Nanoencapsulation of extracts and isolated compounds of plant origin and their cytotoxic effects on breast and cervical cancer treatments: Advantages and new challenges.

This review analyzes the current progress in loaded nanoparticles (NPs) of plant extracts or isolated antineoplastic compounds used in breast and cervical cancer treatments. Also, it provides a comprehensive overview of the contributions made by traditional medicine and nanomedicine to the research of two of the most prevalent types of cancer in women worldwide: breast and cervical cancer. Searches were conducted in electronic databases to gather relevant information related to the biological activity of the NPs, which were meticulously reviewed. Nanomedicine has advanced to incorporate plant compounds including their crude extracts, in the preparation of NPs. The most used method is green synthesis, whose most outstanding advantages, is the reduced preparation time, and the variety of results that can be obtained depending on the reaction times, pH, temperature, and concentration of both the bio-reducing agent and the compound or plant extract. Most of the studies focus on evaluating crude extracts with high polarity, such as aqueous, alcoholic, and hydroalcoholic extracts. In conclusion, exploring the use of organic compounds is considered an area of opportunity for further research and future perspectives. Most of the analyzed studies were conducted using in vitro assays, highlighting the relatively recent nature of this field. It is expected that future research will involve more in vivo assays, particularly focusing on isolated cell lines representing the most difficult-to-treat types of cancer, such as triple-negative breast cancer like MDA-MB-231. Notably the MCF-7 cell line is one of the most used, while limited studies were found concerning cervical cancer.

Characterization of Silver Nanoparticle Systems from Microalgae Acclimated to Different CO2 Atmospheres.

Green synthesis of metallic nanoparticles using microalgae exposed to high CO2 atmospheres has not been studied in detail; this is of relevance in biological CO2 mitigation systems where considerable biomass is produced. In this study, we further characterized the potential of an environmental isolate Desmodesmus abundans acclimated to low and high CO2 atmospheres [low carbon acclimation (LCA) and high carbon acclimation (HCA) strains, respectively] as a platform for silver nanoparticle (AgNP) synthesis. As previously characterized, cell pellets at pH 11 were selected from the biological components tested of the different microalgae, which included the culture collection strain Spirulina platensis. AgNP characterization showed superior performance of strain HCA components as preserving the supernatant resulted in synthesis in all pH conditions. Size distribution analysis evidenced strain HCA cell pellet platform (pH 11) as the most homogeneous AgNP population (14.9 ± 6.4 nm diameter, -32.7 ± 5.3 mV) followed by S. platensis (18.3 ± 7.5 nm, -33.9 ± 2.4 mV). In contrast, strain LCA presented a broader population where the size was above 100 nm (127.8 ± 14.8 nm, -26.7 ± 2.4 mV). Fourier-transform infrared and Raman spectroscopies showed that the reducing power of microalgae might be attributed to functional groups in the cell pellet from proteins, carbohydrates, and fatty acids and, in the supernatant, from amino acids, monosaccharides, disaccharides, and polysaccharides. Microalgae AgNPs exhibited similar antimicrobial properties in the agar diffusion test against Escherichia coli. However, they were not effective against Gram (+) Lactobacillus plantarum. It is suggested that a high CO2 atmosphere potentiates components in the D. abundans strain HCA for nanotechnology applications.

Synthesis and Characterization of Rutile TiO2 Nanoparticles for the Toxicological Effect on the H9c2 Cell Line from Rats.

The widespread use of titanium dioxide (TiO2) has raised concerns about potential health risks associated with its cytotoxicity in the cardiovascular system. To evaluate the cytotoxicity of TiO2 particles, the H9c2 rat cardiomyoblasts were used as a biological model, and their toxicological susceptibility to TiO2-anatase and TiO2-rutile particles was studied in vitro. The study examined dose and time exposure responses. The cell viability was evaluated based on metabolic inhibition and membrane integrity loss. The results revealed that both TiO2-anatase and TiO2-rutile particles induced similar levels of cytotoxicity at the inhibition concentrations IC25 (1.4-4.4 µg/cm2) and IC50 (7.2-9.3 µg/cm2). However, at more significant concentrations, TiO2-rutile appeared to be more cytotoxic than TiO2-anatase at 24 h. The study found that the TiO2 particles induced apoptosis events, but necrosis was not observed at any of the concentrations of particles used. The study considered the effects of microstructural properties, crystalline phase, and particle size in determining the capability of TiO2 particles to induce cytotoxicity in H9c2 cardiomyoblasts. The microstress in TiO2 particles was assessed using powder X-ray diffraction through Williamson-Hall and Warren-Averbach analysis. The analysis estimated the apparent crystallite domain and microstrain of TiO2-anatase to be 29 nm (ε = 1.03%) and TiO2-rutile to be 21 nm (ε = 0.53%), respectively. Raman spectroscopy, N2 adsorption isotherms, and dynamic light scattering were used to identify the presence of pure crystalline phases (>99.9%), comparative surface areas (10 m2/g), and ζ-potential values (-24 mV). The difference in the properties of TiO2 particles made it difficult to attribute the cytotoxicity solely to one variable.

Scanning Tunneling Microscopy of Biological Structures: An Elusive Goal for Many Years.

Scanning tunneling microscopy (STM) is a technique that can be used to directly observe individual biomolecules at near-molecular scale. Within this framework, STM is of crucial significance because of its role in the structural analysis, the understanding the imaging formation, and the development of relative techniques. Four decades after its invention, it is pertinent to ask how much of the early dream has come true. In this study, we aim to overview different analyses for DNA, lipids, proteins, and carbohydrates. The relevance of STM imaging is exhibited as an opportunity to assist measurements and biomolecular identification in nanobiotechnology, nanomedicine, biosensing, and other cutting-edge applications. We believe STM research is still an entire science research ecosystem for joining several areas of expertise towards a goal settlement that has been elusive for many years.

Advances in the Structural Strategies of the Self-Assembly of Photoresponsive Supramolecular Systems.

Photosensitive supramolecular systems have garnered attention due to their potential to catalyze highly specific tasks through structural changes triggered by a light stimulus. The tunability of their chemical structure and charge transfer properties provides opportunities for designing and developing smart materials for multidisciplinary applications. This review focuses on the approaches reported in the literature for tailoring properties of the photosensitive supramolecular systems, including MOFs, MOPs, and HOFs. We discuss relevant aspects regarding their chemical structure, action mechanisms, design principles, applications, and future perspectives.

Amorphous SiO2 nanoparticles promote cardiac dysfunction via the opening of the mitochondrial permeability transition pore in rat heart and human cardiomyocytes.

BACKGROUND: Silica nanoparticles (nanoSiO2) are promising systems that can deliver biologically active compounds to tissues such as the heart in a controllable manner. However, cardiac toxicity induced by nanoSiO2 has been recently related to abnormal calcium handling and energetic failure in cardiomyocytes. Moreover, the precise mechanisms underlying this energetic debacle remain unclear. In order to elucidate these mechanisms, this article explores the ex vivo heart function and mitochondria after exposure to nanoSiO2. RESULTS: The cumulative administration of nanoSiO2 reduced the mechanical performance index of the rat heart with a half-maximal inhibitory concentration (IC50) of 93 µg/mL, affecting the relaxation rate. In isolated mitochondria nanoSiO2 was found to be internalized, inhibiting oxidative phosphorylation and significantly reducing the mitochondrial membrane potential (ΔΨm). The mitochondrial permeability transition pore (mPTP) was also induced with an increasing dose of nanoSiO2 and partially recovered with, a potent blocker of the mPTP, Cyclosporine A (CsA). The activity of aconitase and thiol oxidation, in the adenine nucleotide translocase, were found to be reduced due to nanoSiO2 exposure, suggesting that nanoSiO2 induces the mPTP via thiol modification and ROS generation. In cardiac cells exposed to nanoSiO2, enhanced viability and reduction of H2O2 were observed after application of a specific mitochondrial antioxidant, MitoTEMPO. Concomitantly, CsA treatment in adult rat cardiac cells reduced the nanoSiO2-triggered cell death and recovered ATP production (from 32.4 to 65.4%). Additionally, we performed evaluation of the mitochondrial effect of nanoSiO2 in human cardiomyocytes. We observed a 40% inhibition of maximal oxygen consumption rate in mitochondria at 500 µg/mL. Under this condition we identified a remarkable diminution in the spare respiratory capacity. This data indicates that a reduction in the amount of extra ATP that can be produced by mitochondria during a sudden increase in energy demand. In human cardiomyocytes, increased LDH release and necrosis were found at increased doses of nanoSiO2, reaching 85 and 48%, respectively. Such deleterious effects were partially prevented by the application of CsA. Therefore, exposure to nanoSiO2 affects cardiac function via mitochondrial dysfunction through the opening of the mPTP. CONCLUSION: The aforementioned effects can be partially avoided reducing ROS or retarding the opening of the mPTP. These novel strategies which resulted in cardioprotection could be considered as potential therapies to decrease the side effects of nanoSiO2 exposure.

Technetium-Radiolabeled Mannose-Functionalized Gold Nanoparticles as Nanoprobes for Sentinel Lymph Node Detection.

Gold nanoparticles (AuNPs) are considered valuable nanomaterials for the design of radiolabeled nanoprobes for single-photon emission computed tomography (SPECT) imaging. Radiolabeled and functionalized AuNPs could improve lymphatic mapping by enhancing the radioactive signaling of individual particles in the sentinel node. In this study, an alternative method for functionalizing commercial AuNps with mannose is described. The chemical derivatization and biofunctionalization of AuNPs were performed with lipoic acid and mannose, respectively. Several levels of mannose were tested; the thiolate hydrazinonicotinamide-glycine-glycine-cysteine (HYNIC) molecule was also used for 99mTc radiolabeling. Physicochemical characterization of this system includes U-V spectroscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and transmission electron microscopy. The most stable nanoprobe, in terms of the aggregation, radiolabeling efficiency, and purity, was tested in a sentinel lymph node model in a rat by microSPECT/computed tomography (CT) imaging. The SPECT images revealed that 99mTc-radiolabeled AuNPs functionalized with mannose can track and accumulate in lymph nodes in a similar way to the commercial 99mTc-Sulfur colloid, commonly used in clinical practice for sentinel lymph node detection. These promising results support the idea that 99mTc-AuNPs-mannose could be used as a SPECT contrast agent for lymphatic mapping.

Dispersion-Corrected Density Functional Theory Study of the Noncovalent Complexes Formed with Imidazo[1,2-a]pyrazines Adsorbed onto Silver Clusters.

Imidazo[1,2-a]pyrazines are cyclic amidine-type compounds composed of α-amino acid residues. A full structural identification of these molecules constitutes an analytical challenge, especially when imidazo[1,2-a]pyrazines are obtained from physical processes (e.g., sublimation and pyrolysis of amino acids). A valuable source of molecular information can be obtained from absorption spectroscopies and related techniques encompassing the use of metallic substrates. The aim of this study is to provide new knowledge and insights into the noncovalent intermolecular interactions between imidazo[1,2-a]pyrazines and two Ag n (n = 4 and 20) clusters using density functional theory (DFT) methods. Semiempirical DFT dispersion (DFT-D) corrections were addressed using Grimme's dispersion (GD2) and Austin-Petersson-Frisch (APF) functionals in conjunction with the 6-31+G(d,p) + LANL2DZ mixed basis set. These DFT-D methods describe strong interactions; besides, in all cases, the APF dispersion (APF-D) energies of interaction appear to be consistently overestimated. In comparison with B3LYP calculations, the mean values for the difference in the energies of interaction calculated are 2.25 (GD2) and 6.24 (APF-D) kcal mol-1 for Ag4-molecules, and 2.30 (GD2) and 8.53 (APF-D) kcal mol-1 for Ag20-molecules. The effect of applying GD2 and APF-D corrections to the noncovalent complexes is nuanced in the intermolecular distances calculated, mainly in the Ag···N(amidine) bonding, which appears to play the most important role for the adsorptive process. Selective enhancement and considerable red shifts for Raman vibrations suggest strong interactions, whereas a charge redistribution involving the metallic substrate and the absorbate leads to a significant rearrangement of frontier molecular orbitals mainly in the Ag20-molecule complexes. Finally, time-dependent DFT calculations were carried out to access the orbital contributions to each of the transitions observed in the absorption spectrum. The corresponding UV-vis spectra involve transitions in the visible region at around 400 and 550 nm for the Ag4-molecule and the Ag20-molecule complexes, respectively.

A dispersion-corrected density functional theory study of the noncovalent interactions between nucleobases and carbon nanotube models containing stone-wales defects.

The noncovalent bonding between nucleobases (NBs) and Stone-Wales (SW) defect-containing closed-end single-walled carbon nanotubes (SWNTs) was theoretically studied in the framework of density function theory using a dispersion-corrected functional PBE-G06/DNP. The models employed in this study were armchair nanotube (ANT) (5,5) and zigzag nanotube (ZNT) (10,0), which incorporated SW defects in different orientations. In one of them, the (7,7) junction is tilted with respect to SWNT axis (ANT-t and ZNT-t), whereas in ANT-p and ZNT-p models the (7,7) junction is parallel and perpendicular to the axis, respectively. The binding energies for uracil, thymine, cytosine, 5-methylcytosine, adenine, and guanine interacting with the defect-containing nanotube models were compared to the values previously obtained with the same calculation technique for the case of defect-free SWNTs, both in the gas phase (vacuum) and in aqueous medium. For most models, the interaction strength tends to be higher for purine than for pyrimidine complexes, with a clear exception of the systems including ZNT-p, both in vacuum and in aqueous medium. As it could be expected, the binding strength in the latter case is lower as compared to that in vacuum, roughly by 2-4 kcal/mol, due to the implicit inclusion of a medium (i.e., water) via the conductor-like screening model model. The closest contacts between NBs and SWNT models, frontier orbital distribution, and highest-occupied molecular orbital-lowest-unoccupied molecular orbital gap energies are analyzed as well. © 2019 Wiley Periodicals, Inc.

Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells.

Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC-1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.

Enhancing internalization of silica particles in myocardial cells through surface modification.

Surface modification in nanostructured mesoporous silica particles (MSNs) can significantly increase the uptake in myocardial cells. Herein, MSNs particles were synthesized and chemically functionalized to further assess their biocompatibility in rat myocardial cell line H9c2. The surface modification resulted in particles with an enhanced cellular internallization (3-fold increase) with respect to pristine particles. Apoptosis events were not evident at all, while necrosis incidence was significant only at a higher doses (>500µg/mL). In particular, the percentage of necrotic cells decrease in a statistically significant manner for the functionalized particles at lower doses than 100µg/mL. This study concludes that the proposed surface functionalization of MSNs particles does not compromise their viability on H9c2 cells, and therefore they could potentially be used for biomedical purposes. Fourier-transform infrared, Raman, TGA/DSC, N2 adsorption-desorption, and TEM techniques were used to characterize the as-prepared materials. Confocal microscopy and flow cytometry analyses were carried out to measure the histograms of cell complexity and the half maximal inhibitory concentration, respectively. Reactive oxygen species generation was accessed using assays with MitoSOX and Amplex Red fluoroprobes.

Differential cytotoxicity and internalization of graphene family nanomaterials in myocardial cells.

Given the well-known physical properties of graphene oxide (GO), numerous applications for this novel nanomaterial have been recently envisioned to improve the performance of biomedical devices. However, the toxicological assessment of GO, which strongly depends on the used material and the studied cell line, is a fundamental task that needs to be performed prior to its use in biomedical applications. Therefore, the toxicological characterization of GO is still ongoing. This study contributes to this, aiming to synthesize and characterize GO particles and thus investigate their toxic effects in myocardial cells. Herein, GO particles were produced from graphite using the Tour method and subsequent mild reduction was carried out to obtain low-reduced GO (LRGO) particles. A qualitative analysis of the viability, cellular uptake, and internalization of particles was carried out using GO (~54% content of oxygen) and LRGO (~37% content of oxygen) and graphite. GO and LRGO reduce the viability of cardiac cells at IC50 of 652.1±1.2 and 129.4±1.2µg/mL, respectively. This shows that LRGO particles produce a five-fold increase in cytotoxicity when compared to GO. The cell uptake pattern of GO and LRGO particles demonstrated that cardiac cells retain a similar complexity to control cells. Morphological alterations examined with electron microscopy showed that internalization by GO and LRGO-treated cells (100µg/mL) occurred affecting the cell structure. These results suggest that the viability of H9c2 cells can be associated with the surface chemistry of GO and LRGO, as defined by the amount of oxygen functionalities, the number of graphitic domains, and the size of particles. High angle annular dark-field scanning transmission electron microscopy, dynamic light-scattering, Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopies were used to characterize the as-prepared materials.

Enhanced Enzymatic Activity of Laccase (from Pycnoporus sanguineus CS43) Immobilized on Sputtered Nanostructured Gold Thin Films.

Functionalization of thin films with organic ligands has been the subject of intense research due to their potential application as heterogeneous molecular nanosystems. In this work, self-assembled monolayers of thiols (16-mercaptohexadecanoic acid and 11-mercaptoundecanol) were used to bind laccase (from Pycnoporus sanguineus CS43) to nanostructured gold thin films obtained by DC sputtering. Sputtering power, sputtering pressure and substrate temperature were optimized to enhance the activity of the immobilized biomolecules. Scanning electron microscopy, confocal microscopy, X-ray diffraction and UV-vis spectroscopy were used to characterize the SAM-functionalized gold substrates. Our results demonstrate that the highest immobilized enzyme activity values can be achieved on substrates of surface roughness ˜200 nm and Au particle size of about 14 nm. The outstanding quality of the as-prepared substrates makes them particularly attractive as bionanosensors.

Nanostructured diamine-fullerene derivatives: computational density functional theory study and experimental evidence for their formation via gas-phase functionalization.

Nanostructure derivatives of fullerene C(60) are used in emerging applications of composite matrices, including protective and decorative coating, superadsorbent material, thin films, and lightweight high-strength fiber-reinforced materials, etc. In this study, quantum chemical calculations and experimental studies were performed to analyze the derivatives of diamine-fullerene prepared by the gas-phase solvent-free functionalization technique. In particular, the aliphatic 1,8-diamino-octane and the aromatic 1,5-diaminonaphthalene, which are diamines volatile in vacuum, were studied. We addressed two alternative mechanisms of the amination reaction via polyaddition and cross-linking of C(60) with diamines, using the pure GGA BLYP, PW91, and PBE functionals; further validation calculations were performed using the semiempirical dispersion GGA B97-D functional which contains parameters that have been specially adjusted by a more realistic view on dispersion contributions. In addition, we looked for experimental evidence for the covalent functionalization by using laser desorption/ionization time-of-flight mass spectrometry, thermogravimetric analysis, and atomic force microscopy.

Aggregation of human serum albumin on graphite and single-walled carbon nanotubes as studied by scanning probe microscopies.

Human serum albumin (HSA) is the most abundant protein in blood plasma showing a remarkable ability to bind a broad range of hydrophobic substrates. We employed scanning tunneling microscopy and atomic force microscopy to characterize the morphology of HSA aggregates on highly-ordered pyrolytic graphite (HOPG) and single-walled carbon nanotubes (SWNTs). The morphologies found for albumin aggregates on HOPG are quite different from the ones observed on SWNTs. On HOPG, HSA forms aggregates of roughly 10-20 molecules; single protein molecules were observed as well. In the case of SWNTs, nanotubes were partially or totally covered with HSA, exhibiting four general types of aggregation: (i) SWNT sidewalls contain single molecules of albumin which are away from each other at distances longer than the HSA molecular size; (ii) SWNTs are completely covered with HSA, which forms a thin and relatively homogeneous layer; (iii) SWNTs have a complete layer of HSA with additional accumulation of protein at separate sites; and (iv) several SWNTs totally covered with albumin assemble into a bundle-like structure common for bare nanotubes. These observations are interpreted in terms of stronger interactions of HSA with nanotube sidewalls than with flat graphite surface.

"Green" functionalization of pristine multi-walled carbon nanotubes with long-chain aliphatic amines.

Short pristine multi-walled carbon nanotubes (MWNTs) were functionalized with a series of long-chain (including polymeric) aliphatic amines, namely octadecylamine (ODA), 1,8-diaminooctane (DO), polyethylene glycol diamine (PEGDA) and polyethylenimine (PEI), via two "green" approaches: (1) gas-phase functionalization (for volatile ODA and DO) and (2) direct heating in the melt (for polymeric PEGDA and PEI). Both of them consist in one-step reaction between MWNTs and amine without the use of organic solvents. The nanostructures obtained were characterized by using infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. It was observed that both solvent-free methods were efficient in the nanotube functionalization, and the nanostructures of variable solubility and morphology were obtained depending on the amines attached. ODA, PEGDA and PEI-functionalized MWNTs were found to be soluble in propanol, meanwhile the MWNTs-PEGDA and MWNTs-PEI were soluble in water as well. The attachment of 1,8-diaminooctane onto MWNTs resulted in cross-linked stable nanostructure.

Regioselectivity in azahydro[60]fullerene derivatives: application of general-purpose reactivity indicators.

To attempt theoretical predictions of the regioselectivity pattern in molecules with multiple reactive sites, the energies of formation of all possible isomers are usually considered. This means that the computing becomes highly demanding if high theoretical levels are used. The study objective was to predict the regioselectivity in the reaction of hydrogen addition onto azahydro[60]fullerene C 59H n+1 N ( n = 0-4) systems using a new reactivity indicator termed general-purpose reactivity indicator, Xi Delta N

Low-symmetry structures of Au32Z (Z = +1, 0, -1) clusters.

In this work, we have explored new stable structures of the Au32Z (Z = +1, 0, -1) clusters. Theoretical calculations using density functional theory within the generalized-gradient approximation were performed. Our results show that, in the anion state (Au32-), low-symmetry (disordered) structures are preferred over the caged fullerene-like isomer. In addition, the cationic cluster (Au32+) also exhibits a disordered low-symmetry structure as its lowest energy configuration, but it is much closer in energy to the fullerene-like isomer. These results, obtained at T = 0 K, indicate that disordered structures for the Au32- and Au32+ clusters may be detected not only at room temperature, as was experimentally verified for the Au32- one, but also at much lower temperatures.

Imidazo[1,2-a]pyrazine-3,6-diones derived from alpha-amino acids: a theoretical mechanistic study of their formation via pyrolysis and silica-catalyzed process.

Imidazo[1,2-a]pyrazine-3,6-diones are unusual compounds composed of three alpha-amino acid fragments. These bicyclic amidines (BCAs) form under high temperatures or with the use of strong dehydrating reagents. We gave insight into the mechanisms of BCA formation via gas-phase pyrolytic and silica-catalyzed reactions of glycine (Gly) and alpha-aminoisobutyric acid (AIB) with related diketopiperazines (DKPs), using quantum chemical calculations. The entire process requires four steps: (1) O-acylation of DKP with free or silica-bonded amino acid, (2) acyl transfer from the oxygen to the nitrogen atom, (3) intramolecular condensation of the N-acyl DKP into a cyclol, and (4) elimination of water. To study step (1) at silica surface (modeled by H7Si8O12-OH cluster), we employed two-level ONIOM calculations (AM1:UFF, B3LYP/3-21G:UFF and B3LYP/6-31G(d):UFF); all gas-phase reactions were studied at the AM1, B3LYP/3-21G and B3LYP/6-31G(d) levels. The catalytic effect of silica was observed for both Gly and AIB: the activation energy in the O-acylation at the surface was lower by more than 9 kcal mol(-1) as compared to the gas-phase process. Contrary to the exothermic O-acylation, the gas-phase transfer reaction (step 2) was exothermic in both cases, but more favorable for Gly. The cyclocondensation of N-acylated DKPs into BCAs (steps 3 and 4) is endothermic for Gly and exothermic for AIB.

Theoretical prediction of gas-phase infrared spectra of imidazo[1,2-a]pyrazinediones and imidazo[1,2-a]imidazo[1,2-d]pyrazinediones derived from glycine.

Imidazo[1,2-a]pyrazine-3,6-diones and imidazo[1,2-a]imidazo[1,2-d]pyrazine-3,8-diones can be produced by pyrolysis of simple amino acids. While such bicyclic and tricyclic amidines were detected and characterized by IR spectroscopy for some alpha-substituted amino acids, the parent systems composed of glycine fragments are unknown up to now. IR spectra for five amidines derived from glycine were calculated by using different semi-empirical (PM3, AM1, MNDO and MINDO/3), HF, and hybrid DFT (B3LYP, B3P86 and B3PW91) methods in conjunction with 6-31G(d) basis set (for HF and DFT). Vibration frequencies in the experimental IR spectra were predicted based upon the B3LYP data, by correcting the calculated wavenumbers by a scaling factor of 0.959. The behavior of most characteristic bands (nu(CX), nu(NH), etc.) and their shifts with respect to such bands in the spectra of alanine and alpha-aminoisobutyric acid derivatives studied before, are discussed. Performance of the semi-empirical methods was tested, bearing in mind possible future needs for IR spectra predictions for larger molecular systems of similar chemical nature; the use of MINDO/3 and MNDO is recommended. A basis set effect on the B3LYP fundamental vibration frequencies for hexahydroimidazo[1,2-a]pyrazine-3,6-dione was studied by varying Pople basis sets from minimal STO-3G to 6-311++G(d, p). No significant improvements were found beyond the 6-31G(d) basis set, which thus can be recommended to predict IR spectra for the amidines and similar molecules.