Water Triggers Hydrogen-Bond-Network Reshaping in the Glycoaldehyde Dimer

Carbohydrates are ubiquitous biomolecules in nature. The vast majority of their biomolecular activity takes place in aqueous environments. Molecular reactivity and functionality are, therefore, often strongly influenced by not only interactions with equivalent counterparts, but also with the surrounding water molecules. Glycoaldehyde (Gly) represents a prototypical system to identify the relevant interactions and the balance that governs them. Here we present a broadband rotational-spectroscopy study on the stepwise hydration of the Gly dimer with up to three water molecules. We reveal the preferred hydrogen-bond networks formed when water molecules sequentially bond to the sugar dimer. We observe that the dimer structure and the hydrogen-bond networks at play remarkably change upon the addition of just a single water molecule to the dimer. Further addition of water molecules does not significantly alter the observed hydrogen-bond topologies.     

Hydrogen‐Bond‐Regulated Distinct Functional‐Group Display at the Inner and Outer Wall of Vesicles

A unique supramolecular strategy enables the unidirectional assembly of two bola‐shaped unsymmetric π‐amphiphiles, NDI‐1 and NDI‐2, which feature a naphthalene–diimide chromophore connected to nonionic and anionic head groups on opposite arms. The amphiphiles differ only in the location of a hydrazide group, which is placed either on the nonionic or on the anionic arm of NDI‐1 and NDI‐2, respectively. The formation of hydrogen bonds between the hydrazides, which compensates for electrostatic and steric factors, promotes unidirectional alignment and the formation of monolayer vesicles. The zeta potentials and cation‐assisted quantitative precipitation reveal negatively charged and nonionic outer surfaces for NDI‐1 and NDI‐2, respectively, indicating that hydrogen bonding also dictates the directionality of the monolayer curvature, ensuring that in both cases, the hydrazides remain at the inner wall to benefit from stronger hydrogen bonding where they are in closer proximity. This is reflected in their different abilities to inhibit α‐chymotrypsin, which possesses a positively charged surface: NDI‐1 induced an inhibition of 80 % whereas hardly any inhibition was observed with NDI‐2.     

The C-F⋅⋅⋅H-C “Anti-Hydrogen Bond” in the Gas Phase: Microwave Structure of the Difluoromethane Dimer

A shortening of the C−H bond lengths and a blue shift of the C−H stretching frequencies for the C-F⋅⋅⋅H-C groups indicates that anti-hydrogen bonds are present the difluoromethane dimer. The most stable conformer has three such interactions (shown schematically).     

Multicomponent Oxyalkylation of Styrenes Enabled by Hydrogen‐Bond‐Assisted Photoinduced Electron Transfer

Herein, we disclose a strategy for the activation of N‐(acyloxy)phthalimides towards photoinduced electron transfer through hydrogen bonding. This activation mode enables efficient access to C(sp³)‐centered radicals upon decarboxylation from bench‐stable and readily available substrates. Moreover, we demonstrate that the formed alkyl radicals can be successfully employed in a novel redox‐neutral method for constructing sp³−sp³ bonds across styrene moieties that gives straightforward access to complex alcohol and ether scaffolds.     

Activation of Electron‐Deficient Quinones through Hydrogen‐Bond‐Donor‐Coupled Electron Transfer

Quinones are important organic oxidants in a variety of synthetic and biological contexts, and they are susceptible to activation towards electron transfer through hydrogen bonding. Whereas this effect of hydrogen bond donors (HBDs) has been observed for Lewis basic, weakly oxidizing quinones, comparable activation is not readily achieved when more reactive and synthetically useful electron‐deficient quinones are used. We have successfully employed HBD‐coupled electron transfer as a strategy to activate electron‐deficient quinones. A systematic investigation of HBDs has led to the discovery that certain dicationic HBDs have an exceptionally large effect on the rate and thermodynamics of electron transfer. We further demonstrate that these HBDs can be used as catalysts in a quinone‐mediated model synthetic transformation.     

Hydrogen‐Bond‐Mediated Asymmetric Catalysis

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single‐step and multiple‐step cascade reactions. These functionalities, which have the ability to afford efficient H‐bond activation of electrophiles including C?O, C?N, aziridines, and epoxides, have established their status as “privileged” functional groups in the design of organocatalysts.     

Hydrogen‐Bond‐Driven Controlled Molecular Marriage in Covalent Cages

A supramolecular approach that uses hydrogen‐bonding interaction as a driving force to accomplish exceptional self‐sorting in the formation of imine‐based covalent organic cages is discussed. Utilizing the dynamic covalent chemistry approach from three geometrically similar dialdehydes ( A , B , and D ) and the flexible triamine tris(2‐aminoethyl)amine ( X ), three new [3+2] self‐assembled nanoscopic organic cages have been synthesized and fully characterized by various techniques. When a complex mixture of the dialdehydes and triamine X was subjected to reaction, it was found that only dialdehyde B (which has OH groups for H‐bonding) reacted to form the corresponding cage B₃X₂ selectively. Surprisingly, the same reaction in the absence of aldehyde B yielded a mixture of products. Theoretical and experimental investigations are in complete agreement that the presence of the hydroxyl moiety adjacent to the aldehyde functionality in B is responsible for the selective formation of cage B₃X₂ from a complex reaction mixture. This spectacular selection was further analyzed by transforming a nonpreferred (non‐hydroxy) cage into a preferred (hydroxy) cage B₃X₂ by treating the former with aldehyde B . The role of the H‐bond in partner selection in a mixture of two dialdehydes and two amines has also been established. Moreover, an example of unconventional imine bond metathesis in organic cage‐to‐cage transformation is reported.     

Molecular Conductance through a Quadruple‐Hydrogen‐Bond‐Bridged Supramolecular Junction

A series of self‐complementary ureido pyrimidinedione (UPy) derivatives modified with different aurophilic anchoring groups were synthesized. Their electron transport properties through the quadruple hydrogen bonds in apolar solvent were probed employing the scanning tunneling microscopy break junction (STMBJ) technique. The molecule terminated with a thiol shows the optimal electron transport properties, with a statistical conductance value that approaches 10^?3 G₀. The ¹H NMR spectra and control experiments verify the formation of quadruple hydrogen bonds, which can be effectively modulated by the polarity of the solvent environment. These findings provide a new design strategy for supramolecular circuit elements in molecular electronics.     

Werner Complexes with ω‐Dimethylaminoalkyl Substituted Ethylenediamine Ligands: Bifunctional Hydrogen‐Bond‐Donor Catalysts for Highly Enantioselective Michael Additions

The racemic carbonate complex [Co(en)₂O₂CO]⁺ Cl^? (en=1,2‐ethylenediamine) and (S)‐[H₃NCH((CH₂)_nNHMe₂)CH₂NH₃]³⁺ 3 Cl^? (n=1–4) react (water, charcoal, 100 °C) to give [Co(en)₂((S)‐H₂NCH((CH₂)_nNHMe₂)CH₂NH₂)]⁴⁺ 4 Cl^? ( 3 a – d H⁴⁺ 4 Cl^?) as a mixture of Λ/Δ diastereomers that separate on chiral‐phase Sephadex columns. These are treated with NaOH/Na⁺ BAr_f^? (BAr_f=B(3,5‐C₆H₃(CF₃)₂)₄) to give lipophilic Λ‐ and Δ‐ 3 a–d ³⁺ 3 BAr_f^?, which are screened as catalysts (10 mol %) for additions of dialkyl malonates to nitroalkenes. Optimal results are obtained with Λ‐ 3 c ³⁺ 3 BAr_f^? (CH₂Cl₂, ?35 °C; 98–82 % yields and 99–93 % ee for six β‐arylnitroethenes). The monofunctional catalysts Λ‐ and Δ‐[Co(en)₃]³⁺ 3 BAr_f^? give enantioselectivities of <10 % ee with equal loadings of Et₃N. The crystal structure of Δ‐ 3 a H⁴⁺ 4 Cl^? provides a starting point for speculation regarding transition‐state assemblies.     

Small‐Molecule Recognition for Controlling Molecular Motion in Hydrogen‐Bond‐Assembled Rotaxanes

Di(acylamino)pyridines successfully template the formation of hydrogen‐bonded rotaxanes through five‐component clipping reactions. A solid‐state study showed the participation of the pyridine nitrogen atom in the stabilization of the mechanical bond between the thread and the benzylic amide macrocycle. The addition of external complementary binders to a series of interlocked bis(2,6‐di(acylamino)pyridines) promoted restraint of the back and forward ring motion. The original translation can be restored through a competitive recognition event by the addition of a preorganized bis(di(acylamino)pyridine) that forms stronger ADA–DAD complexes with the external binders.     

Anticancer Activity of Hydrogen‐Bond‐Stabilized Half‐Sandwich RuII Complexes with Heterocycles

Neutral half‐sandwich organometallic ruthenium(II) complexes of the type [(η⁶‐cymene)RuCl₂(L)] ( H1 – H10 ), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single‐crystal X‐ray diffraction confirming a piano‐stool geometry with η⁶ coordination of the arene ligand. Hydrogen bonding between the N? H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal–ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework ( H1 ) or mercaptobenzoxazole ( H6 ) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1‐phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non‐intercalative fashion and cause unwinding of plasmid DNA in a cell‐free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen‐bond donor on the heterocycle reduces the cytotoxicity.     

Hydrogen‐Bond‐Selective Phase Transfer of Nanoparticles across Liquid/Gel Interfaces

In the swim : Colloidal nanoparticles coated with polylactide (PLA, red) and poly(ethylene glycol) brushes (PEG, black) can transfer from organic to aqueous phases across liquid/liquid or liquid/gel interfaces during degradation of the PLA coating (see picture: first step), which is driven selectively by the hydrogen bonding of the PEG coating with the aqueous phase (second step).

     

Hydrogen‐Bond‐Based Magnetic Exchange Between μ‐Diethylnicotinamide(aqua)bis(X‐salicylato)copper(II) Polymeric Chains

Polymeric salicylatocopper(II) complexes of unusual composition [C u(X‐ sal)₂( μ‐denia)(H₂O)]_n [denia = diethylnicotinamide, and X‐sal = 5‐methylsalicylate ( 1 ), 3‐methylsalicylate ( 2 ), 4‐methoxysalicylate ( 3 ), 3,5‐dichlorosalicylate ( 4 ) and 3,5‐dibromosalicylate ( 5 )] were synthesized and characterized. Magnetic measurements were performed in the temperature range 1.8–300 K. The structural unit of all complexes consists of a Cu^II atom, which is monodentately coordinated by the pair of X‐salicylate anions in trans positions. Water and the diethylnicotinamide ligand occupy the other two basal plane positions of the tetragonal pyramid. The axial positions are occupied by a diethylnicotinamide oxygen atom of neighboring structural units, thus forming a spiral polymeric structure parallel to b axis. Magnetic measurements showed that all complexes 1 – 5 exhibit a susceptibility maximum at about 6–8 K. The obtained data fit to Bleaney–Bowers equation gave singlet‐triplet energy gaps 2J = –8.60 cm^–1 for 1 , 2J = –6.57 cm^–1 for 2 , 2J = –8.57 cm^–1 for 3 , 2J = –6.82 cm^–1 for 4 , and 2J = –6.45 cm^–1 for 5 . The supramolecular structure based on hydrogen bonds [described by supramolecular synthons R₂²(10) and R₂²(12)] is the pathway for antiferromagnetic interactions of the magnetically coupled pairs of copper atoms of neighboring chains within the 2D supramolecular layers. The results of the magnetic measurements suggest involvement of the COO groups in the magnetic interaction pathway for all five complexes.     

Axial and Equatorial Hydrogen Bonds in the Tetrahydropyran⋅⋅⋅HCl Dimer

Two hydrogen-bond complexes formed between tetrahydropyran and hydrogen chloride have been observed by using a molecular beam Fourier transform microwave spectrometer. The rotation constants are consistent with C_s symmetry, with HCl pointing to the domain of the axial and equatorial lone pair at the oxygen atom (shown on the left and right, respectively). The axial form has been found to be the more stable one.     

Role of Hydrogen‐Bonding Acceptors in Organo‐Enamine Catalysis

A hydrogen bond acceptor plays an important role in the catalytic cycle of organo‐enamine catalysis. It can effectively influence the rate of reaction through hydrogen bonding interaction with enammonium (N‐protonated enamine intermediate). Our findings are supported by both kinetic experiments and quantum chemical calculations.     

Solvent Effects on the Monomer/Hydrogen‐Bonded Dimer Equilibrium in Carboxylic Acids: (+)‐(S)‐Ketopinic Acid as a Case Study

The hydrogen‐bond‐assisted self‐association process of a chiral semirigid carboxylic acid, namely, (+)‐(S)‐ketopinic acid, has been studied. The multiconformational monomer/dimer equilibrium has been evaluated by means of a concentration‐dependent FTIR study that enabled the experimental equilibrium constants of the dimer formation reaction (K_dim) to be determined in two solvents of different polarity. In CDCl₃, dimeric forms predominate, even in diluted solutions ( =5.074), whereas in CD₃CN the self‐association process is hindered and monomers are always the main species, irrespective of solute concentration ( =0.194). The reliability of the dimerization constants and the derived mono‐ and dimeric experimental fractions have been proven by means of accurate matching between the experimental vibrational circular dichroism spectra of the species and the theoretical spectra generated by considering the simultaneous weighted contributions of the concomitant monomers and dimers.