Hydrogen bonding in the electronic excited state

Because of its fundamental importance in many branches of science, hydrogen bonding is a subject of intense contemporary research interest. The physical and chemical properties of hydrogen bonds in the ground state have been widely studied both experimentally and theoretically by chemists, physicists, and biologists. However, hydrogen bonding in the electronic excited state, which plays an important role in many photophysical processes and photochemical reactions, has scarcely been investigated. Upon electronic excitation of hydrogen-bonded systems by light, the hydrogen donor and acceptor molecules must reorganize in the electronic excited state because of the significant charge distribution difference between the different electronic states. The electronic excited-state hydrogen-bonding dynamics, which are predominantly determined by the vibrational motions of the hydrogen donor and acceptor groups, generally occur on ultrafast time scales of hundreds of femtoseconds. As a result, state-of-the-art femtosecond time-resolved vibrational spectroscopy is used to directly monitor the ultrafast dynamical behavior of hydrogen bonds in the electronic excited state. It is important to note that the excited-state hydrogen-bonding dynamics are coupled to the electronic excitation. Fortunately, the combination of femtosecond time-resolved spectroscopy and accurate quantum chemistry calculations of excited states resolves this issue in laser experiments. Through a comparison of the hydrogen-bonded complex to the separated hydrogen donor or acceptor in ground and electronic excited states, the excited-state hydrogen-bonding structure and dynamics have been obtained. Moreover, we have also demonstrated the importance of hydrogen bonding in many photophysical processes and photochemical reactions. In this Account, we review our recent advances in electronic excited-state hydrogen-bonding dynamics and the significant role of electronic excited-state hydrogen bonding on internal conversion (IC), electronic spectral shifts (ESS), photoinduced electron transfer (PET), fluorescence quenching (FQ), intramolecular charge transfer (ICT), and metal-to-ligand charge transfer (MLCT). The combination of various spectroscopic experiments with theoretical calculations has led to tremendous progress in excited-state hydrogen-bonding research. We first demonstrated that the intermolecular hydrogen bond in the electronic excited state is greatly strengthened for coumarin chromophores and weakened for thiocarbonyl chromophores. We have also clarified that the intermolecular hydrogen-bond strengthening and weakening correspond to red-shifts and blue-shifts, respectively, in the electronic spectra. Moreover, radiationless deactivations (via IC, PET, ICT, MLCT, and so on) can be dramatically influenced through the regulation of electronic states by hydrogen-bonding interactions. Consequently, the fluorescence of chromophores in hydrogen-bonded surroundings is quenched or enhanced by hydrogen bonds. Our research expands our understanding of the nature of hydrogen bonding by delineating the interaction between hydrogen bonds and photons, thereby providing a basis for excited-state hydrogen bonding studies in photophysics, photochemistry, and photobiology.     

Preparation and characterization of hydrogen-bonded P4VP-bisazobenzene complexes

Photoresponsive supramolecular complexes contain 4-hydroxyethyloxy-4??-(4-nitrophenylazo)azobenzene(BisAzo) molecule as a hydrogen bonding donor and poly(4-vinylpyridine) (P4VP) as a hydrogen bonding acceptor, and strong phenol pyridine hydrogen bonding is formed between them. FT-IR spectrum verifies the hydrogen bonding has formed between the phenol hydroxyl of BisAzo and pyridine ring of P4VP. The glass- transition temperature (Tg) is determined with differential-scanning calorimetry(DSC) and a decrease of complexes compared with pure P4VP is observed due to the attachment of BisAzo onto the backbone of P4VP. Polarized optical microscopy (POM) is performed to study the structure of supramolecular complexes,with a different texture observed which is different from both constituents alone. X-ray diffraction patterns are investigated with the same films already used for POM observation, indicating a lamellar structure with a periodic thickness of 4.1?nm. The supramolecular complexes P4VP/(BisAzo)_x are prepared with the molar ratio of BisAzo to the pyridine group varied at x?=?0.25, 0.5, 0.75 and 1.0, no mass aggregation is observed even at a high concentration of chromophore.     

Hydrogen-bonding-induced phenomena in bifunctional heteroazaaromatics

Ground and excited state processes induced by hydrogen bond formation are discussed for a family of heterocyclic compounds which possess both a proton donor (pyrrole NH group) and an acceptor (pyridine-type nitrogen). Excited state double proton transfer and rapid S(0) <-- S(1) internal conversion are observed only for molecules capable of forming cyclic, multiply hydrogen-bonded complexes. If the 1:1 cyclic, doubly hydrogen-bonded solvate is present in the ground state, the phototautomerization occurs even in rigid solvents at low temperatures. Internal conversion process requires solvent rearrangement and, therefore, does not proceed in a rigid environment. Another type of fluorescence quenching was also detected, involving photoinduced electron transfer from an excited chromophore to an aromatic hydrogen-bonded acceptor, such as pyridine. In molecules consisting of proton donor and acceptor units linked by a single bond, syn-anti rotamerization caused by hydrogen bonding is observed.     

A FRET-Based Near-Infrared Fluorescent Probe for Ratiometric Detection of Cysteine in Mitochondria

We report a near-infrared fluorescent probe A for the ratiometric detection of cysteine based on FRET from a coumarin donor to a near-infrared rhodamine acceptor. Upon addition of cysteine, the coumarin fluorescence increased dramatically up to 18-fold and the fluorescence of the rhodamine acceptor decreased moderately by 45 % under excitation of the coumarin unit. Probe A has been used to detect cysteine concentration changes in live cells ratiometrically and to visualize fluctuations in cysteine concentrations induced by oxidation stress through treatment with hydrogen peroxide or lipopolysaccharide (LPS). Finally, probe A was successfully applied for the in vivo imaging of Drosophila melanogaster larvae to measure cysteine concentration changes.     

Role of acid-base interfacial bonding in adhesion

The strength of macroscopic adhesive bonds of polymers is known to be directly proportional to the microscopic exothermic interfacial energy changes of bond formation, as measured by Dupre's 'work of adhesion'. Since the work of adhesion can be very appreciably increased by interfacial acid-base bonding with concomitant increases in adhesive bond strength, it is important to understand the acid-base character of polymers and of the surface sites of substrates or of the reinforcing fillers of polymer composites. The best known acid-base bonds are the hydrogen bonds; these are typical of acid-base bonds, with interaction energies dependent on the acidity of the hydrogen donor and on the basicity of the hydrogen acceptor. The strengths of the acidic or basic sites of polymers and of inorganic substrates can be easily determined by spectroscopic or calorimetric methods, and from this information one can start to predict the strengths of adhesive bonds. An important application of the new knowledge of interfacial acid-base bonding is the predictable enhancement of interfacial bonding accomplished by surface modification of inorganic surfaces to enhance the interfacial acid-base interactions.     

Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

Proposal of a New Method for Measuring F?rster Resonance Energy Transfer (FRET) Rapidly,Quantitatively and Non-Destructively

The process of radiationless energy transfer from a chromophore in an excited electronic state (the “donor”) to another chromophore (an “acceptor”), in which the energy released by the donor effects an electronic transition, is known as “Förster Resonance Energy Transfer” (FRET). The rate of energy transfer is dependent on the sixth power of the distance between donor and acceptor. Determining FRET efficiencies is tantamount to measuring distances between molecules. A new method is proposed for determining FRET efficiencies rapidly, quantitatively, and non-destructively on ensembles containing donor acceptor pairs: at wavelengths suitable for mutually exclusive excitations of donors and acceptors, two laser beams are intensity-modulated in rectangular patterns at duty cycle ½ and frequencies f₁ and f₂ by electro-optic modulators. In an ensemble exposed to these laser beams, the donor excitation is modulated at f₁, and the acceptor excitation, and therefore the degree of saturation of the excited electronic state of the acceptors, is modulated at f₂. Since the ensemble contains donor acceptor pairs engaged in FRET, the released donor fluorescence is modulated not only at f₁ but also at the beat frequency Δf: = |f₁ − f₂|. The depth of the latter modulation, detectable via a lock-in amplifier, quantitatively indicates the FRET efficiency.     

Spectroscopic study of solvent effects on the electronic absorption spectra of flavone and 7-hydroxyflavone in neat and binary solvent mixtures

The solvatochromic characteristics of flavone and 7-hydroxyflavone were investigated in neat and binary solvent mixtures. The spectral shifts of these solutes were correlated with the Kamlet and Taft parameters (α, β and π*) using linear solvation energy relationships. The multiparametric analysis indicates that both specific hydrogen bond donor ability and non-specific dipolar interactions of the solvents play an important role in absorption maxima of flavone in pure solvents. The hydrogen bond acceptor ability of the solvent was the main parameter affecting the absorption maxima of 7-hydroxyflavone. The simulated absorption spectra using a TD-DFT method were in good agreement with the experimental ones for both flavones. Index of preferential solvation was calculated as a function of solvent composition. Preferential solvation by ethanol was detected in cyclohexane-ethanol and acetonitrile-ethanol mixtures for flavone and in acetonitrile-ethanol mixtures for 7-hydroxyflavone. These results indicate that intermolecular hydrogen bonds between solute and solvent are responsible for the non-linear variation of the solvatochromic shifts on the mole fraction of ethanol in the analyzed binary mixtures.     

Sensitivity of Intra- and Intermolecular Interactions of Benzo[h]quinoline from Car–Parrinello Molecular Dynamics and Electronic Structure Inspection

The O-H...N and O-H...O hydrogen bonds were investigated in 10-hydroxybenzo[h]quinoline (HBQ) and benzo[h]quinoline-2-methylresorcinol complex in vacuo, solvent and crystalline phases. The chosen systems contain analogous donor and acceptor moieties but differently coupled (intra- versus intermolecularly). Car–Parrinello molecular dynamics (CPMD) was employed to shed light onto principle components of interactions responsible for the self-assembly. It was applied to study the dynamics of the hydrogen bonds and vibrational features as well as to provide initial geometries for incorporation of quantum effects and electronic structure studies. The vibrational features were revealed using Fourier transformation of the autocorrelation function of atomic velocity and by inclusion of nuclear quantum effects on the O-H stretching solving vibrational Schrödinger equation a posteriori. The potential of mean force (Pmf) was computed for the whole trajectory to derive the probability density distribution and for the O-H stretching mode from the proton vibrational eigenfunctions and eigenvalues incorporating statistical sampling and nuclear quantum effects. The electronic structure changes of the benzo[h]quinoline-2-methylresorcinol dimer and trimers were studied based on Constrained Density Functional Theory (CDFT) whereas the Electron Localization Function (ELF) method was applied for all systems. It was found that the bridged proton is localized on the donor side in both investigated systems in vacuo. The crystalline phase simulations indicated bridged proton-sharing and transfer events in HBQ. These effects are even more pronounced when nuclear quantization is taken into account, and the quantized Pmf allows the proton to sample the acceptor area more efficiently. The CDFT indicated the charge depletion at the bridged proton for the analyzed dimer and trimers in solvent. The ELF analysis showed the presence of the isolated proton (a signature of the strongest hydrogen bonds) only in some parts of the HBQ crystal simulation. The collected data underline the importance of the intramolecular coupling between the donor and acceptor moieties.     

Molecular Insight into the Self-Assembly Process of Cellulose Iβ Microfibril

The self-assembly process of β-D-glucose oligomers on the surface of cellulose Iβ microfibril involves crystallization, and this process is analyzed herein, in terms of the length and flexibility of the oligomer chain, by means of molecular dynamics (MD) simulations. The characterization of this process involves the structural relaxation of the oligomer, the recognition of the cellulose I microfibril, and the formation of several hydrogen bonds (HBs). This process is monitored on the basis of the changes in non-bonded energies and the interaction with hydrophilic and hydrophobic crystal faces. The oligomer length is considered a parameter for capturing insight into the energy landscape and its stability in the bound form with the cellulose I microfibril. We notice that the oligomer–microfibril complexes are more stable by increasing the number of hydrogen bond interactions, which is consistent with a gain in electrostatic energy. Our studies highlight the interaction with hydrophilic crystal planes on the microfibril and the acceptor role of the flexible oligomers in HB formation. In addition, we study by MD simulation the interaction between a protofibril and the cellulose I microfibril in solution. In this case, the main interaction consists of the formation of hydrogen bonds between hydrophilic faces, and those HBs involve donor groups in the protofibril.     

Molecular design and density functional theory investigation of novel low‐band‐gap benzobisthiadiazole‐based systems: from monomer to polymer

The electronic structure and properties of benzobisthiadiazole‐based alternating donor–acceptor conjugated oligomers and their periodic copolymers of donor and acceptor units with ratios of 1:1 and 2:1 were investigated systematically using the density functional theory method. The donors include thiophene, thieno[3,2‐b]thiophene and pyrrole. The ratio of donor to acceptor units (D:A ratio) plays a very important role in the geometric and electronic properties. The intramolecular charge transfer increases and the bond length alternation decreases with an increase in the D:A ratio for these oligomers and polymers. Moreover, an increase in D:A ratio can greatly reduce the band gap and effective mass of holes and electrons for these alternating donor‐acceptor conjugated copolymers. The unusually large intramolecular charge transfer caused by intramolecular hydrogen bonds reveals that pyrrole is not only a strong electron donor but also a potential hydrogen bond donor. The theoretical results suggest those copolymers possessing a D:A ratio of 2:1 are better candidates for conducting materials compared to those with a D:A ratio of 1:1. The almost zero band gap, large bandwidth and small effective mass of holes and electrons of poly(4,8‐bis(thieno[3,2‐b]thiophene‐2‐yl)benzo[1,2‐c:4,5‐c′]bis[1,2,5]thiadiazole) indicate that it is a very good candidate for an electrically conductive material. Copyright © 2010 Society of Chemical Industry     

Photoinduced Double Proton Transfer: Inter- and Intramolecular Cases

Photoinduced two-proton tautomerization has been studied in two types of chromophores: (i) alcohol complexes of azaaromatic molecules possessing both proton donor and acceptor groups; (ii) constitutional isomers of porphyrin. The reaction path for the intermolecular process may involve solvent reorientation around the excited chromophore. In this case, rapid internal conversion is activated, efficiently competing with proton transfer. Another possibility arises if cyclic, doubly-hydrogen-bonded complexes exist already in the ground state. Excitation of such species leads to a fast tautomerization, which is not stopped even at low temperatures. Excited-state double proton transfer also has been observed in cyclic dimers in the crystal phase. In porphyrin isomers, the rate of the process is a function of the strength of the intramolecular hydrogen bond. Dependence of the phototautomerization rate on temperature and on the nature of the surrounding matrix has also been studied.     

Ultrafast Energy Redistribution in Photoexcited Sodium-Ammonia Clusters

The dynamics in photoexcited Na(NH₃)_n clusters up to n = 20 using femtosecond laser pump and probe techniques are investigated. It is found that electronic excitation energy of the metal atom chromophore is transferred to internal vibrations of the surrounding ammonia solvent molecules. The transfer time strongly depends on the number of ammonia molecules bound to the sodium atom, decreasing from 2000 ps when only one ammonia molecules is attached to the metal atom down to a limiting value of about 100 fs for Na(NH₃)₁₀. These results can be understood in terms of an internal energy transfer where the rates are governed by the density of states and the Franck-Condon overlap of the acceptor modes.     

Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

Hydrogen bonds and salt bridges across protein-protein interfaces

To understand further, and to utilize, the interactions across protein- protein interfaces, we carried out an analysis of the hydrogen bonds and of the salt bridges in a collection of 319 non-redundant protein- protein interfaces derived from high-quality X-ray structures. We found that the geometry of the hydrogen bonds across protein interfaces is generally less optimal and has a wider distribution than typically observed within the chains. This difference originates from the more hydrophilic side chains buried in the binding interface than in the folded monomer interior. Protein folding differs from protein binding. Whereas in folding practically all degrees of freedom are available to the chain to attain its optimal configuration, this is not the case for rigid binding, where the protein molecules are already folded, with only six degrees of translational and rotational freedom available to the chains to achieve their most favorable bound configuration. These constraints enforce many polar/charged residues buried in the interface to form weak hydrogen bonds with protein atoms, rather than strongly hydrogen bonding to the solvent. Since interfacial hydrogen bonds are weaker than the intra-chain ones to compete with the binding of water, more water molecules are involved in bridging hydrogen bond networks across the protein interface than in the protein interior. Interfacial water molecules both mediate non-complementary donor-donor or acceptor- acceptor pairs, and connect non-optimally oriented donor-acceptor pairs. These differences between the interfacial hydrogen bonding patterns and the intra-chain ones further substantiate the notion that protein complexes formed by rigid binding may be far away from the global minimum conformations. Moreover, we summarize the pattern of charge complementarity and of the conservation of hydrogen bond network across binding interfaces. We further illustrate the utility of this study in understanding the specificity of protein-protein associations, and hence in docking prediction and molecular (inhibitor) design.      

Dynamics of water interacting with interfaces, molecules, and ions

Water is a critical component of many chemical processes, in fields as diverse as biology and geology. Water in chemical, biological, and other systems frequently occurs in very crowded situations: the confined water must interact with a variety of interfaces and molecular groups, often on a characteristic length scale of nanometers. Water's behavior in diverse environments is an important contributor to the functioning of chemical systems. In biology, water is found in cells, where it hydrates membranes and large biomolecules. In geology, interfacial water molecules can control ion adsorption and mineral dissolution. Embedded water molecules can change the structure of zeolites. In chemistry, water is an important polar solvent that is often in contact with interfaces, for example, in ion-exchange resin systems. Water is a very small molecule; its unusual properties for its size are attributable to the formation of extended hydrogen bond networks. A water molecule is similar in mass and volume to methane, but methane is a gas at room temperature, with melting and boiling points of 91 and 112 K, respectively. This is in contrast to water, with melting and boiling points of 273 and 373 K, respectively. The difference is that water forms up to four hydrogen bonds with approximately tetrahedral geometry. Water's hydrogen bond network is not static. Hydrogen bonds are constantly forming and breaking. In bulk water, the time scale for hydrogen bond randomization through concerted formation and dissociation of hydrogen bonds is approximately 2 ps. Water's rapid hydrogen bond rearrangement makes possible many of the processes that occur in water, such as protein folding and ion solvation. However, many processes involving water do not take place in pure bulk water, and water's hydrogen bond structural dynamics can be substantially influenced by the presence of, for example, interfaces, ions, and large molecules. In this Account, spectroscopic studies that have been used to explore the details of these influences are discussed. Because rearrangements of water molecules occur so quickly, ultrafast infrared experiments that probe water's hydroxyl stretching mode are useful in providing direct information about water dynamics on the appropriate time scales. Infrared polarization-selective pump-probe experiments and two-dimensional infrared (2D IR) vibrational echo experiments have been used to study the hydrogen bond dynamics of water. Water orientational relaxation, which requires hydrogen bond rearrangements, has been studied at spherical interfaces of ionic reverse micelles and compared with planar interfaces of lamellar structures composed of the same surfactants. Water orientational relaxation slows considerably at interfaces. It is found that the geometry of the interface is less important than the presence of the interface. The influence of ions is shown to slow hydrogen bond rearrangements. However, comparing an ionic interface to a neutral interface demonstrates that the chemical nature of the interface is less important than the presence of the interface. Finally, it is found that the dynamics of water at an organic interface is very similar to water molecules interacting with a large polyether.     

Subpicosecond solvent dynamics in charge-transfer transitions: challenges and opportunities in resonance Raman spectroscopy

Resonance Raman spectroscopy is an established tool for the determination of structure and dynamics in electronically excited states. In condensed-phase systems, Raman excitation profiles and electronic absorption spectra depend on changes in molecular geometry and solvation structure induced by electronic excitation. Recent studies of solvent isotope effects on resonance Raman intensities in charge-transfer excitations reveal solvent dynamics taking place on a subpicosecond time scale and vibrational mode-specific solute-solvent interactions. These discoveries present challenges to the current working theories for analysis of resonance Raman and absorption spectra.     

Hydrogen bond detachment in polymer complexes

The hydrogen bonded polymer complex bulk and thin film was prepared by solution mixing and layer-by-layer assembly, respectively. Poly(vinylpyrrolidone) (PVPON) and poly(ethylene oxide) (PEO) were hydrogen bonding acceptor polymers while poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) were hydrogen bonding donor polymers. The detachment of hydrogen bond between the chains in polymer complexes was investigated during the dissolution in alkaline solution, ionic liquid and tertiary amine N-oxide. We compared the dissolution process of the polymer complex bulk with the polymer complex thin film, and discussed the polymer chain length, chain entanglement degree and temperature effect on hydrogen bond detachment and dissolution of polymer complexes.     

Predicting the shape of organic crystals grown from polar solvents

A method for predicting the shape of organic crystals grown from polar solvents is presented. The model is an improvement of the recent method developed by Winn and Doherty (A.I.Ch.E. Journal 44 (1998) 2501) for predicting the shape of organic crystals grown from solvents in which the energy of adhesion at the interfaces is dominated by dispersive forces (e.g., non-polar solvents). The principal characteristic of the new method is that it can account for the role of hydrogen donor and hydrogen acceptor atoms in forming strong bonds at the interface. This technique is a first step towards predicting the shapes of organic crystals grown from polar solvents, and has been applied successfully to predict the shape of adipic acid grown from water, and succinic acid grown from water and from propanol.     

A fluorescence resonance energy transfer probe for sensing pH in aqueous solution

A fluorescence resonance energy transfer (FRET) sensor, which has a FRET donor and an acceptor attached to each chain end of pH-sensitive polysulfonamide, is synthesized and its pH sensitivity is examined in terms of the FRET efficiency. This polymeric sensor exhibits an instantaneous conformation change from coil to globule at a specific pH, which results in the drastic on-and-off FRET efficiency. To detect a specific pH region, sulfadimethoxine and sulfamethizole are selected among various sulfonamides since their pK_a values are in the physiological pH. For tuning the emission color arising from FRET, 7-hydroxy-4-bromomethyl coumarin and coumarin 343 are used as a FRET donor and an acceptor, respectively, for a blue-to-green FRET sensor, and fluorescence amine isomer I and rhodamine B are used for a green-to-red FRET sensor. Each sensor shows a distinct color change from the emission wavelength of FRET donor to the emission wavelength of FRET acceptor, which well explains their feasibility as a useful optical sensor.