐bond) in dioxygen‐binding proteins is crucial for the discrimination of O₂ with respect to CO or NO. We report the preparation and characterization of a series of Zn^II porphyrins, with one of three meso‐phenyl rings bearing both an alkyl‐tethered proximal imidazole ligand and a heterocyclic distal H‐bond donor connected by a rigid acetylene spacer. Previously, we had validated the corresponding Co^II complexes as synthetic model systems for dioxygen‐binding heme proteins and demonstrated the structural requirements for proper distal H‐bonding to Co^II‐bound dioxygen. Here, we systematically vary the H‐bond donor ability of the distal heterocycles, as predicted based on pK_a values. The H‐bond in the dioxygen adducts of the Co^II porphyrins was directly measured by Q‐band Davies‐ENDOR spectroscopy. It was shown that the strength of the hyperfine coupling between the dioxygen radical and the distal H‐atom increases with enhanced acidity of the H‐bond donor.     

Probing the Hydrogen Bonding Structure in the Rieske Protein

The use of the far‐infrared spectral range presents a novel approach for analysis of the hydrogen bonding in proteins. Here it is presented for the analysis of Fe? S vibrations (500–200 cm^?1) and of the intra‐ and intermolecular hydrogen bonding signature (300–50 cm^?1) in the Rieske protein from Thermus thermophilus as a function of temperature and pH. Three pH values were adequately chosen in order to study all the possible protonation states of the coordinating histidines. The Fe? S vibrations showed pH‐dependent shifts in the FIR spectra in line with the change of protonation state of the histidines coordinating the [2Fe? 2S] cluster. Measurements of the low‐frequency signals between 300 and 30 K demonstrated the presence of a distinct overall hydrogen bonding network and a more rigid structure for a pH higher than 10. To further support the analysis, the redox‐dependent shifts of the secondary structure were investigated by means of an electrochemically induced FTIR difference spectroscopic approach in the mid infrared. The results confirmed a clear pH dependency and an influence of the immediate environment of the cluster on the secondary structure. The results support the hypothesis that structure‐mediated changes in the environment of iron? sulfur centers play a critical role in regulating enzymatic catalysis. The data point towards the role of the overall internal hydrogen bonding organization for the geometry and the electronic properties of the cluster.     

氢键识别超分子聚合物的新进展

近年来,由于氢键作用对聚合物的热力学性质、微观自组装、结晶及液晶行为的重要影响,氢键识别在超分子聚合物的分子设计与结构控制方面的应用受到广泛关注。本文系统介绍了氢键识别体系的类型与性质,以及分子结构、分子内氢键对氢键识别强度的影响,讨论了羧酸与吡啶间氢键识别体系、与核苷相关的氢键识别体系以及四重氢键识别体系在超分子聚合物中的最新应用,主要介绍了氢键识别超分子聚合物的合成、结构、性质及功能。     

Phenylacetylene: A Hydrogen Bonding Chameleon

Molecules with multiple hydrogen bonding sites offer the opportunity to investigate competitive hydrogen bonding. Such an investigation can become quite interesting, particularly when the molecule of interest has neither lone‐pair electrons nor strongly acidic/basic groups. Phenylacetylene is one such molecule with three hydrogen bonding sites that cannot be ranked into any known hierarchical pattern. Herein we review the structures of several binary complexes of phenylacetylene investigated using infrared optical double‐resonance spectroscopy in combination with high‐level ab initio methods. The diversity of intermolecular structures formed by phenylacetylene with various reagents is remarkable. The nature of intermolecular interaction with various reagents is the result of a subtle balance between various configurations and competition between the electrostatic and dispersion energy terms, while trying to maximize the total interaction strength.     

Molecular Recognition by Hydrogen Bonding in Polyelectrolyte Multilayers

Functional polyanions were prepared by copolymerization of sulfopropyl acrylate and sulfopropyl methacrylate with monomers bearing triaminopyrimidine or barbituric acid functionalities, respectively. Functionalized polyelectrolyte multilayers were assembled from these copolymers by stepwise alternating adsorption with poly(choline methacrylate). These multilayers are suited for molecular recognition of substrates that are complementary to the functional groups incorporated. Thus, multilayers containing triaminopyrimidine moieties selectively bind barbituric acid, and vice versa, when exposed to solutions of the 1:1 complex of barbituric acid and triaminopyrimidine. The molecular recognition process was monitored by UV/Vis spectroscopy, time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and photoelectron spectroscopy (XPS). Remarkably, after successful recognition and binding of the complementary substrates to the multilayers, the stepwise layering could be continued.     

Selectivity of DNA Replication: The Importance of Base-Pair Geometry over Hydrogen Bonding

The polymerase enzyme hardly differentiates between thymine and difluorotoluene nucleotides with respect to the replication selectivity. X-ray structure analysis show the importance of the Watson–Crick geometry for the replication fidelity; base selection is determined by the spatial prerequisite of the substrate pocket and directed protein interactions in the minor groove (schematically shown on the right).     

Iron twin-coronet porphyrins as models of myoglobin and hemoglobin: amphibious electrostatic effects of overhanging hydroxyl groups for successful CO/O2 discrimination

Inspired by the observation of polar interactions between CO and O(2) ligands and the peptide residues at the active site of hemoglobin and myoglobin, we synthesized two kinds of superstructured porphyrins: TCP-IM, which contains a linked imidazole ligand, and TCP-PY, which contains a linked pyridine ligand, and examined the thermodynamic, kinetic, and spectroscopic (UV/Vis, IR, NMR, and resonance Raman) properties of their CO and O(2) complexes. On both sides of each porphyrin plane, bulky binaphthyl bridges form hydrophobic cavities that are suitable for the binding of small molecules. In the proximal site, an imidazole or pyridine residue is covalently fixed and coordinates axially to the central iron atom. In the distal site, two naphtholic hydroxyl groups overhang toward the center above the heme. The CO affinities of TCPs are significantly lower than those of other heme models. In contrast, TCPs have moderate O(2) binding ability. Compared with reported model hemes, the binding selectivity of O(2) over CO in TCP-IM and TCP-PY complexes is greatly improved. The high O(2) selectivity of the TCPs is mainly attributable to a low CO affinity. The comparison of k(on)(CO) values of TCPs with those of unhindered hemes indicates the absence of steric hindrance to the intrinsically linear CO coordination to Fe(II) in TCP-IM and TCP-PY. The abnormally large k(off)(CO) values are responsible for the low CO affinities. In contrast, k(off)(O(2)) of TCP-PY is smaller than those of other pyridine-coordinated model hemes. For the CO adducts of TCPs, unusually low nu(Fe-CO) and unusually high nu(C-O) frequencies are observed. These results can be ascribed to decreased back-bonding from the iron atom to the bound CO. The lone pairs of the oxygen atoms of the hydroxyl groups prevent back-bonding by exertion of a strong negative electrostatic interaction. On the other hand, high nu(Fe-O(2)) frequencies are observed for the O(2) adducts of TCPs. In the resonance Raman (RR) spectrum of oxy-TCP-IM, we observed simultaneous enhancement of the Fe-O(2) and O-O stretching modes. Furthermore, direct evidence for hydrogen bonding between the hydroxyl groups and bound dioxygen was obtained by RR and IR spectroscopy. These spectroscopic data strongly suggest that O(2) and CO binding to TCPs is controlled mainly by the two different electrostatic effects exerted by the overhanging OH groups: destabilization of CO binding by decreasing back-bonding and stabilization of O(2) binding by hydrogen bonding.     

Guest–Host Hydrogen Bonding in Structure H Clathrate Hydrates

Molecular dynamics simulations of the structure H (sH) clathrate of tert‐butylmethylether show the prevalence of ether–water hydrogen bonding (see picture), absent in the neo‐hexane sH clathrate. This affects guest–cage dynamics and host–water dielectric relaxation dynamics. The ¹³C and ¹H NMR relaxation times for both guests are measured, and the differences are explained in terms of guest–host interactions in the two clathrates.

     

HNO‐Binding in Heme Proteins: Effects of Iron Oxidation State,Axial Ligand,and Protein Environment

HNO plays significant roles in many biological processes. Numerous heme proteins bind HNO, an important step for its biological functions. A systematic computational study was performed to provide the first detailed trends and origins of the effects of iron oxidation state, axial ligand, and protein environment on HNO binding. The results show that HNO binds much weaker with ferric porphyrins than corresponding ferrous systems, offering strong thermodynamic driving force for experimentally observed reductive nitrosylation. The axial ligand was found to influence HNO binding through its trans effect and charge donation effect. The protein environment significantly affects the HNO hydrogen bonding structures and properties. The predicted NMR and vibrational data are in excellent agreement with experiment. This broad range of results shall facilitate studies of HNO binding in many heme proteins, models, and related metalloproteins.     

Inhibition of Heme Uptake in Pseudomonas aeruginosa by its Hemophore (HasAp) Bound to Synthetic Metal Complexes

The heme acquisition system A protein secreted by Pseudomonas aeruginosa (HasA_p) can capture several synthetic metal complexes other than heme. The crystal structures of HasA_p harboring synthetic metal complexes revealed only small perturbation of the overall HasA_p structure. An inhibitory effect upon heme acquisition by HasA_p bearing synthetic metal complexes was examined by monitoring the growth of Pseudomonas aeruginosa PAO1. HasA_p bound to iron–phthalocyanine inhibits heme acquisition in the presence of heme‐bound HasA_p as an iron source.     

Hydrogen Bonding versus Halogen Bonding: Spectroscopic Investigation of Gas-Phase Complexes Involving Bromide and Chloromethanes

Hydrogen bonding and halogen bonding are important non-covalent interactions that are known to occur in large molecular systems, such as in proteins and crystal structures. Although these interactions are important on a large scale, studying hydrogen and halogen bonding in small, gas-phase chemical species allows for the binding strengths to be determined and compared at a fundamental level. In this study, anion photoelectron spectra are presented for the gas-phase complexes involving bromide and the four chloromethanes, CH₃Cl, CH₂Cl₂, CHCl₃, and CCl₄. The stabilisation energy and electron binding energy associated with each complex are determined experimentally, and the spectra are rationalised by high-level CCSD(T) calculations to determine the non-covalent interactions binding the complexes. These calculations involve nucleophilic bromide and electrophilic bromine interactions with chloromethanes, where the binding motifs, dissociation energies and vertical detachment energies are compared in terms of hydrogen bonding and halogen bonding.     

The Hydrogen Bond and Beyond: Perspectives for Rotational Investigations of Non-Covalent Interactions

In the last decade, experiment and theory have expanded our vision of non-covalent interactions (NCIs), shifting the focus from the conventional hydrogen bond to new bridging interactions involving a variety of weak donor/acceptor partners. Whereas most experimental data originate from condensed phases, the introduction of broadband (chirped-pulse) microwave fast-passage techniques has revolutionized the field of rotational spectroscopy, offering unexplored avenues for high-resolution studies in the gas phase. We present an outlook of hot topics for rotational investigations on isolated intermolecular clusters generated in supersonic jet expansions. Rotational spectra offer very detailed structural data, easily discriminating the isomeric or isotopic composition and effectively cancelling any solvent, crystal, or matrix bias. The direct comparison with quantum mechanical predictions provides insight into the origin of the inter- and intramolecular interactions with much greater precision than any other spectroscopic technique, simultaneously serving as test-bed for fine-tuning of theoretical methods. We present recent examples of rotational investigations around three topics: oligomer formation, chiral recognition, and identification of halogen, chalcogen, pnicogen, or tetrel bonds. The selected examples illustrate the benefits of rotational spectroscopy for the structural and energetic assessment of inter-/intramolecular interactions, which may help to move from fundamental research to applications in supramolecular chemistry and crystal engineering.     

The Six Isomers of the Cyclohexanol Dimer: A Delicate Test for Dispersion Models

The cyclohexanol homodimer acts as a delicate test model of the role of dispersion forces in intermolecular association. Whereas phenol produces a single dimer, the suppression of π interactions and the larger conformational flexibility in cyclohexanol results in multiple isomerism, with six competing dimers of the free molecule being observed in a supersonic jet expansion. Rotational spectroscopy reveals accurate structural data, specifically the formation of homo‐ and heterochiral diastereoisomers and the presence of both equatorial and axial forms in the dimers. Four dispersion‐corrected density‐functional molecular orbital calculations were tested against the experiment, with B3LYP‐D3(BJ) offering good structural reproducibility with an Alrich's triple‐ζ basis set. However, the prediction of the dimer energetics is largely model‐dependent, thus offering a testbed for the validation of dispersion‐corrected computational models.     

Hydrogen Bonding in Liquid Water and in the Hydration Shell of Salts

A near‐IR spectral study on pure water and aqueous salt solutions is used to investigate stoichiometric concentrations of different types of hydrogen‐bonded water species in liquid water and in water comprising the hydration shell of salts. Analysis of the thermodynamics of hydrogen‐bond formation signifies that hydrogen‐bond making and breaking processes are dominated by enthalpy with non‐negligible heat capacity effects, as revealed by the temperature dependence of standard molar enthalpies of hydrogen‐bond formation and from analysis of the linear enthalpy–entropy compensation effects. A generalized method is proposed for the simultaneous calculation of the spectrum of water in the hydration shell and hydration number of solutes. Resolved spectra of water in the hydration shell of different salts clearly differentiate hydrogen bonding of water in the hydration shell around cations and anions. A comparison of resolved liquid water spectra and resolved hydration‐shell spectra of ions highlights that the ordering of absorption frequencies of different kinds of hydrogen‐bonded water species is also preserved in the bound state with significant changes in band position, band width, and band intensity because of the polarization of water molecules in the vicinity of ions.