M. J. Sottomayor

Abstract Persistent pesticide transformation products (TPs) are increasingly being detected among different environmental compartments, including groundwater and surface water. However, there is no sufficient experimental data on their toxicological potential to assess the risk associated with TPs, even if their occurrence is known. In this study, the interaction of chlorophenoxy herbicides (MCPA, mecoprop, 2,4-D and dichlorprop) and their main transformation products with calf thymus DNA by UV-visible absorption spectroscopy has been assessed. Additionally, the toxicity of the chlorophenoxy herbicides and TPs was also assessed evaluating the inhibition of acetylcholinesterase activity. On the basis of the results found, it seems that AChE is not the main target of chlorophenoxy herbicides and their TPs. However, the results found showed that the transformation products displayed a higher inhibitory activity when compared with the parent herbicides. The results obtained in the DNA interaction studies showed, in general, a slight effect on the stability of the double helix. However, the data found for 4-chloro-2-methyl-6-nitrophenol suggest that this transformation product can interact with DNA through a noncovalent mode.

Abstract Herbicides are important for the control of weed growth but increasing use causes environmental problems and undesirable side effects in crops. Phenoxy acid herbicides with auxin-like activity have been used against grass and broad leaf weeds in many crops, such as rice, winter wheat and soybean. Carcinogenicity in humans and embryotoxicity in animals have been described as the main hazards of phenoxy acid herbicides. Thermal denaturation of double stranded DNA has been used as a measure of the effect of harmful chemical substances on the structure and stability of the DNA molecule. Hence, the interaction between several phenoxy acid herbicides (phenoxyacetic acid, 4- chlorophenoxyacetic acid, MCPA, mecoprop, 2,4-D and dichlorprop) and Calf thymus DNA was assessed by UV-Vis absorption spectroscopy. UV spectra and melting curves have been recorded for solutions at constant DNA concentration and using different concentrations of each of the herbicides under study. The transition temperature values and the thermodynamic parameters of DNA thermal denaturation have been determined. The studies performed so far help to understand herbicide-DNA interactions gathering suitable information for the (re)design of new molecules with lower potential risk to humans.

Abstract The energetic study of 4-nitro-2,1,3-benzothiadiazole has been developed using experimental techniques together with computational approaches. The standard (p degrees = 0.1 MPa) molar enthalpy of formation of crystalline 4-nitro-2,1,3-benzothiadiazole (181.9 +/- 2.3 kJ . mol(-1)) was determined from the experimental standard molar energy of combustion -(3574.3 +/- 1.3) kJ . mol(-1), in oxygen, measured by rotating-bomb combustion calorimetry at T = 298.15 K. The standard (p degrees = 0.1 MPa) molar enthalpy of sublimation, at T = 298.15 K, (101.8 +/- 4.3) kJ . mol(-1), was determined by a direct method, using the vacuum drop micro-calorimetric technique. From the latter value and from the enthalpy of formation of the solid, it was calculated the standard (p degrees = 0.1 MPa) enthalpy of formation of gaseous 4-nitro-2,1,3-benzothiadiazole as (283.7 +/- 4.9) kJ . mol(-1). Standard ab initio molecular orbital calculations were performed using the G3(MP2)//B3LYP composite procedure and several working reactions in order to derive the standard molar enthalpy of formation 4-nitro-2,1,3-benzothiadiazole. The ab initio results are in good agreement with the experimental data.

Abstract In recent years flavonoids have attracted a great interest as potential therapeutic drugs against a wide range of diseases. While the antioxidant activity of these natural polyphenolic compounds is well known, their binding to DNA characteristics is not fully understood despite the fact that many of them exert their biological effects by reversibly binding to nucleic acids. The present study aims to investigate the interaction of flavone and four hydroxyflavone isomers with double stranded DNA, occurring in bulk solution. A combination of micro-DSC and UV spectroscopy has been used to study the effect of these compounds and of their structure on the structure and stability of the DNA molecule. The characteristics of DNA thermal denaturation have been used as a measure of the effect of the compounds on the stability of the double helix. Micro-DSC has been used to determine the temperature dependence of the heat capacity of the process of thermal denaturation of DNA in solutions containing flavone and the following hydroxyflavones: 3-hydroxyflavone, 5-hydroxyflavone, 6-hydroxyflavone and 7-hydroxyflavone. The observed enthalpy of transition and the transition temperature of DNA thermal denaturation were determined for each compound. UV thermal denaturation curves were also recorded, under the same experimental conditions as the DSC measurements. The transition temperature values and the thermodynamic parameters of thermal denaturation were determined. Differential scanning calorimetry and ultraviolet spectroscopy measurements have evidenced an interaction between the studied flavones and DNA, showing a stabilization of DNA structure, due mainly to intercalation of the flavones. The results also show a noteworthy effect of the structure of the hydroxyflavone isomers on this stabilization.

Abstract The present work reports the values of the standard (p degrees = 0.1 MPa) molar energies of combustion for the liquid isomers methyl picolinate and methyl isonicotinate and for the crystalline isomer methyl nicotinate measured by static bomb calorimetry. The molar enthalpies of vaporization of the three isomers at T = 298.15 K as well as the molar enthalpies of sublimation of two of them (methyl picolinate and methyl nicotinate) were derived from vapor pressure measurements at different temperatures using a static method. The molar enthalpies of vaporization at T = 298.15 K of methyl picolinate and methyl isonicotinate were also measured using Calvet microcalorimetry. The thermal behavior of the compounds was studied by differential scanning calorimetry, and the temperatures and the molar enthalpies of fusion were determined using this technique. The experimental results were used to derive the gaseous standard molar enthalpies of formation, at 298.15 K, of the three pyridinecarboxylic acid methyl ester isomers and the triple points of the ortho and meta isomers.