Mechanistic DFT Study of 1,3-Dipolar Cycloadditions of Azides with Guanidine.

Density functional calculations SMD(chloroform)//B3LYP/6-311+G(2d,p) were employed in the computational study of 1,3-dipolar cycloadditions of azides with guanidine. The formation of two regioisomeric tetrazoles and their rearrangement to cyclic aziridines and open-chain guanidine products were modeled. The results suggest the feasibility of an uncatalyzed reaction under very drastic conditions since the thermodynamically preferred reaction path (a), which involves cycloaddition by binding the carbon atom from guanidine to the terminal azide nitrogen atom, and the guanidine imino nitrogen with the inner N atom from the azide, has an energy barrier higher than 50 kcal mol-1. The formation of the other regioisomeric tetrazole (imino nitrogen interacts with terminal N atom of azide) in direction (b) can be more favorable and proceed under milder conditions if alternative activation of the nitrogen molecule releases (e.g., photochemical activation), or deamination could be achieved because these processes have the highest barrier in the less favorable (b) branch of the mechanism. The introduction of substituents should favorably affect the cycloaddition reactivity of the azides, with the greatest effects expected for the benzyl and perfluorophenyl groups.

Wavelength dependent photochemistry of BODIPY-phenols and their applications in the fluorescent labeling of proteins.

A series of BODIPY dyes were synthesized, that were at the 3, or 3 and 5 positions, substituted by photochemically reactive quinone methide (QM) precursor moieties. Fluorescence properties of the molecules were investigated and we demonstrated that the molecules undergo wavelength dependent photochemistry. Photodeamination to deliver QMs takes place only upon excitation to higher excited singlet states, showing unusual anti-Kasha photochemical reactivity. The findings were corroborated by TD-DFT computations. Laser flash photolysis experiments could not reveal QMs due to the low efficiency of their formation, but enabled the detection of phenoxyl radicals. The applicability of the molecules for the fluorescent labeling of bovine serum albumin as a model protein upon photoexcitation at 350 nm was demonstrated.

SOMO-HOMO Conversion in Triplet Carbenes.

In this study, the SOMO-HOMO conversion has been shown for the first time in triplet carbenes embedded in cycloparaphenylene units. The high-lying HOMO originating from the curved π-conjugated system and the low-lying SOMO-1 originating due to the small carbene angle are the key to endowing this interesting electronic configuration. Furthermore, simple planar triplet carbenes such as fluorenylidene were found to possess SOMO-HOMO energy-converted electronic configurations.

1,3-Diradicals Embedded in Curved Paraphenylene Units: Singlet versus Triplet State and In-Plane Aromaticity.

Curved π-conjugated molecules and open-shell structures have attracted much attention from the perspective of fundamental chemistry, as well as materials science. In this study, the chemistry of 1,3-diradicals (DRs) embedded in curved cycloparaphenylene (CPPs) structures, DR-(n+3)CPPs (n = 0-5), was investigated to understand the effects of the curvature and system size on the spin-spin interactions and singlet versus triplet state, as well as their unique characteristics such as in-plane aromaticity. A triplet ground state was predicted for the larger 1,3-diradicals, such as the seven- and eight-paraphenylene-unit-containing diradicals DR-7CPP (n = 4) and DR-8CPP (n = 5), by quantum chemical calculations. The smaller-sized diradicals DR-(n+3)CPPs (n = 0-3) were found to possess singlet ground states. Thus, the ground-state spin multiplicity is controlled by the size of the paraphenylene cycle. The size effect on the ground-state spin multiplicity was confirmed by the experimental generation of DR-6CPP in the photochemical denitrogenation of its azo-containing precursor (AZ-6CPP). Intriguingly, a unique type of in-plane aromaticity emerged in the smaller-sized singlet states such as S-DR-4CPP (n = 1), as proven by nucleus-independent chemical shift calculations (NICS) and an analysis of the anisotropy of the induced current density (ACID), which demonstrate that homoconjugation between the 1,3-diradical moiety arises because of the curved and distorted bonding system.

Labeling of Proteins by BODIPY-Quinone Methides Utilizing Anti-Kasha Photochemistry.

A novel approach for the photolabeling of proteins by a BODIPY fluorophore is reported that is based on an anti-Kasha photochemical reaction from an upper singlet excited state (Sn) leading to the deamination of the BODIPY quinone methide precursor. On the other hand, the high photochemical stability of the dye upon excitation by visible light to S1 allows for the selective fluorescence detection from the dye or dye-protein adduct, without concomitant bleaching or hydrolysis of the protein-dye adduct. Therefore, photolabeling and fluorescence monitoring can be uncoupled by using different excitation wavelengths. Combined theoretical and experimental studies by preparative irradiations, fluorescence, and laser flash photolysis fully disclose the photophysical properties of the dye and its anti-Kasha photochemical reactivity. The application of the dye was demonstrated on photolabeling of bovine serum albumin.

Curve Effect on Singlet Diradical Contribution in Kekulé-type Diradicals: A Sensitive Probe for Quinoidal Structure in Curved π-Conjugated Molecules.

Curved (non-planar) aromatic compounds have attracted significant research attention in the fields of basic chemistry and materials science. The contribution of the quinoidal structure in the curved π-conjugated structures has been proposed to be the key for materials functions. In this study, the curve effect on the quinoidal contribution was investigated in Kekulé-type singlet diradicals (S-DR1-4) as a sensitive probe for quinoidal structures in curved π-conjugated molecules. The quinoidal contribution in S-DR1-4 was found to increase with increasing the curvature of the curved structure, which was quantitatively analyzed using NBO analysis and the natural orbital occupation numbers computed by the CASSCF method. The curve effect on the singlet-triplet energy gap was examined by the CASPT2 method. The singlet-triplet energy gaps for the highly π-conjugated diradicals were determined for the first time using the CASPT2 method. Substantial quinoidal contribution was found in the curved structures of the delocalized singlet diradicals S-DR1-4, in contrast to its absence in the corresponding triplet states T-DR1-4.

Ultrafast Adiabatic Photodehydration of 2-Hydroxymethylphenol and the Formation of Quinone Methide.

The photochemical reactivity of 2-hydroxymethylphenol (1) was investigated experimentally by photochemistry under cryogenic conditions, by detecting reactive intermediates by IR spectroscopy, and by using nanosecond and femtosecond transient absorption spectroscopic methods in solution at room temperature. In addition, theoretical studies were performed to facilitate the interpretation of the experimental results and also to simulate the reaction pathway to obtain a better understanding of the reaction mechanism. The main finding of this work is that photodehydration of 1 takes place in an ultrafast adiabatic photochemical reaction without any clear intermediate, delivering quinone methide (QM) in the excited state. Upon photoexcitation to a higher vibrational level of the singlet excited state, 1 undergoes vibrational relaxation leading to two photochemical pathways, one by which synchronous elimination of H2 O gives QM 2 in its S1 state and the other by which homolytic cleavage of the phenolic O-H bond produces a phenoxyl radical (S0 ). Both are ultrafast processes that occur within a picosecond. The excited state of QM 2 (S1 ) probably deactivates to S0 through a conical intersection to give QM 2 (S0 ), which subsequently delivers benzoxete 4. Elucidation of the reaction mechanisms for the photodehydration of phenols by which QMs are formed is important to tune the reactivity of QMs with DNA and proteins for the potential application of QMs in medicine as therapeutic agents.

Benzoylguanidines as Anion-Responsive Systems.

A series of benzoylguanidinium salts was prepared and the changes in UV/Vis spectra, triggered by the presence of anions, were investigated. All compounds undergo deprotonation with basic anions like dihydrogenphosphate and acetate in acetonitrile. The most pronounced spectral changes were obtained by deprotonation of N1 -benzoyl-N3 -(p-nitrophenyl) guanidinium chloride which shows the naked-eye visible color change from colorless to yellow. Measured pKa (BH+ ) in acetonitrile ranges from 12-16, which is comparable to the pyridinium cations. The proton transfer equilibria were also tested in acetonitrile/water mixture where all but the most acidic derivatives showed pKa (BH+ ) of 4-6 units which corresponds to apparent association constants of 104 -106  dm3 mol-1 . UV/Vis spectra of neutral and protonated forms were modelled by the TD-DFT approach using CAM-B3LYP and PBE0 functionals and compared to CC2 results. In the case of CAM-B3LYP, a parameter ω, defining amount of long-range exchange correction, was varied to achieve the best agreement with the experimental spectra. The optimized ω parameters are 0.10 a0 -1 for neutral benzoylguanidines and 0.20 a0 -1 for neutral nitrobenzoyl and protonated systems. The larger ω parameter in the latter is ascribed to more pronounced charge transfer character of the HOMO-LUMO transition - the one responsible for the lowest energy absorption band.

Hydroxymethylaniline Photocages for Carboxylic Acids and Alcohols.

ortho-, meta- and para-Hydroxymethylaniline methyl ethers 3-5-OMe and acetyl derivatives 3-5-OAc were investigated as potential photocages for alcohols and carboxylic acids, respectively. The measurements of photohydrolysis efficiency showed that the decaging from ortho- and meta-derivatives takes place efficiently in aqueous solution, but not for the para-derivatives. Contrary to previous reports, we show that the meta-derivatives are better photocages for alcohols, whereas ortho-derivatives are better protective groups for carboxylic acids. The observed differences were fully disclosed by mechanistic studies involving fluorescence measurements and laser flash photolysis (LFP). Photoheterolysis for the para-derivatives does not take place, whereas both meta- and ortho-derivatives undergo heterolysis and afford the corresponding carbocations 3-C and 4-C. The ortho-carbocation 4-o-C was detected by LFP in aqueous solution (λmax = 410 nm, τ ≈ 90 µs). Moreover, spectroscopic measurements for the meta-acetyl derivative 3-m-OAC indicated the formation of cation in the excited state. The application of an ortho-aniline derivative as a protective group was demonstrated by synthesizing several derivatives of carboxylic acids. In all cases, the photochemical deprotection was accomplished in high yields (>80%). This mechanistic study fully rationalized the photochemistry of aniline photocages which is important for the design of new photocages and has potential for synthetic, biological, and medicinal applications.

Insights on the Auxochromic Properties of the Guanidinium Group.

UV/vis spectra of phenylguanidine (PHGU) in the gas phase and in acetonitrile have been simulated by TD-DFT calculations. Several DFT hybrid and long-range corrected functionals were tested with respect to CASPT2 gas phase calculations. Solvent effects were considered using polarizable continuum model (PCM) and compared with the measured data in acetonitrile. Comparison with isoelectronic phenylurea and related phenyltiourea was done as well. The PBE0 and long-range corrected CAM-B3LYP functionals were selected to investigate the effect of protonation on the excitation energies and absorption intensities of PHGU and several guanidine derivatives with different aromatic chromophoric groups (naphthyl, anthracenyl, quinolinyl, anthraquinonyl, and coumarinyl). Also, the effect of complexation and specific interactions through hydrogen bonds with different anions was examined. It was shown that the protonation of the guanidine subunit shifts the low energy absorption bands toward higher energies (hypsochromic shift). The shift is reduced upon complexation with anions. In phenylguanidine salts, λmax values are correlated to the anion basicity and strength of H-bonding. The observed changes diminish upon increase of chromophoric size (naphthyl, anthracenyl). Theoretical predictions of UV/vis spectra correlate well with experimentally measured spectra of selected guanidine derivatives and their salts.

Reactivity of Cations and Zwitterions Formed in Photochemical and Acid-Catalyzed Reactions from m-Hydroxycycloalkyl-Substituted Phenol Derivatives.

Three m-substituted phenol derivatives, each with a labile benzylic alcohol group and bearing either protoadamantyl 4, homoadamantyl 5, or a cyclohexyl group 6, were synthesized and their thermal acid-catalyzed and photochemical solvolytic reactivity studied, using preparative irradiations, fluorescence measurements, nanosecond laser flash photolysis, and quantum chemical calculations. The choice of m-hydroxy-substitution was driven by the potential for these phenolic systems to generate m-quinone methides on photolysis, which could ultimately drive the excited-state pathway, as opposed to forming simple benzylic carbocations in the corresponding thermal route. Indeed, thermal acid-catalyzed reactions gave the corresponding cations, which undergo rearrangement and elimination from 4, only elimination from 5, and substitution and elimination from 6. On the other hand, upon photoexcitation of 4-6 to S1 in a polar protic solvent, proton dissociation from the phenol, coupled with elimination of the benzylic OH (as hydroxide ion) gave zwitterions (formal m-quinone methides). The zwitterions exhibit reactivity different from the corresponding cations due to a difference in charge distribution, as shown by DFT calculations. Thus, protoadamantyl zwitterion has a less nonclassical character than the corresponding cation, so it does not undergo 1,2-shift of the carbon atom, as observed in the acid-catalyzed reaction.

Photoinduced Intramolecular formal [4 + 2] Cycloaddition of Aryl-Substituted o-Vinylstyryl-2-oxazoles To Form Benzo[f]quinoline Derivatives: Experimental Results and Theoretical Interpretation.

A new approach to benzo[f]quinoline derivatives has been found by an effective formal [4 + 2] photocycloaddition process from novel aryl-substituted o-vinylstyryl-2-oxazoles. All of the o-vinylstyryl-2-oxazoles were synthesized by a multicomponent Wittig reaction from the diphosphonium salt of α,α'-o-xylene dibromide, formaldehyde, and 5-tolyl-, 4-phenyl-5-methyl-, and 4,5-diphenyloxazole-2-carbaldehydes. TD-DFT calculations revealed that the intramolecular photocyclization in 2-(2-vinylstyryl)oxazoles to form benzo[f]quinoline derivatives proceeds on the S1 PES via a stepwise pathway, namely by 10π followed by 6π ring closure. On that path the existence of an S0/S1 conical intersection was indicated. The reactivity of the photocyclization steps depends on the substitution pattern at positions 4 and 5 of the oxazole ring, where the aryl group in position 5 deactivates the reaction.

Guanidine and guanidinium cation in the excited state--theoretical investigation.

Diverse ab initio and density-functional-theory methods were used to investigate geometries, energies, and electronic absorption spectra of guanidine and its protonated form, as well as their photo-deactivation processes. It was shown that the guanidine is a weakly absorbing species with the excitation spectrum consisting mostly of transitions to the Rydberg excited states and one valence n-π4 state. The lowest energy band has a maximum at ca. 6.9 eV (∼180 nm). The protonation of guanidine affects its excitation spectrum substantially. A major shift of the Rydberg states to higher energies is clearly visible and strongly absorbing transitions from the ground state to the π3-π4 and π2-π4 states appears at 7.8 eV (∼160 nm). Three low-lying conical intersections (two for guanidine and one for protonated guanidine) between the ground state and the first excited singlet state were located. They are accessible from the Franck-Condon region through amino N-H stretching and out-of-plane deformations in guanidine and protonated guanidine, respectively. The relaxation of the π3-3s Rydberg state via amino N-H bond stretching was hindered by a barrier. The nondissociated conical intersection in protonated guanidine mediates the radiationless deactivation of the compound after excitation into the π3-π4 state. This fact is detrimental for the photostability of guanidine, since its conjugate acid is stable in aqueous solution over a wide pH range and in protein environment, where guanidinium moiety in arginine is expected to be in a protonated form.

Photodeactivation paths in norbornadiene.

The first high level ab initio quantum-chemical calculations of potential energy surfaces (PESs) for low-lying singlet excited states of norbornadiene in the gas phase are presented. The optimization of the stationary points (minima and conical intersections) and the recalculation of the energies were performed using the multireference configuration interaction with singles (MR-CIS) and the multiconfigurational second-order perturbation (CASPT2) methods, respectively. It was shown that the crossing between valence V2 and Rydberg R1 states close to the Franck-Condon (FC) point permits an easy population switch between these states. Also, a new deactivation path in which the doubly excited state with (π3)(2) configuration (DE) has a prominent role in photodeactivation from the R1 state due to the R1/DE and the DE/V1 conical intersections very close to the R1 and DE minima, respectively, was proposed. Subsequent deactivation from the V1 to the ground state goes through an Olivucci-Robb-type conical intersection that adopts a rhombic distorted geometry. The deactivation path has negligible barriers, thereby making ultrafast radiationless decay to the ground state possible.

QM/MM non-adiabatic decay dynamics of formamide in polar and non-polar solvents.

Non-adiabatic on-the-fly dynamics simulations of the photodynamics of formamide in water and n-hexane were performed using a QM/MM approach. It was shown that steric restrictions imposed by the solvent cage do not have an influence on the initial motion which leads to the lowest energy conical intersection seam. The initial deactivation in water is faster than in n-hexane and in the gas phase. However, most of the formamide molecules in water do not reach the ground state. The reason for the deactivation inefficiency in water is traced back to a decrease of close CO···HOH and NH···OH(2) contacts which fall in the range of hydrogen bonds. The energy deposition into H-bond breaking events leaves molecules with less energy for surmounting the CN dissociation barrier. In both solvents, after hopping to the ground state, the solvent cage keeps the HCO and NH(2) fragments or CO and NH(3) products in close proximity. Consequently, the number of trajectories where fast recombination happens is augmented with delayed recombinations that start when the dissociation fragments hit the cage wall and return back. The hot ground state formamide is formed in an internal conversion process identical to the path leading to CN photodissociation. In the case of aqueous formamide, good agreement with experimental results is achieved by combining dynamics simulations starting from the S(1) and the S(2) excited states collecting high and low energy trajectories, respectively.

Study of the mechanism of the N-CO photodissociation in N,N-dimethylformamide by direct trajectory surface hopping simulations.

Photodynamics of N,N-dimethylformamide (DMF) in its low-lying singlet excited n(O)-pi* and pi-pi* states have been explored by the direct trajectory surface hopping method based on multiconfigurational ab initio calculations. The dynamics simulations starting in the first excited singlet state (n(O)-pi*) showed that in 57% of trajectories, S(1) excited DMF decays to the ground via the crossing seam related to the N-CO bond stretching MXS1. In 41% of all trajectories, the relaxation process on the S(1) PES moves the molecule into the minimum, where it stays trapped until the end of simulation time. In simulations starting in the second excited state, all trajectories are found to deactivate through MXS5 (S(2)/S(1)) by very fast N-CO stretching. Because the N-CO dissociation process continues in the S(1) potential energy surface, most of the population overshoots the MXS1 and leads to fully dissociated electronically excited HCO and N(CH(3))(2) radicals. A mechanism for their deactivation by H-C-O and C-N-C bending modes is proposed.

Simulation of the photodeactivation of formamide in the nO-pi* and pi-pi* states: an ab initio on-the-fly surface-hopping dynamics study.

The short-time photodynamics (1 ps) of formamide in its low-lying singlet excited n(O)-pi(*) and pi-pi(*) states have been investigated by the direct trajectory surface-hopping method based on multiconfigurational ab initio calculations. The simulations showed that in both states, the primary deactivation process is C-N bond dissociation. In the ground state, the energy is transferred to (a) translational motion of the HCO and NH(2) fragments, (b) additional C-H dissociation from the vibrationally hot HCO fragment, or (c) formation of NH(3) and CO. In addition to the C-N dissociation pathway, C-O bond fission is found to be an additional primary deactivation path in the pi-pi(*) dynamics. From fractional occupations of trajectories, lifetimes of formamide were estimated: tau(S(1))=441 fs and tau(S(2))=66 fs.

On the bond-stretch isomerism in the benzo[1,2:4,5]dicyclobutadiene system--an ab initio MR-AQCC study.

Bond-stretch isomerism in benzo[1,2:4,5]dicyclobutadienle (BDCB) has been investigated using the MR-AQCC/6-31G(d) method, a high-level multireference ab initio approach including size-extensivity corrections. The applied theoretical approach includes both nondynamical and dynamical electron correlation effects. Full MR-AQCC geometry optimizations of localized (1) and delocalized (3) isomers as well as the transition structure (TS) have been determined using D2h, symmetry restriction. The calculations show that both isomers are approximately of equal stability separated by a barrier with a height of about 5 kcal mol(-1). Thus, the present results strongly indicate that benzof[1,3:4,5]dicyclobutadiene is a very good candidate for an organic compound exhibiting bond-stretch isomerism, since isomers 1 and 3 correspond to true minima on the double-well potential energy surface, which are separated by a sufficiently high barrier. It is particularly important to emphasize that isomer 3 represents a realization of the highly elusive quasi-[10]annulene.