Trifurcated Hydrogen Bonds Research Articles

Structural multiplicity in a solvated hydrate of the antiretroviral protease inhibitor Lopinavir

Lopinavir is a potent protease inhibitor that is used as a first-line pharmaceutical drug for the treatment of HIV. The multi-component solvated Lopinavir crystal, systematic name (2S)-N-[(2S,4S,5S)-5-[2-(2,6-dimethylphenoxy)acetamido]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide–ethane-1,2-diol–water (8/3/7) 8C37H48N4O5·3C2H6O2·7H2O, was prepared using evaporative methods. The crystalline material obtained from this experimental synthesis was characterized and elucidated by single-crystal X-ray diffraction (SC-XRD). The crystal structure is unusual in that the unit cell contains 18 molecules. The stoichiometric ratio of this crystal is eight Lopinavir molecules [8(C37H48N4O5)], three ethane-1,2-diol molecules [3(C2H6O2)] and seven water molecules [7(H2O)]. The crystal packing features both bi- and trifurcated hydrogen bonds between atoms.

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

The front cover artwork is provided by the TheoCheM group at the Vrije Universiteit Amsterdam. The image shows how, in X- •••H3 C-Y complexes, the Lewis base X- tetrel-binds to the central C while sterically pushing the H atoms towards C; hence, the compression and blueshift of the H-C bonds. Read the full text of the Research Article at 10.1002/cphc.202300480.

Front Cover: Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion (ChemPhysChem 1/2024)

Front Cover: Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion (ChemPhysChem 1/2024)

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

We have quantum chemically investigated the origin of the atypical blueshift of the H-C bond stretching frequency in the hydrogen-bonded complex X- •••H3 C-Y (X, Y=F, Cl, Br, I), as compared to the corresponding redshift occurring in Cl- •••H3 N and Cl- •••H3 C-H, using relativistic density functional theory (DFT) at ZORA-BLYP-D3(BJ)/QZ4P. Previously, this blueshift was attributed, among others, to the contraction of the H-C bonds as the H3 C moiety becomes less pyramidal. Herein, we provide quantitative evidence that, instead, the blueshift arises from a direct and strong X- •••C interaction of the HOMO of A- with the backside lobe on carbon of the low-lying C-Y antibonding σ* LUMO of the H3 C-Y fragment. This X- •••C bond, in essence a tetrel bond, pushes the H atoms towards a shorter H-C distance and makes the H3 C moiety more planar. The blueshift may, therefore, serve as a diagnostic for tetrel bonding.

Main Group Molecular Switches with Swivel Bifurcated to Trifurcated Hydrogen Bond Mode of Action.

Artificial molecular machines have captured the full attention of the scientific community since Jean-Pierre Sauvage, Fraser Stoddart, and Ben Feringa were awarded the 2016 Nobel Prize in Chemistry. The past and current developments in molecular machinery (rotaxanes, rotors, and switches) primarily rely on organic-based compounds as molecular building blocks for their assembly and future development. In contrast, the main group chemical space has not been traditionally part of the molecular machine domain. The oxidation states and valency ranges within the p-block provide a tremendous wealth of structures with various chemical properties. Such chemical diversity─when implemented in molecular machines─could become a transformative force in the field. Within this context, we have rationally designed a series of NH-bridged acyclic dimeric cyclodiphosphazane species, [(μ-NH){PE(μ-NtBu)2PE(NHtBu)}2] (E = O and S), bis-PV2N2, displaying bimodal bifurcated R21(8) and trifurcated R31(8,8) hydrogen bonding motifs. The reported species reversibly switch their topological arrangement in the presence and absence of anions. Our results underscore these species as versatile building blocks for molecular machines and switches, as well as supramolecular chemistry and crystal engineering based on cyclophosphazane frameworks.

Molecular Dynamics Analysis of Stabilities of Transitional Hydrogen Bonds in Sulfate Aqueous Solution

Abstract Different mechanisms of H-bond formation between sulfate anion and water are presented using molecular dynamics simulations. Multi-centered hydrogen bonds were observed. Always the hydrogen bridge making/breaking goes according to the large angular jump mechanism. Moreover, classical, bifurcated and trifurcated hydrogen bonds between water and sulfate have transitional character. This is supported by free energies of binding of water to sulfate ion determined for particular types of hydrogen bridges. This phenomenon is similar to the one observed in the hydration shell of perchlorate anion. Nevertheless the amplitudes of angular jump as well as hydrogen bond lifetimes are different in both cases.

Three new amidophosphoric acid esters with a P(O)[OCH2C(CH3)2CH2O] segment: X-ray diffraction, DFT, AIM and Hirshfeld surface investigations of bi- and tri-furcated (three and four-center) hydrogen bond interactions

AbstractStructural and packing features of three new amidophosphoric acid esters having a common partXP(O)[OCH2C(CH3)2CH2O], withX = [(CH3)3CNH] (1), [(CH3)2HCNH] (2) and [C6H11(CH3)N] (3), are investigated by single crystal X-ray diffraction. The results illustrate that the compounds1and3crystallize with one independent molecule in the asymmetric unit; whereas, for2, the compound crystallizes with three independent molecules in the asymmetric unit. The crystal structures are mostly stabilizedviatri-furcated hydrogen bond interactions (C–H · · ·)2(N–H · · ·)O=P in1and (C–H · · ·)3O=P in3, while the stability is given by bi-furcated hydrogen bond interactions (C–H · · ·)(N–H · · ·)O=P in2. For a better understanding of the nature, strength and energetics associated with the formation of the quoted multi-center hydrogen bond interactions, the Natural Bond Order (NBO) method from Density Functional Theory (DFT) and a topological analysis by means of Atoms In Molecules (AIM) and Hirshfeld surface procedures were performed. These studies reveal that the studied multi-center hydrogen bond interactions of the type O · · · H are favoured in the crystal packing displaying enrichment ratios larger than unity. The detailed nature of the different interactions in these multi-center interactions is studied for the first time in such compounds. It is shown that the N–H · · · O interaction is rather non-covalent closed-shell whereas the C–H · · · O interaction is more van der Waals closed-shell. Stronger hydrogen bond interactions are observed for a lower multiple H-atom acceptor oxygen in three-center hydrogen bond interactions (C–H · · ·)(N–H · · ·)O=P of2than for four-center interactions in1[i.e. (C–H · · ·)2(N–H · · ·)O=P] and3[i.e. (C–H · · ·)3O=P]. The better H-atom acceptability of the O atom of P=O compared with the esteric O atom is explained by the richers-character of the hybrid orbital of the O atom acceptor of P=O coupled with enhance of the polarization and charge. The obtained results are also confirmed by Molecular Electrostatic Potential (MEP).

2]Rotaxanes Bearing a Tetralactam Macrocycle: The Role of a Trifurcated Hydrogen Bond in the Crystalline State

This study investigated the proper classification and quantification of intercomponent trifurcated hydrogen bonds, in the crystalline state, of rotaxanes bearing a tetralactam Leigh‐type macrocycle. Quantum mechanical calculations were carried out to obtain the interaction paths and their stabilization energies. In general, the use and necessity of fragmentation in types of interaction have been reported in the literature, although they are commonly performed only using a geometric approach. This results in N–H···O interactions that are indicated as the main interactions between components, neglecting other possible interactions. The use of energetic fragmentation was demonstrated here under an appropriate demarcation considering all interactions and showing the existence and role of the C–H···O interaction. The C–H···O interactions showed similar energy to N–H···O interactions with average values around –4.75 kcal mol–1and –4.60 kcal mol–1, respectively. This revealed that the three hydrogen bonds are part of a cooperative set of interactions with a similar contribution. The trifurcated hydrogen bonds presented high contribution in the total intercomponent stabilization energy of the rotaxanes, with an average value of 51 % in the studied series.

Conformer Distribution in Rotaxanes Containing Nonsymmetric Threads: A Systematic Approach

Rotaxanes are designated as molecular machines due their different movements. Systematic studies regarding the different conformations adopted by these systems and the factors that lead to the distribution of the conformations, in both solution and the solid state, have not been widely explored, especially for rotaxanes with nonsymmetric stoppers. Therefore, in this study we have investigated three novel [2]rotaxanes containing threads derived from nonsymmetric succinamides [R1R2NC(O)‐CH2CH2‐C(O)NR2R1, with R1/R2 = Bu/Bn, Bu/2‐furylmethyl, and 5‐methylisoxazol‐3‐yl/2‐furylmethyl]. The proportions of rotamers were investigated for threads and rotaxanes by solution and solid‐state NMR spectroscopy as well as by single‐crystal and powder X‐ray diffraction. In solution, the threads present different proportions of conformer, with the E,Z conformation prevailing, whereas only one conformer is observed in the solid state. For the rotaxanes, only one conformer prevails in the single crystal, whereas the solution and solid (bulk) states present more than one rotamer. These proportions are modified when the threads are incorporated into the macrocycle during rotaxane formation. The intramolecular interactions in each rotamer were investigated by QTAIM and variable‐temperature 1H NMR experiments. The changes in conformational population between the threads and respective rotaxanes can be explained by a set of different intramolecular interactions, with trifurcated hydrogen bonds responsible for most of the stabilization energy.

Pyridoxal derivatized copper(II) complexes: Evaluation of antioxidant, catecholase, and DNA cleavage activity

This manuscript describes the synthesis, characterization and structural analysis of copper(II) complexes with pyridoxal-type bidentate ligands, obtained from the condensation between pyridoxal and ortho-halogenated substituted anilines (C1–C5). The complexes C1, C2 and C5 were measured by X-ray single crystal analysis which showed classic and trifurcated hydrogen bonds and interaction as a sigma-hole between the oxygen atoms of the iodine ligand derivative in the complex C5. All compounds were tested as mimetics of superoxide dismutase (SOD), through NBT photoreduction method in aqueous solution of pH 7.8, but the complex C5 showed an expressive IC50 of 0.4 μM.In addition, catecholase-like activity of C1–C5 in the presence of the substrate 3,5-di-tert-butylcatechol and cleavage of plasmid DNA were also evaluated. Again, the best results were associated with the complex C5 containing iodine in the ortho position.

Synthesis, structural characterization, and hydrogen bonds of Co9(OH)14[SO4]2

Abstract The new compound Co9(OH)14[SO4]2 was synthesized using a hydrothermal method from LiF, Na2SO3, and Co(CH3COO)2·4H2O in a molar ratio of 1:1:1 in the presence of atmospheric oxygen. Its crystal structure was determined from single crystal X-ray diffraction data. Co9(OH)14[SO4]2 crystallizes in the triclinic system, space group P1̅ with a=7.693(2) Å, b=8.318(2) Å, c=8.351(2) Å, α=82.375(5)°, β=77.832(4)°, γ=68.395(4)°, V=484.8(2) Å3, and Z=2. Its structure is composed of cobalt-containing sheets interconnected by SO4 tetrahedra. Bent and symmetrically trifurcated hydrogen bonds have been observed. Furthermore, structural similarities with hydrozincite and brucite minerals have been noticed.

Structure of 2,2'-(5-tert-butyl-1,3-phenyl-ene)bis-(1-pentyl-1H-benzimidazol-3-ium) tetra-chlorido-mercurate(II).

In the title salt, (C34H44N4)[HgCl4], the [C34H44N4]2+ cations and [HgCl4]2- anions are linked by N-H⋯Cl hydrogen bonds. One of the two n-pentyl side chains was refined as disordered over two sets of sites, with occupancies of 0.733 (18) and 0.267 (18). The geometry around the HgII atom in the [HgCl4]2- anion is distorted tetra-hedral, with bond angles ranging from 98.16 (3) to 120.68 (3)°. In the [HgCl4]2- anion, there are two short Hg-Cl bonds [2.4120 (9) and 2.4171 (11) Å], one inter-mediate Hg-Cl bond [2.4716 (12) Å] and one long Hg-Cl bond [2.6579 (13) Å] for the Cl atom involved in a trifurcated hydrogen bond as an acceptor, including two N-H⋯Cl⋯H-N interactions as well as one C-H⋯Cl inter-action. There are several C-H⋯Cl inter-actions, with C⋯Cl distances ranging from 3.492 (3) to 3.796 (3) Å. These link the cations and anions into a zigzag chain along the c-axis direction. In addition, there are Cl⋯Cl halogen bonds, as well as π-π inter-actions, with centroid-to-centroid distances of 3.4765 (18) Å, which link one of the two benzimidazole moieties into dimeric units.

Multi-centred hydrogen bonds between water and perchlorate anion

ABSTRACTResults of classical molecular dynamics simulations are presented for the re-orientational dynamics of water hydrogen bonded to perchlorate anion. Different mechanisms of bond formation are presented. Due to its regular tetrahedron geometry the perchlorate anion can make classical as well as bifurcated and trifurcated hydrogen bonds. The angular variation of water in the first solvation shell of perchlorate suggests the transitional character of multi-centred hydrogen bonds. As a result water molecules can slide around the anion.

A cadaveric study on the variant branching pattern of internal iliac artery

The molecular structure of 1:2:1 adduct of diprotonated 1,4-diazabicyclo[2.2.2]octane, (DABCO), hydrogen squarates (HSQ−) and water (1) has been characterized by single-crystal X-ray diffraction and infrared spectroscopy. The crystals of 1 are orthorhombic, space group Pnma. The non-equivalent HSQ− anions are bonded into zigzag chains (α-chain) by two short OH⋯O hydrogen bonds of 2.485(2) and 2.509(2) Å, and additionally H-bonded by water molecules linking the zigzag chains into ribbons. The diprotonated DABCO cations are located between the ribbons and interact with HSQ− anions by the NH⋯O trifurcated hydrogen bonds. The FTIR spectrum shows a very broad absorption in the 1740–550 cm−1 region, typical of short hydrogen bonds and it is attributed to the ν(OHO) and γ(OHO) vibrations. The second derivative spectrum distinguishes the νCO and γCC modes assigned to the π-delocalized squaric acid ring.

Transitional hydrogen bonds in aqueous perchlorate solution.

Different mechanisms of H-bond formation between perchlorate anions and water are presented using the molecular dynamics simulations. The detailed methods in searching for multi-centered hydrogen bonds are proposed. The time evolution of H-bond geometric parameters for classical, bifurcated and trifurcated hydrogen bonds in the aqueous perchlorate solution indicates the transitional character of hydrogen bridges as well as the rigid nature of the solvation structure formed by the ion and its first solvation shell. This is supported by the values of free energy binding of water to perchlorate ions determined for particular types of hydrogen bridges.

STRUCTURE OF (2E,2'E)-3,3'-(1,3-PHENYLENE)BIS(1-(ANTHRACEN-9-YL)PROP-2-EN-1-ONE): A CHALCONE DERIVATIVE

The title compound C 40 H 26 O 2 [(2 E , 2' E )-3, 3'-(1,3-Phenylene)-bis(1-(anthracen-9-yl)prop-2-en-1-one)] was prepared from the reaction of isophthalaldehyde and 9-acetylanthracene treated with solution of ethanol and sodium hydroxide. It has been crystallized from DMF using slow evaporation method in the triclinic space group P-1 with Z=2 and unit cell parameters, a = 9.8276(8) b = 10.7470(8), c = 14.5606(10) A, α= 99.833(6), β=104.495(6) & ϒ= 97.371(6)o. The architecture of the crystal structure is determined mainly by three intermolecular interactions [C23-H10…O1, C25-H15…O1, C16-H17…O1], here O1 acts as an acceptor to three different carbon atoms, resulting into the formation of a trifurcated hydrogen bond, forming a graph set motif R 2 2 (8) through a pair of C25-H15...O1 interactions. These motifs are further extended through another intermolecular hydrogen bond [C3-H6...O2] forming a ladder like network, extending along the c-axis.

C–H···BF2O2Interactions in Crystals: A Case for Boron Hydrogen Bonding?

Molecules bearing the borondifluoride unit represent an important class of dyes. We report the intriguing occurrence of short H···B contacts in the crystal structure of compounds featuring the BF2O2 fragment. Using density functional theory-based calculations, we discovered that, in contrast to what is suggested by the structural observation, the driving force behind these short H···B contacts is not a direct H···B interaction but it relies on the existence of a combination of single, bifurcated, or trifurcated hydrogen bond paths that are practically isoenergetic within a broad range of C–H···B interaction orientations. The BF2O2 group as a whole displays a very isotropic hydrogen bonding ability and, in turn, a strong adaptability to structural requirements in the solid state.

Various Coordination Modes of Sulfate by Cyanuric Acid Platform‐Based First‐ and Second‐Generation Urea Receptors

Cyanuric acid platform-based first-generation p-nitrophenyl- (L1), p-cyanophenyl- (L2) and pentafluorophenyl- (L3) substituted tris-ureas and second-generation p-nitrophenyl-functionalized hexakis-urea receptor (L4) have been synthesized. Detailed solid-state structural studies on the binding of sulfate to L1, L2 and L4 have been examined thoroughly by single-crystal X-ray diffraction and compared with the binding modes of SO 4 2– to the pentafluorophenyl analogue of the tris-urea receptor L3 to evaluate the various modes of SO 4 2– binding in this new generation of cyanuric acid platform-based anion receptors. The crystallographic results show a 1:1 binding pattern between L1 and SO 4 2– through six N–H···O interactions with the three urea moieties of the receptor and one C–H···O interaction with one of the tetrabutylammonium counter cations in complex 1. Thus, this complex shows an uncommon example of a seven-coordinate SO 4 2– , which is structurally similar to that of the sulfate-binding protein (SBP). Interestingly, L2 shows a 2:1 host/guest binding pattern with SO 4 2– that generates a dimeric capsular assembly with dimensions of approximately 10.398 A in complex 2. In this case, each of the oxygen atoms of SO 4 2– forms a trifurcated hydrogen bond with the urea NH groups and thus a total of 12 N–H···O hydrogen-bonding interactions can be observed for SO 4 2– . In contrast, L3 shows 11 hydrogen-bonding interactions with the encapsulated SO 4 2– in complex 3 assisted by two nBu 4 N + counter cations through six N–H···O and five C–H···O interactions. In the case of the SO 4 2– complex of L4, complex 4 shows 1:1 encapsulation of SO 4 2– in its inner cavity with 10 N–H···O interactions. A binding study of SO 4 2– in solution was performed with L4 in dmso by isothermal titration calorimetry (ITC). This study also showed a 1:1 binding pattern of SO 4 2– with an association constant of approximately 5.11 (log K). Furthermore, the binding of SO 4 2– in the gas phase was examined by ESI mass spectrometry.

Water Encapsulation in a Polyoxapolyaza Macrobicyclic Compound

A new heteroditopic macrobicyclic compound (t(2)pN(5)O(3)) containing two separate polyoxa and polyaza compartments was synthesized in good yield through a [1 + 1] "tripod-tripod coupling" strategy. The X-ray crystal structure of H(3)t(2)pN(5)O(3)(3+) revealed the presence of one encapsulated water molecule accepting two hydrogen bonds from two protonated secondary amines and donating a hydrogen bond to one amino group. The acid-base behavior of the compound was studied by potentiometry at 298.2 K in aqueous solution and at ionic strength 0.10 M in KCl. The results revealed unusual protonation behavior, namely a surprisingly low fourth protonation constant contrary to what was expected for the compound. (1)H NMR and DOSY experiments, as well as molecular modeling studies, showed that the water encapsulation and the conformation observed in the solid state are retained in solution. The strong binding of the encapsulated water molecule, reinforced by the cooperative occurrence of a trifurcated hydrogen bond at the polyether compartment of the macrobicycle, account for the very low log K(4)(H) value obtained.

Dicobalt(II) lead(II) hydrogenphos-phate(V) phos-phate(V) hydroxide monohydrate.

The title compound, Co2Pb(HPO4)(PO4)OH·H2O, which was synthesized under hydro­thermal conditions, crystallizes in a new structure type. Except for two O atoms in general positions and two Co atoms on centres of symmetry, all other atoms in the asymmetric unit (1 Pb, 2 Co, 2 P, 8 O and 4 H) are located on mirror planes. The structure is built up from two infinite linear chains, viz. 1 ∞[CoO2/1(H2O)2/2O2/2] and 1 ∞[CoO2/1(OH)2/2O2/2], of edge-sharing CoO6 octa­hedra running along [010]. Adjacent chains are linked to each other through PO4 and PO3(OH) tetra­hedra, leading to the formation of layers parallel to (100). The three-dimensional framework is formed by stacking along [100] of adjacent layers that are held together by distorted PbO8 polyhedra. Hydrogen bonds of the type O—H⋯O involving the water mol­ecule are very strong, while those O atoms involving the OH groups form weak bifurcated and trifurcated hydrogen bonds.