Intramolecular H-bonding Interactions Research Articles

Enhanced Reactivities of Iron(IV)-Oxo Porphyrin Species in Oxidation Reactions Promoted by Intramolecular Hydrogen-Bonding.

High-valent iron-oxo species are one of the common intermediates in both biological and biomimetic catalytic oxidation reactions. Recently, hydrogen-bonding (H-bonding) has been proved to be critical in determining the selectivity and reactivity. However, few examples have been established for mechanistic insights into the H-bonding effect. Moreover, intramolecular H-bonding effect on both C-H activation and oxygen atom transfer (OAT) reactions in synthetic porphyrin model system has not been investigated yet. In this study, a series of heme-containing iron(IV)-oxo porphyrin species with or without intramolecular H-bonding are synthesized and characterized. Kinetic studies revealed that intramolecular H-bonding can significantly enhance the reactivity of iron(IV)-oxo species in OAT, C-H activation, and electron-transfer reactions. This unprecedented unified H-bonding effect is elucidated by theoretical calculations, which showed that intramolecular H-bonding interactions lower the energy of the anti-bonding orbital of iron(IV)-oxo porphyrin species, resulting in the enhanced reactivities in oxidation reactions irrespective of the reaction type. To the best of the knowledge, this is the first extensive investigation on the intramolecular H-bonding effect in heme system. The results show that H-bonding interactions have a unified effect with iron(IV)-oxo porphyrin species in all three investigated reactions.

Crown-hydroxylamines are pH-dependent chelating N,O-ligands with a potential for aerobic oxidation catalysis

Despite the rich coordination chemistry, hydroxylamines are rarely used as ligands for transition metal coordination compounds. This is partially because of the instability of these complexes that undergo decomposition, disproportionation and oxidation processes involving the hydroxylamine motif. Here, we design macrocyclic poly-N-hydroxylamines (crown-hydroxylamines) that form complexes containing a d-metal ion (Cu(II), Ni(II), Mn(II), and Zn(II)) coordinated by multiple (up to six) hydroxylamine fragments. The stability of these complexes is likely to be due to a macrocycle effect and strong intramolecular H-bonding interactions between the N−OH groups. Crown-hydroxylamine complexes exhibit interesting pH-dependent behavior where the efficiency of metal binding increases upon deprotonation of the hydroxylamine groups. Copper complexes exhibit catalytic activity in aerobic oxidation reactions under ambient conditions, whereas the corresponding complexes with macrocyclic polyamines show poor or no activity. Our results show that crown-hydroxylamines display anomalous structural features and chemical behavior with respect to both organic hydroxylamines and polyaza-crowns.

Geometric control of Cu, Ni and Pd complexes in the solid state via intramolecular H-bonding interactions

In this article, we describe the synthesis and characterization of a family of copper, nickel and palladium complexes bound by bidentate ligands derived from ortho-phenylenediamine that contain tunable H-bond donors. The crystal structures of the reduced dianionic metal complexes (formulated as [MII(L2-)2]2-) depict intramolecular H-bonding interaction between the two ligand scaffolds. Variations on the primary (Cu, Ni, Pd), secondary (H-bonding donor) and tertiary coordination sphere (solvent of crystallization and countercation), led to the isolation of the metal complexes in square-planar (SP) and/or twisted pseudo-tetrahedral geometry (TW). A detailed structural analysis of the complexes in the solid state revealed that the intramolecular H-bonding interactions can be altered by disrupting the bonds between the countercation, solvent of crystallization and the ligand scaffold, which leads to changes in the geometry of the complexes (SP or TW). DFT calculations are in agreement with our experimental observations, in which the Cu complexes were found to favor twisted geometries while the Ni and Pd complexes favored square-planar geometries.

Interactions of arylhydroxylamines and alkylaldoximes with a rhodium porphyrin

Heme enzymes are involved in the binding and metabolism of hydroxylamine (RNHOH) and aldoxime (RCH=NOH) compounds (R = H, alkyl, aryl). We report the synthesis and X-ray crystal structure of a metalloporphyrin in complex with an arylhydroxylamine, namely that of (TPP)Rh(PhNHOH)(C6H4Cl) (TPP = tetraphenylpophryinato dianion). The crystal structure reveals, in addition to N-binding of PhNHOH to Rh, the presence of an intramolecular H-bond between the hydroxylamine –OH proton and a porphyrin N-atom. Results from density functional theory (DFT) calculations support the presence of this intramolecular H-bond in this global minimum structure, and a natural bond order (NBO) analysis reveals that this H-bond comprises a donor π N=C (porphyrin) to acceptor σ* O–H (hydroxylamine) interaction of 2.32 kcal/mol. While DFT calculations predict the presence of similar intramolecular H-bond interactions in the related aldoxime complexes (TPP)Rh(RCH=NOH)(C6H4Cl) in their global minima structures, the X-ray crystal structure obtained for the (TPP)Rh(CH3(CH2)2CH=NOH)(C6H4Cl) complex is consistent with the local (non-global) minima conformation that does not have this intramolecular H-bond interaction.

Crystal structure and cation-anion interactions of potassium (Difluoromethanesulfonyl) (trifluorome thanesulfonyl)imide.

Sulfonimide salts are of great interest for battery use thanks to their special properties including sufficient superior chemical/thermal stabilities, structural flexibility, etc. In particular, the hydrogen-containing sulfonimide (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide anion {[N(SO2CF2H) (SO2CF3)]-, DFTFSI-}, stands out owing to its suppressed anion mobility and superior electrochemical properties. We herein report the structural analyses of potassium (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide {K [N(SO2CF2H) (SO2CF3)], KDFTFSI} by virtue of single crystal X-ray diffraction and computational approaches. Our results reveal that KDFTFSI crystallizes in a orthorhombic cell (space group: Pbcn) comprising of cationic and anionic layers, which is similar to the conventional sulfonimide salt, potassium bis(trifluoromethanesulfonyl)imide {K [N(SO2CF3)2], KTFSI}. Gas-phase density functional theory calculations show that the conversion from trans to cis DFTFSI- anions is hindered due to the presence of stabilizing intramolecular H-bonding interactions in the trans conformer; yet interaction with K+ substantially minimizes the energy difference between the two conformers due to the formation of strong tridentate K+ coordination with oxygen atoms in the cis KDFTFSI. This work is anticipated to provide further understanding on the structure-property relations of hydrogenated sulfonimide anions, and thus inspire the structural design of new anions for battery research.

Conformationally Locked Cyclo[2]Dipyrrins Linked with Anthracene Subunits: Synthesis and Chiroptical Properties.

Herein, we report the synthesis of anthracene-containing twisted cyclo[2]dipyrrin 1 by utilizing a non-planar building block, 1,5-dipyrrylanthracene (1,5-DPA). The non-planar nature of the macrocycle enhanced the solubility and helped in structural characterization. Macrocycle 1 adopts a twisted 'figure of eight' conformation stabilized by strong intramolecular H-bonding interactions and exists as a pair of helical enantiomers, as revealed by X-ray crystallographic analysis. More importantly, the sterically locked structure enabled facile optical resolution using chiral HPLC. The (P,P) and (M,M) enantiomers show moderate chiroptical properties, such as absorption dissymmetry factors |gabs | in the order of 10-3 , and luminescence dissymmetry factors |glum | of 3.8×10-3 and 2.9×10-3 at 702 nm, respectively.

Breaking the DFT Energy Bias Caused by Intramolecular Hydrogen-Bonding Interactions with MESSI, a Structural Elucidation Method Inspired by Wisdom of the Crowd Theory.

The use of quantum-based NMR methods to complement and guide the connectivity and stereochemical assignment of natural and unnatural products has grown enormously. One of the unsolved problems is related to the improper calculation of the conformational landscape of flexible molecules that have functional groups capable of generating a complex network of intramolecular H-bonding (IHB) interactions. Here we present MESSI (Multi-Ensemble Strategy for Structural Identification), a method inspired by the wisdom of the crowd theory that breaks with the traditional mono-ensemble approach. By including independent mappings of selected artificially manipulated ensembles, MESSI greatly improves the sense of the assignment by neutralizing potential energy biases.

Recognition-Encoded Synthetic Information Molecules.

ConspectusNucleic acids represent a unique class of highly programmable molecules, where the sequence of monomer units incorporated into the polymer chain can be read through duplex formation with a complementary oligomer. It should be possible to encode information in synthetic oligomers as a sequence of different monomer units in the same way that the four different bases program information into DNA and RNA. In this Account, we describe our efforts to develop synthetic duplex-forming oligomers composed of sequences of two complementary recognition units that can base-pair in organic solvents through formation of a single H-bond, and we outline some general guidelines for the design of new sequence-selective recognition systems.The design strategy has focused on three interchangeable modules that control recognition, synthesis, and backbone geometry. For a single H-bond to be effective as a base-pairing interaction, very polar recognition units, such as phosphine oxide and phenol, are required. Reliable base-pairing in organic solvents requires a nonpolar backbone, so that the only polar functional groups present are the donor and acceptor sites on the two recognition units. This criterion limits the range of functional groups that can be produced in the synthesis of oligomers. In addition, the chemistry used for polymerization should be orthogonal to the recognition units. Several compatible high yielding coupling chemistries that are suitable for the synthesis of recognition-encoded polymers are explored. Finally, the conformational properties of the backbone module play an important role in determining the supramolecular assembly pathways that are accessible to mixed sequence oligomers.Almost all complementary homo-oligomers will form duplexes provided the product of the association constant for formation of a base-pair and the effective molarity for the intramolecular base-pairing interactions that zip up the duplex is significantly greater than one. For these systems, the structure of the backbone does not play a major role, and the effective molarities for duplex formation tend to fall in the range 10-100 mM for both rigid and flexible backbones. For mixed sequences, intramolecular H-bonding interactions lead to folding. The competition between folding and duplex formation depends critically on the conformational properties of the backbone, and high-fidelity sequence-selective duplex formation is only observed for backbones that are sufficiently rigid to prevent short-range folding between bases that are close in sequence. The final section of the Account highlights the prospects for functional properties, other than duplex formation, that might be encoded with sequence.

Quantitative Measurement of Cooperativity in H-Bonded Networks.

Cooperative H-bonding interactions are a feature of supramolecular networks involving alcohols. A family of phenol oligomers, in which the hydroxyl groups form intramolecular H-bonds, was used to investigate this phenomenon. Chains of intramolecular H-bonds were characterized using nuclear magnetic resonance (NMR) spectroscopy in solution and X-ray crystallography in the solid state. The phenol oligomers were used to make quantitative measurements of the effects of the intramolecular interactions on the strengths of intermolecular H-bonding interactions between the H-bond donor on the end of the chain and a series of H-bond acceptors. Intramolecular H-bonding interactions in the chain increase the strength of a single intermolecular H-bond between the terminal phenol and quinuclidine by up to 14 kJ mol-1 in the n-octane solution. Although the magnitude of the effect increases with the length of the H-bonded chain, the first intramolecular H-bond has a much larger effect than subsequent interactions. H-bond cooperativity is dominated by pairwise interactions between nearest neighbors, and longer range effects are negligible. The results were used to develop a simple model for cooperativity in H-bond networks using an empirical parameter κ to quantify the sensitivity of the H-bond properties of a functional group to polarization. The value of κ measured in these systems was 0.33, which means that formation of the first H-bond increases the polarity of the next H-bond donor in the chain by 33%. The cumulative cooperative effect in longer H-bonded chains reaches an asymptotic value, which corresponds to a maximum increase in the polarity of the terminal H-bond donor of 50%.

Intramolecular Hydrogen Bonding in Thermally Activated Delayed Fluorescence Emitters: Is There Evidence Beyond Reasonable Doubt?

Intramolecular hydrogen bonding between donor and acceptor segments in thermally activated delayed fluorescence (TADF) materials is now frequently employed to—purportedly—rigidify the structure and improve the emission performance of these materials. However, direct evidence for these intramolecular interactions is often lacking or ambiguous, leading to assertions that are largely speculative. Here we investigate a series of TADF-active materials incorporating pyridine, which bestows the potential ability to form intramolecular H-bonding interactions. Despite possible indications of H-bonding from an X-ray analysis, an array of other experimental investigations proved largely inconclusive. Instead, after examining computational potential energy surfaces of the donor–acceptor torsion angle we conclude that the pyridine group primarily alleviates steric congestion in our case, rather than enabling an H-bond interaction as elsewhere assumed. We suggest that many previously reported “H-bonding” TADF materials featuring similar chemical motifs may instead operate similarly and that investigation of potential energy surfaces should become a key feature of future studies.

Synthesis, crystal feature and spectral characterization of paeonol derived Schiff base ligands and their Cu(II) complexes with antimicrobial activity

Four novel Schiff bases PNL-4OMe, PNL-4Br, PNL-4F, PNL-3,4-F2, and their copper(II) complex with [M(L)2(H2O)2] arrangement was synthesized using Paeonol and various aromatic substituted amines. Characterization has been done through FT-IR, ESI Mass, TG-DTA, DFT, magnetic measurements, elemental analysis, and Thermogravimetric analysis. Paeonol derived new bond formation in Schiff bases and changes in frequencies during complexation have been confirmed through FT-IR spectra. All complexes are thermally stable, paramagnetic, and have non-electrolytic behavior. The antimicrobial activity was also tested against Gram-positive bacteria; S. aureus, B. subtilis, and Gram-negative bacteria; E. coli, P. aeruginosa. Single-crystal X-ray data provide evidence that PNL-3,4-F2 is recrystallizing in a triclinic system with P-1(2) space group and confirms the intramolecular H-bonding and short Vander Waal type interactions. Non-covalent interactions and π … π stacking surface interactions in PNL-3,4-F2 were studied with Hirshfeld analysis. H-atoms have the highest interactions with other atoms of neighbouring molecules compared to all other atoms. DFT calculations were performed on the electronic structure of ligand PNL-3,4-F2 and its copper(II) complex and discussed.

Interplay of the intermolecular and intramolecular interactions in stabilizing the thione-based copper(I) complexes and their significance in protecting the biomolecules against metal-mediated oxidative damage

The synthesis, characterization, and X-ray structure of a series of mono, tri, and polynuclear copper complexes of benzimidazole-based N-substituted thiones, BzMeSH (10) and BzOHSH (11), and N,N'-disubstituted, BzMeSMe (12) and BzOHSMe (13) are reported here. The X-ray structure analyses of the copper-thione complexes have revealed that the coordination behaviour and the geometry of the central metal ion in these complexes are significantly dependent on the type of the counter anion used in the reaction. For instance, the reactions of benzimidazole-based thiones with CuCl2 afforded mononuclear trigonal planar Cu(I) complexes 14, 15, 18, and 19. On contrast, upon reaction with CuSO4, 10 afforded the trinuclear copper complex 16, in which thione 10 acts as a bridging as well as terminal ligand, leading to the formation of a six-membered Cu3S3 cluster. The chair-form of six-membered Cu3S3 ring is further stabilized by six intramolecular H-bonding interactions, with overall stabilization energy of 19.28 kcal.mol−1, between the free NH group of 10 and O atom of the counter anion SO42–. Whereas, when thione 10 was reacted with CuI, a 1D-polymeric chain-like copper complex 17 was obtained as a thermodynamically stable product, in which both 10 and iodine act as bridging ligand. The 3D network of complexes has revealed that these copper-thione compounds are stabilized by the presence of various types of intermolecular and intramolecular H-bonding and π − π stacking interactions in the solid state. NBO analysis of the crystal geometries revealed that the strength of these interactions ranging from 0.14 to 5.67 kcal.mol−1. We have also demonstrated that the N-substituted thiones have excellent reactive oxygen species (ROS) scavenging property and, thus, protect biomolecules including DNA and protein against Cu(I)-mediated oxidative damage.

Molecular structure, interactions, and antimicrobial properties of curcumin-PLGA Complexes-a DFT study.

Density functional calculations are performed to study the molecular structure, interactions, and antimicrobial activity of curcumin-poly lacto glycolic acid (Cur-PLGA) complexes. The calculations are performed on curcumin (Cur), glycolic acid (SSC and AAT conformers), lactic acid (LA), Cur-SSC, Cur-AAT, Cur-LA, and Cur-PLGA complexes using dispersion corrected M06-2X functional with 6-31 + G* basis set. The condensed Fukui functions of Cur are calculated to identify the favorable reactive sites. Inter- and intramolecular H-bond interactions are analyzed in detail through natural bond orbital, Atoms in Molecule, and Reduced density gradient analyses. The interaction energy values indicate that the interaction between Cur and AAT is stronger than the other studied complexes. Further, our calculations show that the PLGA interacted with Cur is having lower LUMO energy and density values. This indicates that the antimicrobial activity is high in this complex.

Intramolecular Hydrogen-Bond Interactions Tune Reactivity in Biomimetic Bis(μ-hydroxo)dicobalt Complexes.

Active site hydrogen-bond (H-bond) networks represent a key component by which metalloenzymes control the formation and deployment of high-valent transition metal-oxo intermediates. We report a series of dinuclear cobalt complexes that serve as structural models for the nonheme diiron enzyme family and feature a Co2(μ-OH)2 diamond core stabilized by intramolecular H-bond interactions. We define the conditions required for the kinetically controlled synthesis of these complexes: [Co2(μ-OH)2(μ-OAc)(κ1-OAc)2(pyR)4][PF6] (1R), where OAc = acetate and pyR = pyridine with para-substituent R, and we describe a homologous series of 1R in which the para-R substituent on pyridine is modulated. The solid state X-ray diffraction (XRD) structures of 1R are similar across the series, but in solution, their 1H NMR spectra reveal a linear free energy relationship (LFER) where, as R becomes increasingly electron-withdrawing, the intramolecular H-bond interaction between bridging μ-OH and κ1-acetate ligands results in increasingly "oxo-like" μ-OH bridges. Deprotonation of the bridging μ-OH results in the quantitative conversion to corresponding cubane complexes: [Co4(μ-O)4(μ3-OAc)4(pyR)4] (2R), which represent the thermodynamic sink of self-assembly. These reactions are unusually slow for rate-limiting deprotonation events, but rapid-mixing experiments reveal a 6000-fold rate acceleration on going from R = OMe to R = CN. These results suggest that we can tune reactivity by modulating the μ-OH pKa in the presence of intramolecular H-bond interactions to maintain stability as the octahedral d6 centers become increasingly acidic. Nature may similarly employ dynamic carboxylate-mediated H-bond interactions to control the reactivity of acidic transition metal-oxo intermediates.

Lithiated Calix[n]arenes (n = 6 or 8): Synthesis, Structures, and Use in the Ring-Opening Polymerization of Cyclic Esters.

A variety of lithiated calix[n]arenes, for which n = 6 or 8, have been isolated, structurally characterized, and evaluated as catalysts for the ring-opening polymerization (ROP) of the cyclic esters ε-caprolactone (ε-CL), δ-valerolactone (δ-VL), and rac-lactide (r-LA). In particular, interaction of p-tert-butylcalix[6]areneH6 (L6H6) with LiOtBu in THF led to the isolation of [Li14(L6H)2(CO3)2(THF)6(OH2)6]·14THF (1·14THF), the core of which has a chain of five Li2O2 diamonds. Similar use of p-tert-butylcalix[8]areneH8 (L8H8) afforded [Li10(L8)(OH)2(THF)8]·7THF (2·7THF), where the core is composed of a six-rung Li-O ladder. Use of debutylated calix[8]areneH8 (deBuL8H8) led to an elongated dimer [Li18(deBuL8)2(OtBu)2(THF)14]·4THF (3·4THF) in which the calix[8]arenes possess a wavelike conformation forming bridges to link three separate LixOy clusters (where x and y = 6, ignoring the THF donor oxygens). Interaction of L8H8 with LiOH·H2O afforded [Li4(L8H4)(OH2)4(THF)6]·5.5THF (4·5.5THF), where intramolecular H-bond interactions involving Li, O, and H construct a cage in the core of the structure with six- and eight-membered rings. Lastly, addition of Me3Al to the solution generated from L8H8 and LiOtBu led to the isolation of [(AlMe2)2Li20(L8H2)2(OH2)4(O2-)4(OH)2(NCMe)12]·10MeCN (5·10MeCN) in which Li, O, Al, and N centers build a polyhedral core. These complexes have been screened for their potential to act as precatalysts in the ring-opening polymerization (ROP) of ε-CL, δ-VL, and r-LA. For the ROP of ε-CL, δ-VL, and r-LA, systems 1-4 exhibited moderate activity at 130 °C over 8 h. In the case of ROP using the mixed-metal (Li/Al) system 5, better conversions and high molecular weight polymers were achieved. In the case of the ROP of ω-pentadecalactone (ω-PDL), the systems proved to be inactive under the conditions employed herein.

Exploring H-bonding interaction to enhance proton permeability of an acid-selective membrane

Acid recovery from industrial aqueous streams is an essential process, which commonly requires a cost-effective, energy-efficient, and straightforward approach, such as membrane technology. However, the limited acid/salt separation performance of the membrane materials makes the use of membrane technology very challenging. In this study, we fabricated acid-selective membranes by grafting urea groups and quaternary ammoniums (QA) containing side chains on the hydrophobic poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) backbones. As confirmed by Nano-scale microscopy and Small-angle X-ray scattering techniques, the intramolecular H-bonding interactions between urea units facilitate self-assembly of the side chains and the formation of continuous acid transport channels. The produced QA clusters also enabled fast anion transportation but reject cations transport, while the H-bonding networks provide a proton conduction pathway to endow high acid/salt selectivity. The resultant acid selective membranes showed a higher H+ dialysis coefficient (0.081 m h−1) and better selectivities for the separation of HCl from FeCl2 aqueous solution (31.1) than the recently reported commercial membranes. Moreover, ten consecutive cycles of acid recovery tests demonstrated excellent operational stability of the representative membrane.

Synthesis, characterization and catalytic activity of a mononuclear nonheme copper(II)-iodosylbenzene adduct

Iodosylbenzene (PhIO) and its derivatives have attracted significant attention due to their various applications in organic synthesis and biomimetic studies. For example, PhIO has been extensively used for generating high-valent metal-oxo species that have been regarded as key intermediates in diverse oxidative reactions in biological system. However, recent studies have shown that metal-iodosylbenzene adduct, known as a precursor of metal-oxo species, plays an important role in transition metal-catalyzed oxidation reactions. During last few decades, extensive investigations have been conducted on the synthesis and reactivity studies of metal-iodosylbenzene adducts with early and middle transition metals including manganese, iron, cobalt. Nevertheless, metal-iodosylbenzene adducts with late transition metals such as nickel, copper and zinc, still remains elusive. Herein, we report a novel copper(II)-iodosylbenzene adduct bearing a linear ligand composed of two pyridine rings and an ethoxyethanol side-chain, [Cu(OIPh)(HN3O2)]2+ (1). The copper(II)-iodosylbenzene adduct was characterized by several spectroscopic methods including UV–vis spectroscopy, electrospray ionization mass spectrometer (ESI MS), and electron paramagnetic resonance (EPR) combined with theoretical calculations. Interestingly, 1 can carry out the catalytic sulfoxidation reaction. In sulfoxidation reaction with thioanisole under catalytic reaction condition, not only two-electron but also four-electron oxidized products such sulfoxide and sulfone were yielded, respectively. However, 1 was not an efficient oxidant towards CH bond activation and epoxidation reactions due to the steric hindrance created by the intramolecular H-bonding interaction between HN3O2 ligand and iodosylbenzene moiety.

Generation of an Elusive Permanent Merocyanine via a Unique Mechanochemical Reaction Pathway.

We report the discovery of a 2H-naphtho[1,2-b]pyran mechanophore that produces a permanent merocyanine dye upon mechanochemical activation, in contrast to the reversible product generated photochemically. Experiments suggest that the irreversibility of the mechanically generated merocyanine is due to a unique reaction in which the scission of an ester C-O bond reveals a β-hydroxy ketone that locks the merocyanine through an intramolecular H-bonding interaction. In addition to demonstrating the reactivity using solution-phase ultrasonication, permanent merocyanine generation is also achieved in solid polymeric materials. The permanent coloration achieved with the naphthopyran mechanophore affords unique opportunities for sensing and force-recording applications as well as fundamental studies limited by the reversibility of typical colorimetric force probes.

Small Molecule Activation with Intramolecular "Inverse" Frustrated Lewis Pairs.

The intramolecular "inverse" frustrated Lewis pairs (FLPs) of general formula 1-BR2 -2-[(Me2 N)2 C=N]-C6 H4 (3-6) [BR2 =BMes2 (3), BC12 H8 , (4), BBN (5), BBNO (6)] were synthesized and structurally characterized by multinuclear NMR spectroscopy and X-ray analysis. These novel types of pre-organized FLPs, featuring strongly basic guanidino units rigidly linked to weakly Lewis acidic boryl moieties via an ortho-phenylene linker, are capable of activating H-H, C-H, N-H, O-H, Si-H, B-H and C=O bonds. 4 and 5 deprotonated terminal alkynes and acetylene to form the zwitterionic borates 1-(RC≡C-BR2 )-2-[(Me2 N)2 C=NH]-C6 H4 (R=Ph, H) and reacted with ammonia, BnNH2 and pyrrolidine, to generate the FLP adducts 1-(R2 HN→BR2 )-2-[(Me2 N)2 C=NH]-C6 H4 , where the N-H functionality is activated by intramolecular H-bond interactions. In addition, 5 was found to rapidly add across the double bond of H2 CO, PhCHO and PhNCO to form cyclic zwitterionic guanidinium borates in excellent yields. Likewise, 5 is capable of cleaving H2 , HBPin and PhSiH3 to form various amino boranes. Collectively, the results demonstrate that these new types of intramolecular FLPs featuring weakly Lewis acidic boryl and strongly basic guanidino moieties are as potent as conventional intramolecular FLPs with strongly Lewis acidic units in activating small molecules.

The subgroup of 2′-hydroxy-flavonoids: Molecular diversity, mechanism of action, and anticancer properties

Flavonoids are abundant in nature, structurally very diversified and largely investigated. However, the subgroup of 2′-hydroxyflavonoids is much less known and not frequently studied. The present review identifies the major naturally-occurring and synthetic 2′-hydroxyflavonoid derivatives and discusses their structural characteristics and biological properties, with a focus on anticancer activities. The pharmacological properties of 2′-hydroxyflavone (2′-HF) and 2′-hydroxyflavanone (2′-HFa) are detailed. Upon binding to the Ral-interacting protein Rlip implicated in the transport of glutathione conjugates, 2′-HFa inhibits tumor cell proliferation and restrict tumor growth, in particular in breast cancer models. Among the synthetic derivatives, the characteristics of the anticancer product 2D08 (2′,3′,4′-trihydroxy flavone) are detailed to shed light on the molecular mechanism of action of this compound, as a regulator of protein SUMOylation. Inhibition of protein SUMOylation by 2D08 blocks cancer cell migration and invasion, and the compound greatly enhances the anticancer effects of conventional cytotoxic drugs like etoposide. The structural role of the 2′-hydroxyl group on the phenyl C-ring of the flavonoid is discussed, notably the capacity to engage intramolecular H-bonding interactions with the O1 atom on the B-ring of the chromone unit (or the oxygen of a 3-OH group when it is presents). The 2′-hydroxyl group of flavonoid appears as a regulator of the conformational freedom between the bicyclic A-B unit and the appended phenyl C-ring, favoring the planarity of the molecule. It is an essential group accounting for the biological properties of 2′-HF, 2′-HFa and structurally related compounds. This review shed light on 2′-hydroxyflavonoids to encourage their use and chemical development.