G. Martins

The electronic states of pyrimidine studied by VUV photoabsorption and electron energy-loss spectroscopy

The electronic state spectroscopy of pyrimidine C(4)H(4)N(2) has been investigated using both high resolution VUV photoabsorption in the energy range 3.7 to 10.8 eV (335 to 115 nm) and lower resolution electron energy loss in the range 2 to 15 eV. The low energy absorption band, assigned to the (pi*) <-- 7b(2)(n(N)) (1(1)B(1)<-- 1(1)A(1)) transition, at 3.85(4) eV and the vibrational progressions superimposed upon it have been observed for the first time, due to the availability of a high-resolution photon beam (0.075 nm), corresponding to 3 meV at the midpoint of the energy range studied. Vibronic coupling has been shown to play an important role dictating the nature of the observed excited states, especially for the lowest (1)B(1) state. The 2(1)B(1) state is proposed to have its origin at 7.026 eV according to the vibrational excitation reported in this energy region (7.8-8.4 eV). New experimental evidence of 4(1)A(1) state with a maximum cross section at 8.800 eV is supported by previous ab initio quantum chemical calculations. Rydberg series have been assigned converging to the three lowest ionisation energy limits, 9.32 eV ((2)B(2)), 10.41 eV ((2)B(1)) and 11.1 eV ((2)A(1) + (2)A(2)) with new members reported for the first time and classified according to the magnitude of the quantum defects (delta). Additionally, the absolute differential cross section for inelastic electron scattering has been measured for the most intense band from 6.9 to 7.8 eV assigned to (1)pipi* (3(1)A(1) + 2(1)B(2)).

Negative ion formation in potassium–nitromethane collisions

Ion-pair formation in gaseous nitromethane (CH(3)NO(2)) induced by electron transfer has been studied by investigating the products of collisions between fast potassium atoms and nitromethane molecules using a crossed molecular-beam technique. The negative ions formed in such collisions were analysed using time-of-flight mass spectroscopy. The six most dominant product anions are NO(2)(-), O(-), CH(3)NO(2)(-), OH(-), CH(2)NO(2)(-) and CNO(-). By using nitromethane-d(3) (CD(3)NO(2)), we found that previous mass 17 amu assignment to O(-) delayed fragment, is in the present experiment may be unambiguously assigned to OH(-). The formation of CH(2)NO(2)(-) may be explained in terms of dissociative electron attachment to highly vibrationally excited molecules.

Electron transfer-induced fragmentation of thymine and uracil in atom-molecule collisions

Ion-pair formation has been studied in hyperthermal (30-100 eV) neutral potassium collisions with gas phase thymine (C(5)H(6)N(2)O(2)) and uracil (C(4)H(4)N(2)O(2)). Negative ions formed by electron transfer from the alkali atom to the target molecule were analysed by time-of-flight (TOF) mass spectrometry. The most abundant product anions are assigned to CNO(-) and (U-H)(-)/(T-H)(-) and the associated electron transfer mechanisms are discussed. Special emphasis is given to the enhancement of ring breaking pathways in the present experiments, notably CNO(-) formation, compared with free electron attachment measurements.

Electron attachment and electron ionization of acetic acid clusters embedded in helium nanodroplets

The effect of incident electrons on acetic acid clusters is explored for the first time. The acetic acid clusters are formed inside liquid helium nanodroplets and both cationic and anionic products ejected into the gas phase are detected by mass spectrometry. The cation chemistry (induced by electron ionization at 100 eV) is dominated by production of protonated acetic acid (Ac) clusters, Ac(n)H(+), although some fragmentation is also observed. In the case of anion production (at 2.8 eV electron energy) there is a clear distinction between the monomer and the clusters. For the monomer the dominant product is the dehydrogenated species, [Ac-H](-), whereas for the clusters both the parent anion, Ac(n)(-), and the dehydrogenated species, [Ac(n)-H](-), have similar abundances. A particularly intriguing contrast between the monomer and cluster anions is that helium atoms are seen attached to the latter whereas no evidence of helium atom attachment is found for the monomer. This surprising observation is attributed to the formation of acyclic (head-to-tail) acetic acid clusters in helium nanodroplets, which have more favourable electronic properties for binding helium atoms. The acyclic clusters represent a local minimum on the potential energy surface and in the case of the dimer this is distinct from the cyclic isomer (the global minimum) identified in gas phase experiments.

Valence shell electronic spectroscopy of isoprene studied by theoretical calculations and by electron scattering, photoelectron, and absolute photoabsorption measurements

The first ab initio calculations (vertical energies and oscillator strengths) are reported for the neutral electronic transitions of isoprene (2-methyl-1,3-butadiene), CH(2)CHC(CH(3))CH(2). The VUV photoabsorption spectroscopy of the molecule is presented in the energy range 4.6 to 10.8 eV (270-125 nm) with the highest resolution yet reported above 6.05 eV, revealing new spectral features. Valence and Rydberg transitions have been assigned in accordance with the theoretical results and the associated vibronic series have been analysed. The absolute photoabsorption cross sections at energies below 6.89 eV have been used to calculate the photolysis lifetime of isoprene in the upper stratosphere (20-50 km). Electron energy loss spectroscopy (EELS) measurements have enabled further photoabsorption cross sections to be derived in the range 9-28 eV. The first ab initio calculations have been carried out to determine excitation energies to the lowest energy ionic states of isoprene. The calculations are compared with the He(i) photoelectron spectrum (8 to 17 eV) and new vibrational structure is observed in the first photoelectron band.

Electron transfer processes in potassium collisions with 5-fluorouracil and 5-chlorouracil

Electron transfer to uracil (U), 5-chlorouracil (5-ClU) and 5-fluorouracil (5-FU) yielding anion formation has been investigated in 30-100 eV potassium-molecule collisions. The rich fragmentation patterns of all three molecules suggest that electron transfer in collisions with electronegative neutrals may cause efficient damage to RNA. The main ring fragment anion in all the mass spectra was NCO(-) while the production of X(-) (X = F, Cl) was a strong decomposition of the halouracil temporary negative ions. Cl(-) was the most intense fragment anion in the 5-chlorouracil measurements, whereas NCO(-) production dominated in the U and 5-FU data. Arguments based on energetics and vibrational dynamics have been proposed to explain these differences. Electronic coupling between dipole- and valence-bound states may play a particularly important role in the fragmentation pathways of the 5-ClU parent anion. The stabilizing influence of the potassium cation following electron transfer (ionic scattering) on the observed fragmentation patterns is discussed, notably in the context of comparisons with free electron attachment processes.

Electronic state spectroscopy of methyl formate probed by high resolution VUV photoabsorption, He(i) photoelectron spectroscopy and ab initio calculations.

The first ab initio calculations of the vertical excitation energies and oscillator strengths are presented for the neutral electronic transitions of methyl formate, C(2)H(4)O(2). The highest resolution VUV photoabsorption spectrum of the molecule yet reported is presented over the wavelength range 115 to 310 nm (10.8 to 4.0 eV) revealing several new spectral features. Valence and Rydberg transitions and their associated vibronic series, observed in the photoabsorption spectrum, have been assigned in accordance with new theoretical results. The calculations have been carried out to determine the excitation energies of the lowest energy ionic states of methyl formate and are compared with a newly recorded He(i) photoelectron spectrum (10.4 to 17.0 eV). New vibrational structure is observed in the first photoelectron band. The photoabsorption cross-sections have been used to calculate the photolysis lifetime of methyl formate in the upper stratosphere (20-50 km).

Synthesis, Cytotoxic Activity on Leukemia Cell Lines and Quantitative Structure-Activity Relationships (QSAR) Studies of Morita-Baylis-Hillman Adducts

BACKGROUND The Morita-Baylis-Hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential and promising biological profiles. The Morita-Baylis-Hillman adducts (MBHA) are a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs, e.g. as anti-Leishmania chagasi and Leishmania amazonensis, anti- Trypanosoma cruzi, anti-Plasmodium falciparum and Plasmodium berghei, lethal against Biomphalaria glabrata, antibacterial, antifungal, herbicide and others. METHODS The goal of this work is to describe the primary cytotoxic activities against strains of human leukemia HL-60 cell line for thirty-four Morita-Baylis- Hillman adducts (MBHA), followed by a Quantitative Structure-Activity Relationships study (QSAR). RESULTS The conventional or microwave-assisted syntheses of MBHA, derived from substituted aromatics or Isatin, were performed in good to excellent yields (70-100%) in short reaction times, using protocols recently developed by us. Isatin derivatives, MBHA 31 and 32, were the most active in this congener series of compounds, with IC50 values of 10.8 μM and 7.8 μM, respectively. The primary cytotoxic activities against chronic leukemia cells (K562) were also evaluated to these two most active compounds (MBHA 31 and 32), presenting IC50 values of 53 μM and 43 μM respectively. QSAR study was performed considering 3D, 2D and constitutional molecular descriptors. These were selected from Ordered Predictor Selection algorithm and submitted to Partial Least Squares Modeling. CONCLUSION We present an interesting investigation about cytotoxic activities on human leukemia cell line (HL-60) for 34 synthetic MBHA. In a good way we discovered that the most cytotoxic compounds (31-32, 10.8 μM and 7.8 μM respectively) were also prepared quantitatively (100% yields) in a short reaction time using microwave irradiation. We demonstrate that 31 and 32 induced apoptosis and not necrosis in HL-60 cells, observed by externalization of PS and increase Anexin-V positive cells. Quantitative Structure-Activity Relationships considering 3D, 2D and constitutional descriptors provided a robust and predictive PLS model, in accordance with SAR observations.

Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives

In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 2–7. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8a–c and aminoguanidine hydrochloride accessed by microwave irradiation. The aminoguanidine 5, 6 and 7 were prepared by reduction of guanylhydrazone 2–4 with sodium cyanoborohydride (94% yield of 5, and 100% yield of 6 and 7). The aromatic ketones 8a–c were prepared from the Barbier reaction followed by the Prins cyclization reaction (two steps, 63%–65% and 95%–98%). Cytotoxicity studies have demonstrated the effects of compounds 2–7 in various cancer and normal cell lines. That way, we showed that these compounds decreased cell viabilities in a micromolar range, and from all the compounds tested we can state that, at least, compound 3 can be considered a promising molecule for target-directed drug design.

Demethylation enhancement of 3-methyl-uracil and 1-methyl-thymine in atom-molecule collisions

We report the formation of demethylation in 3-methyl-uracil (3meU) and 1-methyl-thymine (1meT), i.e. (3meU-CH3)− and (1meT-CH3)−, through potassium-molecule collisions at different potassium kinetic energies. Study of the threshold of formation of this fragment can provide a value of threshold energy that can be compared with DEA studies.