Inés Corral

Competing ultrafast intersystem crossing and internal conversion: a time resolved picture for the deactivation of 6-thioguanine

In this paper we simulate the deactivation dynamics of photoexcited 6-thioguanine, a cytotoxic analogue of the canonical DNA/RNA base guanine, using a direct surface hopping dynamics approach. Our aim is to investigate the mechanism for triplet population, which was found to take place on a similar time scale as internal conversion. The surface hopping calculations were based on potential energy surfaces and couplings obtained on the fly using a semiempirical Hamiltonian, reparameterized on accurate ab initio data. We show that for the full description of the deactivation dynamics of 6-thioguanine, it is important to take into account both the dynamic and the spin–orbit couplings. The main deactivation pathway involves the sequence of ultrafast radiationless transitions S2 → S1 → T2 → T1. The very efficient population and long lifetime of the final T1 state, from where singlet oxygen is generated, would explain the high phototoxicity of the nucleotides of 6-thioguanine in DNA. To our knowledge, this is the first nonadiabatic dynamics simulation for a system showing strong spin–orbit couplings (due to the presence of a third row atom, sulfur) and a complex pattern of intermultiplet crossings.

The origin of efficient triplet state population in sulfur-substituted nucleobases

Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.

Electronic and Structural Elements That Regulate the Excited-State Dynamics in Purine Nucleobase Derivatives

The excited-state dynamics of the purine free base and 9-methylpurine are investigated using experimental and theoretical methods. Femtosecond broadband transient absorption experiments reveal that excitation of these purine derivatives in aqueous solution at 266 nm results primarily in ultrafast conversion of the S2(ππ*) state to the vibrationally excited 1nπ* state. Following vibrational and conformational relaxation, the 1nπ* state acts as a doorway state in the efficient population of the triplet manifold with an intersystem crossing lifetime of hundreds of picoseconds. Experiments show an almost 2-fold increase in the intersystem crossing rate on going from polar aprotic to nonpolar solvents, suggesting that a solvent-dependent energy barrier must be surmounted to access the singlet-to-triplet crossing region. Ab initio static and surface-hopping dynamics simulations lend strong support to the proposed relaxation mechanism. Collectively, the experimental and computational results demonstrate that the accessibility of the nπ* states and the topology of the potential energy surfaces in the vicinity of conical intersections are key elements in controlling the excited-state dynamics of the purine derivatives. From a structural perspective, it is shown that the purine chromophore is not responsible for the ultrafast internal conversion in the adenine and guanine monomers. Instead, C6 functionalization plays an important role in regulating the rates of radiative and nonradiative relaxation. C6 functionalization inhibits access to the 1nπ* state while simultaneously facilitating access to the 1ππ*(La)/S0 conical intersection, such that population of the 1nπ* state cannot compete with the relaxation pathways to the ground state involving ring puckering at the C2 position.

Electronic States of o-Nitrobenzaldehyde: A Combined Experimental and Theoretical Study

The experimental UV/vis absorption spectrum of ortho-nitrobenzaldehyde (o-NBA) has been assigned by means of MS-CASPT2/CASSCF, TD-DFT, and RI-CC2 theoretical computations. Additional information on the nature of the absorbing bands was obtained by comparing the o-NBA spectrum with that of related compounds, as, e.g., nitrobenzene and benzaldehyde. For wavelengths larger than approximately 280 nm, the absorption spectrum of o-NBA is dominated by a series of weak n pi* absorptions from the NO2 and CHO groups. These weak transitions are followed in energy by a more intense band, peaking at 250 nm and arising from charge transfer pi pi* excitations involving mainly benzene and nitro orbitals. Finally, the most intense band centered at 220 nm has its origin in the overlap of two different absorptions: the first one localized in the NO2 substituent and the second one arising from a charge transfer excitation involving the NO2 and the CHO fragments, respectively.

An Insight into the Mechanism of the Axial Ligand Exchange Reaction in Boron Subphthalocyanine Macrocycles

We provide here an insight into the mechanism of the axial ligand exchange reaction between chlorosubphthalocyanines and phenols. Our combined experimental and theoretical results support a bimolecular σ-bond metathesis mechanism in which the phenolic proton assists in weakening the boron-halogen bond concomitantly with substitution at the boron center. Such a reaction pathway, which is unusual in boron chemistry, is a consequence of the crowded and rigid chemical environment of the boron atom in these macrocycles. Furthermore, this work sheds light on the influence of different experimental parameters on the kinetics and efficiency of the most important reaction in subphthalocyanine chemistry.

Annulated Dinuclear Metal-Free and Zn(II) Phthalocyanines : Photophysical Studies and Quantum Mechanical Calculations

The results of steady-state and time-resolved absorption and fluorescence experiments as well as quantum mechanical density functional theory (DFT) calculations of metal-free and Zn(II) mononuclear and dinuclear (sharing a common benzene ring) phthalocyanines are presented. A detailed comparison between measured and calculated absorption spectra of all compounds is done, showing a good agreement between theory and experiment. The NH tautomerization for phthalocyanines with an extended pi-electron system was shown for the first time at room temperature. The photophysical properties of all possible NH tautomers of metal-free dinuclear Pc have been fully characterized. In the first tautomer, Pc(parallel), both pairs of hydrogen atoms are parallel to the connection line of two Pc units. The maximum of the lowest-energy Q absorption band, lambda abs, in Pc(parallel) is located at 832 nm, whereas the spectral position of the fluorescence maximum lies at lambdafl=837 nm. The second NH tautomer, Pc(perpendicular) (lambdaabs=853 nm, lambdafl=860 nm), presents the two pairs of hydrogen atoms perpendicularly orientated to the covalent axis, and the third one, Pc(mix) (lambdaabs=864 nm, lambdafl=872 nm), contributing in a minor extend to the absorption and fluorescence spectra of the metal-free dinuclear phthalocyanine, has one perpendicular and one parallel pair of hydrogen atoms. Obviously, only one configuration exists in the case of the Zn(II)-containing dinuclear phthalocyanine (lambdaabs=845 nm, lambdafl=852 nm).

Versatile Bottom-up Approach to Stapled π-Conjugated Helical Scaffolds: Synthesis and Chiroptical Properties of Cyclic o-Phenylene Ethynylene Oligomers†

Spring loaded: the smallest members of a family of carbon nanocoils (CNCs), adopting a fixed helical structure, have been synthesized by introduction of one or two staples in o-phenylene ethynylene oligomers. The chiroptical responses of the systems having enantiopure L-tartrate-derived staples confirmed the induced helicity. Theoretical studies suggest that these CNCs are pseudoelastic.

Decoding the Molecular Basis for the Population Mechanism of the Triplet Phototoxic Precursors in UVA Light-Activated Pyrimidine Anticancer Drugs

The photosensitization of DNA by thionucleosides is a promising photo-chemotherapeutic treatment option for a variety of malignancies. DNA metabolization of thionated prodrugs can lead to cell death upon exposure to a low dose of UVA light. The exact mechanisms of thionucleoside phototoxicity are still not fully understood. In this work, we have combined femtosecond broadband transient absorption experiments with state-of-the-art molecular simulations to provide mechanistic insights into the ultrafast and efficient population of the triplet state in the UVA-activated pyrimidine anticancer drug 4-thiothymine. The triplet state is thought to act as a precursor to DNA lesions and the reactive oxygen species responsible for 4-thiothymine photocytotoxicity. The electronic-structure and mechanistic results presented in this contribution reveal key molecular design criteria that can assist in developing alternative chemotherapeutic agents that may overcome some of the primary deficiencies of classical photosensitizers.

Binding energies of Cu+ to saturated and α,β-unsaturated alkanes, silanes and germanes: The role of agostic interactions

Abstract The gas-phase interaction of H 3 CCH 2 XH 3 and H 2 CC(H)XH 3 (X=C, Si, Ge) with Cu + has been investigated through the use of high-level density functional theory methods. The structures of the corresponding Cu + -complexes were optimized at the B3LYP/6-311G(d,p) level of theory, while the final energies were obtained in single-point B3LYP/6-311+G(2df,2p) calculations. In all cases, the most stable complexes are stabilized through agostic interactions between the metal cation and the hydrogen atoms of the XH 3 group. Only for the unsaturated derivatives, the interaction with the CC double bond competes with these agostic interactions, although the π-complexes for Si and Ge derivatives are slightly less stable. Since these interactions increase with the hydride character of the hydrogen atoms involved, ethylsilane and ethylgermane are predicted to bind Cu + much more strongly than propane. Conversely, vinylsilane and vinylgermane are predicted to have slightly lower Cu + binding energies than propene. These agostic interactions lead to a significant weakening of the XH linkages involved, reflected in a very large red shifting of the XH stretching frequency. A topological analysis of the charge density of these complexes seems to be a powerful tool to detect and characterize these agostic bonds. Actually, we have found a good correlation between the charge density at the agostic bond critical point and the stability of the complex.

The importance of agostic-type interactions for the binding energies of Ni+ to saturated and α,β-unsaturated alkanes, silanes and germanes

The gas-phase interaction of H3C–CH2–XH3 and H2CC(H)XH3 (X = C, Si, Ge) with Ni+ has been investigated through the use of high-level density functional theory methods. The structures of the corresponding Ni+ complexes were optimized at the B3LYP/6-311G(d,p) level of theory. Final energies were obtained in single-point B3LYP/6-311+G(2df,2p) calculations. In all cases, the most stable complexes are stabilized through agostic-type interactions between the metal cation and the hydrogen atoms of the XH3 group. Only for propene is the conventional π-complex the global minimum of the potential energy surface. These agostic-type linkages can be viewed as three-center bonds resulting from electron-donor interactions between σ bonding orbitals of the neutral and the empty s orbital of the metal and back-donation from pairs of valence electrons of the metal into the corresponding σ* antibonding orbitals of the neutral. As a consequence, these bonds are particularly stable for Si- and Ge-containing compounds, because of the high electron-donor ability of the XH3 group when the heteroatom is Si or Ge. Vinylsilane and vinylgermane lead to non-conventional complexes in which the metal bridges the Cα atom of the CC double bond and one of the hydrogen atoms of the XH3 group. In contrast with the behavior predicted when the reference acid is Cu+, Si- and Ge-derivatives, both saturated and unsaturated, bind Ni+ more strongly than propane and propene, respectively. Ni+ binding energies are systematically greater than Cu+ binding energies and the bond activation effects observed upon Ni+ attachment are sizably larger than those found upon Cu+ association.