Effectiveness of Green Cupric Oxide Nanoparticles for Walnut Storage Pest Management.

Walnut yield and quality are often affected by beetle infestations, particularly those caused by Carpophilus truncatus (Murray) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae). Beetle damage exposes walnuts to microbial food spoilers such as Fusarium species. Insecticides currently used for beetle control are environmentally unfriendly. This work explored a green synthesis approach for copper oxide nanoparticles (CuO-NPs) in a basic medium at 30°C by hydrolates, aqueous extracts obtained from Lippia integrifolia and Pimpinella anisum, denoted as CuO-I and CuO-A, respectively. Characterization through XRD, FT-IR, Raman, UV-visible absorbance, and AFM techniques indicated that CuO-A and CuO-I have a size ranging from 2-10 nm in height. The antifungal assay showed that both have a similar efficacy (MID = 320 µg), 3-fold stronger than CuO- NPs obtained in absence of hydrolates (denoted CuO-W) (MID = 960 µg), with the broadest inhibitory halos (ID = 126-128 mm) observed for CuO-A. Insecticidal activity of CuO-NPs showed a concentration-dependent behavior, with CuO-I showing an effect comparable to that of diatomaceous earth. SEM images confirmed the adhesion of nanoparticles to insect surfaces, which could induce oxygen deprivation and disruption of metabolic processes. Both CuO-A and CuO-I are promising for their use in integrated pest control in walnut storage.

Excito-repellent and Pesticide-Likeness Properties of Essential Oils on Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae).

Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae) are insect pests that cause severe damage in important walnut growing regions in the northwest of Argentina. The current management approaches for these pests involve the use of unsafe phosphorus pesticides whose overuse have led to farmworker poisoning, pest resistance issues, and environmental contamination. Plant extracts, particularly essential oils, are an alternative source of insect control agents. Excito-repellent essential oils can be used to develop ecofriendly tools for managing the pest population without affecting quality and visual appearance of the stored walnuts. Laboratory studies were conducted to assess the excito-repellent effects of C. dimidiatus and O. mercator of 12 essential oils derived from aromatic plants used as food additives and traditional medicine in Argentina: Aloysia citrodora (AC), Aloysia gratissima (AG), Aloysia gratissima var. Gratissima (AGG), Blepharocalyx salicipholius (BS), Hyptis mutabilis (HM), Lippia junelliana (LJ), Lippia turbinata (LT), Mentha x piperita (MP), Minthostachys mollis (MM), Minthostachys verticillata (MV), Origanum vulgare(OV), and Rosmarinus officinalis (RO). The most bioactive EOs (ERijk ≥ 70%) were Aloysia gratissima var. Gratissima (AGG), Minthostachys verticillata, and Lippia junelliana. Their bioactivity profile and chemical space, characterized from GC-MS measures, Generalized Estimating Equations, and Hierarchical Cluster Analysis, revealed that they are mixtures of very functionalized molecules with physicochemical properties similar to those of insecticides with low residual property that enter the insect body through the respiratory system by inhalation. The AGG, MV, and LJ oils are promising as protective agents of walnut products. In our laboratory, studies of their formulations for use in integrated pest management programs are still ongoing.

Chemical composition and insecticidal activity of essential oils from cultivated and native aromatic plants of Argentina against Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae).

Essential oils from aerial parts of six aromatic plants were analysed by GC-MS. The major compounds identified were γ-terpinene (11.5%), cuminaldehyde (26.6%) and γ-terpinen-7-al (40.6%) in Cuminum cyminum, trans-anethol (95.2%) in Pimpinella anisum, α-pinene (11.6%), limonene (21.0%), ß-caryophyllene (22.3%) and α-humulene (16.7%) in Lippia integrifolia, limonene (40.8%) and artemisia ketone (19.3%) in Lippia junelliana, trans-ß-ocimene (15.6%), 4-ethyl-4-methyl-1-hexene (24.5%), trans-tagetone (20.5%) and verbenone (27.2%) in Tagetes minuta, 1,8-cineole (17.9%),elixene (10.3%) and spathulenol (13.8%) in Aloysia gratissima. Oils with strong insecticidal activity on Carpophilus dimidiatus and Oryzaephilus mercator were from P. anisum (LC50 = 4 µl/L; LC100 = 10 µl/L) and T. minuta (LC50=10.19-12.57 µl/L; LC100=20 µl/L). Scents of C. cyminum and L. junelliana were strong insecticides on O. mercator (LC50=7.02-7.17 µl/L; LC100=10.00-20.00 µl/L). The insecticidal activity was associated to the whole content of C10 molecules and oxygenated constituents. The P. anisum oil is promising as protective agent of nut products.

QSAR models for the fumigant activity prediction of essential oils.

The Quantitative Structure-Activity Relationships (QSAR) theory, which allows predicting the insecticidal activity of chemical compounds through calculations from the molecular structure, is applied on 23 essential oils composed of 402 structurally diverse compounds at different chemical compositions. A large number of 114,871 conformation-independent molecular descriptors are computed through different types of freely available open-source programs. Mixture descriptors are calculated based on molecular descriptors of the essential oil components and their composition. The best resulting three-descriptor linear regression models are established through the Replacement Method variable subset selection approach. The results obtained in the present work are interesting for predicting the fumigant activity of these essential oil complex mixtures, by means of simple non-conformational QSAR models.

QSAR Study of Biologically Active Essential Oils against Beetles Infesting the Walnut in Catamarca, Argentina.

Essential oils from six species of aromatic plants collected in the Catamarca Province of Argentina were evaluated for their chemical composition and repellent and insecticidal activities against beetles of the genus Carpophilus (Coleoptera: Nitidulidae) and Oryzaephilus (Coleoptera: Silvanidae) that infest the local walnut production. Experimental data were analyzed using generalized estimating equations, with normal distribution and the identity link function. From the spectral information from the tested essential oils, we worked their molecular modeling as mixtures by developing mixture descriptors ( Dmix) that combined the molecular descriptor of each component in the mixture ( d i) and its relative concentration ( x i), i.e., Dmix = f( d i, x i). The application of chemoinformatic approaches determined that a combination of mixture descriptors related to molecular size, branchedness, charge distribution, and electronegativity were useful to explain the bioactivity profile against Carpophilus spp. and Oryzaephilus spp. The reported models were rigorously validated using stringent statistical parameters and essential oils reported with repellent activity against other beetle species from the Nitidulidae and Silvanidae families. This model confirmed each essential oil as a repellent with a comparable performance to the experimental reports.

QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo-Like Kinase 1.

The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (-logIC50) was predicted by QSAR modeling. Multivariate linear regression (MLR) was employed to model the relationship between 0D and 3D molecular descriptors and biological activities of molecules using the replacement method (MR) as variable selection tool. The 136 compounds were separated into several training and test sets. Two splitting approaches, distribution of biological data and structural diversity, and the statistical experimental design procedure D-optimal distance were applied to the dataset. The significance of the training set models was confirmed by statistically higher values of the internal leave one out cross-validated coefficient of determination (Q2) and external predictive coefficient of determination for the test set (Rtest2). The model developed from a training set, obtained with the D-optimal distance protocol and using 3D descriptor space along with activity values, separated chemical features that allowed to distinguish high and low pIC50 values reasonably well. Then, we verified that such model was sufficient to reliably and accurately predict the activity of external diverse structures. The model robustness was properly characterized by means of standard procedures and their applicability domain (AD) was analyzed by leverage method.

QSAR study for carcinogenicity in a large set of organic compounds.

In our continuing efforts to find out acceptable Absorption, Distribution, Metabolization, Elimination and Toxicity (ADMET) properties of organic compounds, we establish linear QSAR models for the carcinogenic potential prediction of 1464 compounds taken from the "Galvez data set", that include many marketed drugs. More than a thousand of geometry-independent molecular descriptors are simultaneously analyzed, obtained with the softwares E-Dragon and Recon. The variable subset selection method employed is the Replacement Method, and also the improved version Enhanced Replacement Method. The established models are properly validated through an external test set of compounds, and by means of the Leave-Group-Out Cross Validation method. In addition, we apply the Y-Randomization strategy and analyze the Applicability Domain of the developed model. Finally, we compare the results obtained in present study with the previous ones from the literature. The novelty of present work relies on the development of an alternative predictive structure-carcinogenicity relationship in a large heterogeneous set of organic compounds, by only using a reduced number of geometry independent molecular descriptors.

QSPR Study of Valproic Acid and Its Functionalized Derivatives.

This work establishes a Quantitative Structure-Property Relationships (QSPR) based analysis with the aim of interpreting both the structural and electronic properties of the polar region of valproic acid and its derivatives, in terms of stabilizing intramolecular interactions related to the involved substituents. We consider ten different calculated properties as dependent variables for the QSPR models: the bond lengths C8 O9 , C8 X10 , and the percentage of s-character of the natural hybrids forming the bonding σ orbitals of the O9 C8 X10 region. The representative descriptors are the charges transferred during donor/acceptor interactions around this function calculated at the B3LYP/6-311++G**(6d,10f) level of theory, and/or hybrid descriptors derived therefrom. The models so established result simple, predictive, and have a quite direct physical meaning.

Study of the structural and electronic properties of valproic acid and new derivatives used as anticonvulsant agents.

The conformational and electronic characteristics of the polar O(9)═C(8)-X(10) moiety in the anticonvulsant valproic acid (Vpa) drug and some of their amides and ester derivatives are analyzed at the B3LYP level using the 6-31+G(d,p) and 6-311++G(d,p) 6d,10f basis sets. Exploring the delocalization of the electron density of the O(9)═C(8)-X(10) moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O(9)═C(8)-X(10) is accompanied by a three-dimensional arrangement of donor and acceptor proton units closing nearly planar pseudorings of four, five, and six members arising from stabilizing interactions around the O(9)═C(8)-X(10) backbone. From the structure-property relationship analysis, we explain the origin of the change in the structural parameters and atomic charges in the polar moiety.

Theoretical characterization of SOME amides and esters DERIVATIVES of valproic acid.

The equilibrium structures, the planarity of the C(=O)X linkage and the nature of the chemical bond in the Y-C(=O)-XR(1)R(2) [where: Y= -CH-(CH(2)-CH(2)-CH(3))(2), X=N,O and R(1), R(2)= H; alkyl and aryl groups and lone pair electrons (lp)] molecular fragment of derivates of Valproic acid (Vpa) with antiepileptic activity were studied systematically by means of B3LYP calculations and topological analysis of the electron localization function (ELF). The covariance parameter cov[Omega(i), Omega(j)] reveals a dominating delocalization effect between the lone pair V(O(1)), V(X) and the electron density of the H-C and H-X(1) bonds resulting from the existence of not only non-conventional intramolecular hydrogen bonding patterns as C-H...O/N but also a weak closed-shell stabilizing interaction type arising from a dihydrogen bonding as C-H...H-N, where H...H contacts at a significantly shorter distance than twice the hydrogen atom van der Waals radius. The analyzed data derived from ELF domains were found to be in agreement with the known features and properties of the hydrogen bonding interactions discussed in this work.