Halogen Bonding versus Hydrogen Bonding: A Molecular Orbital Perspective

We have carried out extensive computational analyses of the structure and bonding mechanism in trihalides DX⋅⋅⋅A⁻ and the analogous hydrogen-bonded complexes DH⋅⋅⋅A⁻ (D, X, A=F, Cl, Br, I) using relativistic density functional theory (DFT) at zeroth-order regular approximation ZORA-BP86/TZ2P. One purpose was to obtain a set of consistent data from which reliable trends in structure and stability can be inferred over a large range of systems. The main objective was to achieve a detailed understanding of the nature of halogen bonds, how they resemble, and also how they differ from, the better understood hydrogen bonds. Thus, we present an accurate physical model of the halogen bond based on quantitative Kohn–Sham molecular orbital (MO) theory, energy decomposition analyses (EDA) and Voronoi deformation density (VDD) analyses of the charge distribution. It appears that the halogen bond in DX⋅⋅⋅A⁻ arises not only from classical electrostatic attraction but also receives substantial stabilization from HOMO–LUMO interactions between the lone pair of A⁻ and the σ* orbital of D–X.     

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.     

Imaging of Single Molecular Behaviors Under Bifurcated Three-Centered Hydrogen Bonding

The mechanism for interaction and bonding of single guest molecules with active sites fundamentally determines the sorption and subsequent catalytic processes occurring in host zeolitic frameworks. However, no real-space studies on these significant issues have been reported thus far, since atomically visualizing guest molecules and recognizing single Al T-sites in zeolites remain challenging. Here, we atomically resolved single thiophene probes interacting with acid T-sites in the ZSM-5 framework to study the bonding behaviors between them. The synergy of bifurcated three-centered hydrogen bonds and van der Waals interactions can “freeze” the near-horizontal thiophene and make it stable enough to be imaged. By combining the imaging results with simulations, direct atomic observations enabled us to precisely locate the single Al T-sites in individual straight channels. Then, we statistically found that the thiophene bonding probability of the T11 site is 15 times higher than that of the T6 site. For different acid T-sites, the variation in the interaction synergy changes the inner angle of the host–guest O−H⋅⋅⋅S hydrogen bond, thereby affecting the stability of the near-horizontal thiophene and leading to considerable bonding inhomogeneities.     

芳杂环类多重氢键分子钳人工受体研究新进展

氢键是分子识别的重要推动力之一.综述了芳杂环类多重氢键分子钳人工受体研究进展.     

甘油水溶液氢键特性的分子动力学模拟

为了研究低温保护剂溶液的结构和物理化学特性, 以甘油为保护剂, 采用分子动力学方法, 对不同浓度的甘油和水的二元体系进行了模拟. 得到了不同浓度的甘油水溶液在2 ns内的分子动力学运动轨迹, 通过对后1 ns内运动轨迹的分析, 得到了各个原子对的径向分布函数和甘油分子的构型分布. 根据氢键的图形定义, 分析了氢键的结构和动力学特性. 计算了不同浓度下体系中平均每个原子(O和H)和分子(甘油和水)参与氢键个数的百分比分布及其平均值. 同时还计算了所有氢键、水分子之间的氢键以及甘油与水分子之间的氢键的生存周期.     

Predicting the Limit of Intramolecular Hydrogen Bonding with Classical Molecular Dynamics

The energetics of intramolecular recognition processes are governed by the balance of pre‐organization and flexibility, which is often difficult to measure and hard to predict. Using classical MD simulations, we predict and quantify the effective strength of intramolecular hydrogen bonds between donor and acceptor sites separated by a variable alkyl linker in several solvents and crowded solutions. The balance of entropic and enthalpic contributions poses a solvent‐dependent limit to the occurrence of intramolecular H‐bonding. Still, free energies show a constant offset among different solvents with, for example, a 13 kJ mol^?1 difference between water and chloroform. Molecular crowding shows little effect on the thermodynamic equilibrium, but induces variations on the H‐bond kinetics. The results are in quantitative agreement with experiments in chloroform and showcase a general strategy to investigate molecular interactions in different environments, extending the limits of current experiments towards the prospective prediction of H‐bond interactions in a variety of contexts.     

Endohedral Hydrogen Bonding Templates the Formation of a Highly Strained Covalent Organic Cage Compound**

A highly strained covalent organic cage compound was synthesized from hexahydroxy tribenzotriquinacene (TBTQ) and a meta-terphenyl-based diboronic acid with an additional benzoic acid substituent in 2’-position. Usually, a 120° bite angle in the unsubstituted ditopic linker favors the formation of a [4+6] cage assembly. Here, the introduction of the benzoic acid group is shown to lead to a perfectly preorganized circular hydrogen-bonding array in the cavity of a trigonal-bipyramidal [2+3] cage, which energetically overcompensates the additional strain energy caused by the larger mismatch in bite angles for the smaller assembly. The strained cage compound was analyzed by mass spectrometry and ¹H, ¹³C and DOSY NMR spectroscopy. DFT calculations revealed the energetic contribution of the hydrogen-bonding template to the cage stability. Furthermore, molecular dynamics simulations on early intermediates indicate an additional kinetic effect, as hydrogen bonding also preorganizes and rigidifies small oligomers to facilitate the exclusive formation of smaller and more strained macrocycles and cages.     

Intermolecular Hydrogen Bonding Modulates O‐H Photodissociation in Molecular Aggregates of a Catechol Derivative

The catechol functional group plays a major role in the chemistry of a wide variety of molecules important in biology and technology. In eumelanin, intermolecular hydrogen bonding between these functional groups is thought to contribute to UV photoprotective and radical buffering properties, but the mechanisms are poorly understood. Here, aggregates of 4‐t‐butylcatechol are used as model systems to study how intermolecular hydrogen bonding influences photochemical pathways that may occur in eumelanin. Ultrafast UV‐visible and mid‐IR transient absorption measurements are used to identify the photochemical processes of 4‐t‐butylcatechol monomers and their hydrogen‐bonded aggregates in cyclohexane solution. Monomer photoexcitation results in hydrogen atom ejection to the solvent via homolytic O‐H bond dissociation with a time constant of 12 ps, producing a neutral semiquinone radical with a lifetime greater than 1 ns. In contrast, intermolecular hydrogen bonding interactions within aggregates retard O‐H bond photodissociation by over an order of magnitude in time. Excited state structural relaxation is proposed to slow O‐H dissociation, allowing internal conversion to the ground state to occur in hundreds of picoseconds in competition with this channel. The semiquinone radicals formed in the aggregates exhibit spectral broadening of both their electronic and vibrational transitions.     

Hydrogen Bonding Interactions of Radicals

Hydrogen bonding interactions of organic radicals are systematically studied using diverse ab initio and density functional theory (DFT) methods. It is found that open-shell hydrogen bonds with radical proton donors are more difficult to model than those with radical proton acceptors. The DFT methods perform significantly worse than the unrestricted second order Möller-Plesset perturbation (UMP2) method in both geometry optimization and interaction energy calculations for the open-shell hydrogen bonds. The UB3LYP method seriously underestimates the donor-acceptor distances and overestimates interaction energies for the open-shell hydrogen bonds with radical proton donors. Nevertheless, use of the UBH&HLYP functional to study the open-shell hydrogen bonds is still acceptable. Furthermore, it is necessary to use sufficiently flexible basis sets, such as 6-311++G(2df,2p), to get reliable interaction energies for the open-shell hydrogen bonds. The open-shell proton donors are stronger Lewis acids than the corresponding closed-shell proton donors. The open-shell proton acceptors are weaker Lewis bases than the corresponding closed-shell proton acceptors.     

氢键能量分划方法

介绍几种氢键能量分划方法以及它们的优缺点,并结合氢键体系的研究现状讨论理论方法在实际体系中的应用。     

Intramolecular Hydrogen Bonding Enables a Zwitterionic Mechanism for Macrocyclic Peptide Formation: Computational Mechanistic Studies of CyClick Chemistry

Macrocyclic peptides have become increasingly important in the pharmaceutical industry. We present a detailed computational investigation of the reaction mechanism of the recently developed “CyClick” chemistry to selectively form imidazolidinone cyclic peptides from linear peptide aldehydes, without using catalysts or directing groups (Angew. Chem. Int. Ed. 2019 , 58, 19073–19080). We conducted computational mechanistic to investigate the effects of intramolecular hydrogen bonds (IMHBs) in promoting a kinetically facile zwitterionic mechanism in “CyClick” of pentapeptide aldehyde AFGPA. Our DFT calculations highlighted the importance of IMHB in pre-organization of the resting state, stabilization of the zwitterion intermediate, and the control of the product stereoselectivity. Furthermore, we have also identified that the low ring strain energy promotes the “CyClick” of hexapeptide aldehyde AAGPFA to form a thermodynamically more stable 15+5 imidazolidinone cyclic peptide product. In contrast, large ring strain energy suppresses “CyClick” reactivity of tetra peptide aldehyde AFPA from forming the 9+5 imidazolidinone cyclic peptide product.     

Supramolecular Formation via Hydrogen Bonding in Copper and Nickel Complexes with 2-Hydroxynicotinic Acid

Two complexes,Cu(HnicO)2 1 and Ni(HnicO)2(H2O)2 2 (H2nicO=2-hydroxy-nicolinic acid),were synthesized by hydrothermal reactions and structurally characterized. Complex 1 crystallizes in monoclinic,space group P21/n,with a=8.314(7),b=6.275(4),c=11.283(7),β =98.32(3)°,V=582.5(7)3,Z=2,Mr=339.74,Dc=1.937 g/cm3,F(000)=342,μ=1.908 mm-1,S =1.097,the final R=0.0284 and wR=0.0781 for 1177 observed reflections with I > 2σ(I). Complex 2 crystallizes in monoclinic,space group P21/c,with a=7.438(5),b=12.22(1),c=7.537(5),β=100.07(3)°,V=674.3(8)3,Z=2,Mr=370.95,Dc=1.827 g/cm3,F(000)=380,μ =1.487 mm-1,S=1.041,the final R=0.0335 and wR=0.0779 for 1202 observed reflections with I > 2σ(I). There are extended 3D framework structures in complexes 1 and 2 due to the N–H…O and C–H…O hydrogen bonds. The copper atom in 1 has square planar coordination,while the nickel atom in 2 adopts octahedral coordination geometry. The TG curve shows that complex 2 is stable in solid state to 150 ℃.     

Heteroatom Effects on Electronic Excited State Hydrogen Bonding of Fluorenone‐Based Molecular Materials

In this work, the geometry optimizations in the ground state and electronic excitation energies and corresponding oscillation strengths of the low‐lying electronically excited states for the isolated fluorenone (FN) and FN‐based molecular monomers, the relatively hydrogen‐bonded dimers, and doubly hydrogen‐bonded trimers, are calculated by the density functional theory and time‐dependent density functional theory methods, respectively. We find the intermolecular hydrogen bond CO···H O is strengthened in some of the electronically excited states of the hydrogen‐bonded dimers and doubly hydrogen‐bonded trimers, because the excitation energy in a related excited state decrease and electronic spectral redshift are induced. Similarly, the hydrogen bond CO···H O is weakened in other excited states. On this basis, owing to the important difference of electronegativity, heteroatoms S, Se, and Te that substitute for the O atom in the carbonyl group of the FN molecule have a significant effect on the strength of the hydrogen bond and the spectral shift. It is observed that the hydrogen bond CTe···H O is too weak to be formed. When the CS and CSe substitute for CO, the strength of the hydrogen bonds and electronic spectra frequency shift are significantly changed in the electronic excited state due to the electron transition type transformation from the ππ* feature to σπ* feature. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:153–162, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21075     

Molecular Recognition of Nucleic Acid Bases in Water by Hydrogen Bonding of Poly(vinyldiaminotriazine)

Poly(2-vinyl-4,6-diamino-1,3,5-triazine) efficiently binds nucleic acid bases and nucleosides in water by using complementary hydrogen bonding. The binding activity decreases in the order: U, T > A C, G. The corresponding monomer shows virtually no activity, indicating a predominant role of polymer effect for the molecular recognition in water.     

槲皮素与腺嘌呤氢键作用的最佳位点

本文优化得到了16个由槲皮素与腺嘌呤形成的氢键复合物的稳定结构,并计算了它们的结合能.研究发现,在气相和水相中,槲皮素均通过qu1位点与腺嘌呤作用形成稳定的氢键复合物.比较了腺嘌呤与槲皮素形成的氢键复合物、腺嘌呤与胸腺嘧啶形成的Watson-Crick碱基对的相对稳定性.在气相条件下Watson-Crick碱基对更稳定,在水相条件下腺嘌呤与槲皮素形成的氢键复合物更稳定,说明水相条件下腺嘌呤与槲皮素之间的相互作用强于与胸腺嘧啶之间的相互作用.基于标准反应Gibbs自由能变的计算结果估算了水相条件下腺嘌呤与槲皮素形成的氢键复合物和Watson-Crick碱基对的相对平衡浓度.     

Hydrogen Bonding as a Supramolecular Tool for Robust OFET Devices

In the present study, we demonstrated the effect of hydrogen bonding in the semiconducting behaviour of a small molecule used in organic field-effect transistors (OFETs). For this study, the highly soluble dumbbell-shaped molecule, Boc-TATDPP based on a Boc-protected thiophene-diketopyrrolopyrrole (DPP) and triazatruxene (TAT) moieties was used. The two Boc groups of the molecule were removed by annealing at 200 °C, which created a strong hydrogen-bonded network of NH-TATDPP supported by additional π–π stacking. These were characterised by thermogravimetric analysis (TGA), UV/Vis and IR spectroscopy, XRD and high-resolution (HR)-TEM measurements. FETs were fabricated with the semiconducting channel made of Boc-TATDPP and NH-TATDPP separately. It is worth mentioning that the Boc-TATDPP film can be cast from solution and then annealed to get the other systems with NH-TATDPP. More importantly, NH-TATDPP showed significantly higher hole mobilities compared to Boc-TATDPP. Interestingly, the high hole mobility in the case of NH-TATDPP was unaffected upon blending with [6,6]-phenyl-C71-butyric acid methyl ester (PC₇₁BM). Thus, this robust hydrogen-bonded supramolecular network is likely to be useful in designing efficient and stable organic optoelectronic devices.     

Studies on the Conformations and Hydrogen Bonding of ACE Inhibitory Tripeptide VEF by All-atom Molecular Dynamics Simulations and Molecular Docking

Molecular dynamic simulations and molecular docking are performed to study the conformations and hydrogen bonding interactions of ACE inhibitory tripeptide VEF. Intramolecular distance, radius of gyration, solvent-accessible surface, and root-mean-square deviations are used to characterize the properties of VEF in aqueous solution. The VEF molecule is highly flexible in water and conformations can shift between the extended and folded states. The VEF molecule exists in extended state mostly in aqueous solution and the conformations bonded with ACE are also the extended ones. The findings indicate that MD simulations have a good agreement with the molecular docking analysis.     

Dynamics of Hydrogen Bonding in Three-Component Nanorotors

The dynamics of hydrogen bonding do not only play an important role in many biochemical processes but also in Nature's multicomponent machines. Here, a three-component nanorotor is presented where both the self-assembly and rotational dynamics are guided by hydrogen bonding. In the rate-limiting step of the rotational exchange, two phenolic O-H–N,N_{(phenanthroline)} hydrogen bonds are cleaved, a process that was followed by variable-temperature ¹H NMR spectroscopy. Activation data (ΔG^≠₂₉₈=46.7 kJ mol⁻¹ at 298 K, ΔH^≠=55.3 kJ mol⁻¹, and ΔS^≠=28.8 J mol⁻¹ K⁻¹) were determined, furnishing a rotational exchange frequency of k₂₉₈=40.0 kHz. Fully reversible disassembly/assembly of the nanorotor was achieved by addition of 5.0 equivalents of trifluoroacetic acid (TFA)/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) over three cycles.