Top Molecules Research Articles

Abstract 536: Novel identification of STAT1 as a crucial mediator of ETV6-NTRK3-induced tumorigenesis

Abstract Chromosomal rearrangements that facilitate tumor formation and progression through activation of oncogenic tyrosine kinase are frequently observed in cancer. The ETV6-NTRK3 (EN) fusion has been implicated in various cancers, including infantile fibrosarcoma, secretory breast carcinoma and acute myeloblastic leukemia, and has exhibited in vivo and in vitro transforming ability. In the present study, we analyzed transcriptome alterations using RNA-Seq in EN-transduced NIH3T3 fibroblasts to identify the mechanisms that are involved in EN-mediated tumorigenesis. Through functional profile assessment of EN-regulated transcriptome alterations, we found that EN up-regulated genes mainly associated with cell motion, membrane invagination, and cell proliferation, while down-regulated genes are involved in cell adhesion, which described the transforming potential and increased proliferation in EN-transduced cells. Notably, KEGG pathway analysis identified the JAK-STAT signaling pathway with the highest statistical significance. Moreover, Ingenuity Pathway Analysis and gene regulatory network analysis identified the Stat1 transcription factor and its target genes as top EN-regulated molecules. We further demonstrated that EN enhanced STAT1 phosphorylation but attenuated STAT1 acetylation, thereby inhibiting the interaction between NF-κB p65 and acetylated STAT1. Consequently, nuclear translocation of NF-κB p65 and subsequent anti-apoptotic NF-κB activity were increased by EN. Taken together, here we report, for the first time, STAT1 as a significantly EN-regulated transcription factor and a crucial mediator of EN-induced tumorigenesis. [This work was supported by a National Research Foundation grant of Korea (NRF-2014M3A9B5073918) funded by the Korea government.] Citation Format: Jinah Park, Junil Kim, Poul H. Sorensen, Seong-Jin Kim. Novel identification of STAT1 as a crucial mediator of ETV6-NTRK3-induced tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 536. doi:10.1158/1538-7445.AM2017-536

Rotovibrational states of the water molecule on the sun.

The infrared spectrum of water observed in sunspots is complex and dense, with bands separated by approximately 0.01cm-1. For top asymmetrical molecules, there is no theoretical approach that allows for the calculation of rotovibrational energy with such precision. Experimentally derived rotovibracional energy levels of water at high temperatures combined with variational calculations have been used for the band assignments. These energy levels are employed to refine the analysis of a small portion of the infrared absorption spectrum. Such procedure has allowed for the identification of additional 55 bands to the 70 already identified as rotovibrational transitions of the water molecule. Our new assignments, which include pure and cross transitions, offer additional evidence of the existence of water on the sun, but above all they illustrate the complexity of the solar spectrum that involves states with higher levels of rotational excitation. Given the conditions on the sun, more molecules of water would occur in excited electronic states, which include apolar and paramagnetic states, generating intense bands in the spectrum. Since there is an analytical solution for the rotovibrational transitions of linear molecules, we were able to identify 16 bands relative to the excited electronic states 1B2 and 3A1 in the sunspot spectrum. Density functional B3LYP/AUG-cc-pVTZ calculations of the electric and magnetic dipole are employed to discuss some consequences of the presence of excited states of water in the dynamics of sunspots and solar magnetic field.

Abstract 12334: A Flavor of Metabolic Disease in Pulmonary Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a severe occlusive vascular disease of the lungs. One of the primary origin of PAH is pulmonary endothelial dysfunction driving vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Interestingly, endothelial dysfunction is maintained in culture, out of fluid and hemodynamic stress, humoral/hormonal, and inflammatory environment. Hypothesis: This aberrant phenotype may be imprinted in pulmonary endothelial cells (PEC) DNA though a specific pattern of DNA methylations. Methods: Genomic DNA was extracted from cultured PEC (passage 3): idiopathic PAH (n=11), heritable PAH (BMPR2 mutation carriers, n=10), controls (n=18). DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium HumanMethylation450 Bead Chip. We normalized all arrays against each other using functional normalization. Differentially methylated sites were clustered with Cluster3.0 and heatmap were obtained with Treeview. Results: We discriminated controls vs PAH into 2 clusters of hypermethylated loci (119 probes= 31 promoters) and hypomethylated loci (331 probes= 116 promoters). Interestingly, 46 promoters/147 (clusters 1+2) (31%) were related to metabolic diseases (Ingenuity pathway analysis), and top molecules (fold changes up- and down regulated) includes molecules highly involved in cellular lipid metabolic process (ABCA1, Q=0.002 and ABCB4, Q=0.003), regulation of glucogenesis (ACN9, Q=2.78.10-5), lipid and glucose metabolism (ADIPOQ, Q=10-4), and insulin sensitivity and metabolism of glucose and lipids (miR-26a, Q=0.005), among others. Conclusions: the methylation fingerprint of PAH highlighted a set of molecules involved in metabolic disease and metabolism regulation. This may have fundamental and clinical implications in PAH.

Biosimilar medicines: creating sustainable competition in an era of a new patent cliff in biological medicines

For many years European governments have sought to ensure a high degree of competition in off-patent pharmaceutical markets in order to generate price competition - and consequently benefits such as improved patient access or savings for payers after patent expiry. The pharmaceutical industry believes that access to valuable new treatments and post-exclusivity competition are essential for the sustainability of healthcare systems. Biological medicines have become increasingly important over the last years. Twenty-seven per cent of pharmaceutical sales in Europe come from biological medicines. This market grew by 5.5% vs. a total market growth of 1.9% in value sales between 2012 and 2013. Many of Europe's top selling biologic molecules are facing patent expiry by 2020[1]. Most biological medicines come at a high cost and governments have difficulty in coping with these costs in their constrained pharmaceutical budgets, especially in current times of austerity. To date, biosimilars account for less than 0.5% of the $221 billion market of biological medicines worldwide. Biosimilars can bring huge savings for payers, and will increase the access to medicines for patients who could not otherwise afford treatment[2]. Figure 1 The biologics Market - IMS Health Thought Leadership, September 2013 Governments must realize that biosimilar medicines are different to generic medicines and as such a unique approach is needed. By applying the generic pricing model to biosimilar medicines, governments risk marking the biosimilar market unsustainable and patients and payers will no longer benefit.

Abstract 2390: The normal brain microenvironment reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization

Abstract Towards developing a model system for investigating the role of the microenvironment in the radioresistance of glioblastoma (GBM), human glioblastoma stem-like cells (GSCs) were grown in co-culture with human astrocytes. Using a trans-well assay, survival analyses showed that astrocytes significantly decreased the radiosensitivity of GSCs compared to standard culture conditions, yet had no effect on the established cell line U251. The critical lesion mediating radiation-induced cell death is the DNA double-strand break (DSB). Because γH2AX nuclear foci correspond to radiation-induced DSBs and their dispersal correlates with DSB repair, we determined the initial level of radiation-induced γH2AX foci in GSCs cultured with or without astrocytes. In irradiated co-cultures, the initial level of radiation-induced γH2AX foci was reduced and foci dispersal was enhanced suggesting that the presence of astrocytes influenced the induction and repair of DNA DSBs. These findings indicate that astrocytes can decrease the radiosensitivity of GSCs in vitro via a paracrine based mechanism and further support a role for the microenvironment as a determinant of GBM radioresponse. Chemokine profiling of co-culture media identified a number of bioactive molecules not present under standard culture conditions, including IL-6. The gene expression profiles of GSCs grown in co-culture were also significantly different as compared to GSCs grown alone. For the GSC transcripts increased after co-culture with astrocytes 6 biological functions (containing at least 45 molecules) were identified including Cell Death and Survival, which contained signaling molecules previously associated with radioresponse. Further, pathway analysis identified multiple upstream regulators of affected transcripts that were significantly increased in co-culture. The top regulator molecule was IL-6, which was consistent with elevated levels of this cytokine in co-culture media. Additional upstream regulators included cytokines and growth factors, consistent with a paracrine based effect of astrocytes on GSC gene expression, as well as the transcription factors NFκB and STAT3, which are subject to regulation by cytokines/growth factors. These analyses were consistent with an astrocyte mediated modification in GSC phenotype and moreover, suggested a number of potential targets for GSC radiosensitization that were unique to co-culture conditions. Along these lines, STAT3 was activated in GSCs grown with astrocytes; the JAK/STAT3 inhibitor WP1066 enhanced the radiosensitivity of GSCs under co-culture conditions and when grown as orthotopic xenografts. These data further suggest that this co-culture system may also provide an approach for identifying additional targets for GBM radiosensitization. Citation Format: Barbara Helen Rath, Amy Wahba, Kevin Camphausen, Philip Tofilon. The normal brain microenvironment reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2390. doi:10.1158/1538-7445.AM2015-2390

Novel Non-Peptide Inhibitors against SmCL1 of Schistosoma mansoni: In Silico Elucidation, Implications and Evaluation via Knowledge Based Drug Discovery.

Schistosomiasis is a major endemic disease known for excessive mortality and morbidity in developing countries. Because praziquantel is the only drug available for its treatment, the risk of drug resistance emphasizes the need to discover new drugs for this disease. Cathepsin SmCL1 is the critical target for drug design due to its essential role in the digestion of host proteins for growth and development of Schistosoma mansoni. Inhibiting the function of SmCL1 could control the wide spread of infections caused by S. mansoni in humans. With this objective, a homology modeling approach was used to obtain theoretical three-dimensional (3D) structure of SmCL1. In order to find the potential inhibitors of SmCL1, a plethora of in silico techniques were employed to screen non-peptide inhibitors against SmCL1 via structure-based drug discovery protocol. Receiver operating characteristic (ROC) curve analysis and molecular dynamics (MD) simulation were performed on the results of docked protein-ligand complexes to identify top ranking molecules against the modelled 3D structure of SmCL1. MD simulation results suggest the phytochemical Simalikalactone-D as a potential lead against SmCL1, whose pharmacophore model may be useful for future screening of potential drug molecules. To conclude, this is the first report to discuss the virtual screening of non-peptide inhibitors against SmCL1 of S. mansoni, with significant therapeutic potential. Results presented herein provide a valuable contribution to identify the significant leads and further derivatize them to suitable drug candidates for antischistosomal therapy.

In-silico structural, virtual screening and docking studies of Human Cytochrome P450 2A7 protein.

Among CYPs, CYP2A sub-family is well known for its function to metabolize xenobiotics. CYP2A includes three members: CYP2A6, CYP2A7 and CYP2A13. Of these three proteins, structure and function of CYP2A6 and CYP2A13 are widely studied whereas very little study has been carried out on CYP2A7. In the initial in vitro studies on CYP2A7, full protein in its active form could not be expressed. The exact structure and function of CYP2A7 is still not revealed. However, up-regulation of CYP2A7 has been reported in malignant oesophageal cells and colon cancer cells. In the present study, we generated the structure of CYP2A7 protein. The modelled proteins were validated and subjected to molecular docking analyses. The energy and RMSD calculations demonstrated that the protein is highly conserved in nature i.e. the protein is not much flexible. Here the ligand molecules of NCI Diversity Set II from the ZINC database against the active site of the CYP2A7 protein were screened. Five compounds that possess good inhibitory activity against CYP2A7 active site were identified. The top ranking molecule (ZINC01572309) has a minimum energy score of -12.0 Kcal/Mol. This compound is thus a good starting point for further development of strong inhibitors. Our in silico approach could help in better structural and functional analysis of CYP2A7. Apart from structural description of CYP2A7, elaboration of binding sites for inhibitors provides us with an opportunity to utilize binding pockets in targeted inactivation of this protein for further research.

Abstract 4173: Discovery at the interface: novel anticancer agents targeting human estrogen receptor/S100 interactions

Abstract Estrogen-triggered nuclear transcription factor, estrogen receptor (ER) is expressed in about 70% of breast cancer. ER mediates various cellular signaling events including the genomic regulation of target genes that affect reproduction, development, and general metabolism. The antiestrogen tamoxifen is currently administered to patients in order to induce regression of the tumor growth. However, upon continued administration, breast cancer patients develop resistance to tamoxifen. In addition, calcium binding proteins such as, calmodulin (CaM) which are significantly overexpressed in cancer cells, can activate transcription of target genes by directly binding to ER in lieu of estrogen. Calmodulin antagonists (w7 and melatonin) have been shown to significantly inhibit human estrogen receptor alpha (hERalpha) transcriptional activity. In search of a novel anti-cancer agent, we generated a library of interaction profiles of human ER-EF hand protein complexes and identified S100B and S100P (high sequence and structure homology with CaM) as potential targets. Furthermore, S100P is shown to mediate tamoxifen-acquired resistance and cell migration capacity in MCF-7 breast cancer cells. Our objective is to develop peptidomimetics and small molecules to block ER-S100 interactions using an integrated proteomics-assisted drug discovery approach. Briefly, using the fold information and contact regions obtained from the FT-ICR mass spectrometry, 3D structures of ER-S100 protein complexes were reconstructed. These structures of ER best represent the conformational state sensed by the specific interacting partner. ER-S100 complex is distinct from CaM. The lack of the connective peptidic region between the EF hand pairs in S100 attributed to less interaction coverage than CaM. The identified ER conformation-sensing regions of the interacting EF hand proteins were used to develop a library of top peptidomimetics and potential small molecule sensors targeting the interfaces of ER-S100 interactions. We have evaluated their ability to block specific ER-S100 interactions in a high throughput fluorescent polarization based screen, to inhibit cancer cell proliferation and ER-mediated transcription of target genes. We believe that the ensemble of ER-EF hand protein complexes generated by our integrated proteomics-assisted protein interaction profiling will shed light on the lingering issue of hormone independent activation of ER at the molecular level and novel therapeutics targeting ER-S100 interactions. Citation Format: David H. Lee, Bethany K. Asare, Matthew L. Hudson, Rajendram V. Rajnarayanan. Discovery at the interface: novel anticancer agents targeting human estrogen receptor/S100 interactions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4173. doi:10.1158/1538-7445.AM2014-4173

Docking and Virtual Screening to Identify PKC Agonists: Potentials in Anticancer Therapeutics

Protein kinase C (PKC) is down-stream to most of the G-protein coupled receptor or tyrosine kinase receptors mediated signaling events from the cell surface. PKC C1 domain has a hydrophobic region with a polar groove to facilitate 1,2-diacyl-glycerol (DAG) binding or other agonist molecule for PKC activation. Post activation, a partial or complete blocking of hydrophilic groove makes the DAG binding site completely hydrophobic and facilitates easier penetration of the PKC into the membrane. Phorbol ester, a strong PKC agonist, uses this mechanism to induce tumor formation. A total of 300 heterocyclic compounds with 70% similarity to phorbol 12-myristate 13-acetate (PMA) were selected, and virtual docking was performed with PKC-α as target. An initial screening indicated that most of the molecules fit well into the C1 domain and had better binding energy than PMA. Further analysis in a PMA competition experiment identified five molecules, Zc 67913417, Zc 68601770, Zc 25726447, Zc 35376386 and Zc 49785214 as potent PKC agonists. In addition, as these compounds showed better binding than PMA, more interaction with PKC residues (hydrogen bonding and hydrophobic), and the top five hit molecules was potent enough to abolish carcinogenic effects of PMA. Searching the top heterocyclic compounds into the drug database gave a number of approved drugs. Testing two candidate drugs, nandrolone decanoate and budesonide, reduced cellular viability of HT1080 in a dose-dependent manner with an IC50 values of 96.8 nM and 200nM respectively. An in silico toxicity analysis indicated that top hit molecules are non-toxic, non-mutagenic in cellular and bacterial system, and have no tumorigenic potentials in a single cell or animal model. Hence, a virtual screening, agonist competition assay, and in silico toxicity assessment allowed us to identify five new PKC agonist molecules for future drug discovery against cancer.

Connectivity maps for biosimilar drug discovery in venoms: The case of Gila Monster Venom and the anti-diabetes drug Byetta®

Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database. As our test animal venom we chose Heloderma suspectum venom (Gila monster) since exendin-4, a glucagon-like peptide 1 receptor agonist, isolated from the venom is currently on the market to treat type 2 diabetes. The action of Byetta® (exentide, synthetic exendin-4), was also used in transcriptome studies. Analysis of transcriptomes from cells treated with the venom or the drug showed similarities as well as differences. The former case was primarily attributed to the fact that Gila monster venom likely contains a variety of biologically active molecules that could alter the MCF7 cell transcriptome compared to that of the single perturbant Byetta®. Using Ingenuity Pathway Analysis software, insulin-like growth factor 1 signaling was identified in the category of “Top Canonical Pathways” for both the venom and Byetta®. In the category of “Top Molecules” up-regulated, both venom and Byetta® shared IL-8, cyclic AMP-dependent transcription factor 3 (ATF-3), neuron-derived orphan receptor 1 (NR4A3), dexamethasone-induced Ras-related protein 1 (RASD1) and early growth response protein 1, (EGR-1) all with potential relevance in diabetes. Using Connectivity Mapping, Gila monster venom showed positive correlation with 1732 instances and negative correlation with 793 instances in the Connectivity database whereas Byetta® showed positive correlation with 1692 instances and negative correlation with 868 instances. Interestingly, the Gila monster venom and Byetta® both showed positive correlation with the anti-diabetic drugs troglitazone, of the thiazolidinedione class, and metformin, of the biguanide class, although Byetta® as a glucagon-like peptide-1 (GLP-1) agonist functions in a different manner than either of these two classes of anti-diabetic drugs. In summary, despite the fact that Gila monster venom contains a mixture of biologically active molecules, similarities in terms of perturbation of gene expression profiles on MCF7 cells were observed between the venom and the drug Byetta®. Furthermore, using Connectivity Mapping the Gila monster venom was demonstrated to have nodes of positive correlation to several anti-diabetic drugs two of which were the same as observed with Byetta®. Therefore, this study suggests that by using this approach novel drug activities heretofore unconsidered may be discovered in venoms using informatic tools and Connectivity Mapping.

Docking studies towards exploring antiviral compounds against envelope protein of yellow fever virus

Yellow fever is among one of the most lethal viral diseases for which approved antiviral therapies were yet to be discovered. Herein, functional assignment of complete YFV proteome was done through support vector machine. Major envelope (E) protein that mediates entry of YFV into host cell was selected as a potent molecular target. Three dimensional structure of the molecular target was predicted using Modeller9v7. The model was optimized in Maestro9.0 applying OPLS AA force field and was evaluated using PROCHECK, ProSA, ProQ and Profile 3D. The BOG pocket residues Val48, Glu197, Thr200, Ile204, Thr265, Thr268 and Gly278 were located in YFV E protein using SiteMap2.3. More than one million compounds of Ligandinfo Meta database were explored using a computational virtual screening protocol targeting BOG pocket of the E protein. Finally, ten top ranked lead molecules with strong binding affinity to BOG pocket of YFV E protein were identified based on XP Gscore. Drug likeliness and comparative bioactivity analysis for these leads using QikProp3.2 had shown that these molecules would have the potential to act as better drug. Thus, the 10 lead molecules suggested in the present study would be of interest as promising starting point for designing antiviral compound against yellow fever.

ChemInform Abstract: The Millimeter-Wave Rotational Spectrum of Tertiary Butyl Isocyanide.

The millimeter-wave rotational spectrum of tertiary butyl isocyanide, (CH3)3CNC, was measured in the ground state and in the first excited state of the doubly degenerate CNC bending mode vβ. Accurate spectroscopic constants for both states have been determined from frequency measurements spanning the range 146–333 GHz. The results are compared with those for tertiary butyl cyanide, for which improved ground state sextic distortion constants are reported. The experimental quartic centrifugal distortion constants and the Coriolis coupling constant ξβ are well reproduced by a rudimentary force field calculation. Coriolis coupling constants for bending modes of linear segments attached to symmetric top C3v molecules based on a tetrahedrally substituted carbon atom are compared and factors responsible for changes in their values are identified and discussed.

Computer Assisted Assignments of Rotationally Resolved Molecular Spectra

A graphically oriented interactive program for assignments of rotationally resolved molecular spectra has been devised. The program functions by grouping spectral lines in term of the second difference principle, and graphing spectral intensity versus frequency in a bar graph of the selected groups, distinguished by color and/or line-type. This allows for easy detection of regular patterns buried in the observed spectrum. Furthermore, it includes a LoomisWood view for assisting in spectral assignments. As an example, the program was applied in assigning the molecular spectrum of the production in the discharge of PCl3 buffered by helium gas, which may belong to several species. The results suggest that the program is highly efficient and quite useful in the assignment and the analysis of molecular spectra, especially those of symmetric top, slightly asymmetric top and linear molecules. The accuracy and efficiency of this program will likely ensure its wide application in the processing of molecular spectra.

Microwave spectrum of two top molecules in the excited states dimethyl ether, dimethyl sulfide, and dimethyl silane

Microwave spectra of dimethyl ether, dimethyl sulfide, and dimethyl silane in the torsionally excited states have been measured. The methyl internal rotations of these molecules were analyzed from the observed multiplets and from the reported multiplets of transitions. The method developed for ethyl silane in the previous paper was extended to equivalent two top molecules. For equivalent two top molecules, apparent barriers of methyl internal rotations obtained from the experiments were corrected by the kinetic and potential cross terms. They are V 3=2645.8±10.0, 2632.4 ± 42.9, 2146.0 ± 13.8, 1651.5 ± 10.1, 1648.0 ± 13.7, and 1649.9 ± 11.8 cal/mol for (CH 3) 2O, (CD 3) 2O, (CH 3) 2S, (CH 3) 2SiH 2, (CH 3) 2SiD 2, and (CH 3) 2SiHD, respectively. The potential cross terms, V 12(1−cos3 α 1)(1−cos3 α 2) terms are negligible for the three molecules, while V ′ 12sin3 α 1sin3 α 2 terms are also very close to zero except those for (CH 3) 2O and (CD 3) 2O which are small but not negligible ( V ′ 12=−124.4,−158.0 cal/mol). The investigations were extended to those of non-equivalent two top species and the corrected barriers of the methyl tops, V 3, are obtained to be 2615.6 ± 8.6 and 2155.0 ± 15.2 cal/mol for CH 3OCD 3 and CH 3SCD 3. The corrected barrier, V 3(CD 3) of CH 3OCD 3, is obtained to be 2634.4 ± 7.1 cal/mol, while that of CH 3SCD 3 cannot be solved due to the lack of the data available.

Effect of collisions on the rotational recurrences in an ensemble of photofragments

The aim of the present work is to study the dynamics of the decay of rotational coherences for ensembles of photofragments in collision environments. To simplify the presentation, we consider linear fragments produced through an impulsive dissociation of planar asymmetric top parent molecules. Adopting the formalism of quantum kinetic equations in the impact approximation, we derive general analytical expressions for the time development of rotational recurrences (RRs). To perform explicit calculations, the Gordon's J- and M- collision models are generalized to describe orientational relaxation under non-equilibrium conditions and implemented for treating different types of encounters. It is demonstrated that (i) collisions and dissociation do not affect the RR period; (ii) the widths and shapes of rotational transients are both dissociation and collision specific; (iii) the rate of decay of RRs is very sensitive to the collision dynamics but is almost independent of the photofragmentation dynamics. It is concluded that monitoring of RRs in collisional ensembles of photoproducts supplies one not only with structural information on the fragments, but also allows one to know about the photofragmentation dynamics and the efficiency of the angular momentum scrambling.

Partial inversion in small molecules: New potentialities for the spectroscopic diagnostics of gases

The formation of vibrational-rotational absorption spectra of small molecules in vibrationally non-equilibrium conditions, with the possibility of manifestation of partial population inversion of levels and negative absorption, is studied. Specific features of the partial inversion in linear and top molecules are analyzed. It is shown that water vapor is the best object among atmospheric gases for the realization of this effect. Formulas for the integrated line intensities and the absorption coefficient of two-and three-level nonequilibrium vibrational systems with a rotational structure are obtained. It is shown that the partial-inversion effect can be used to study weak vibrational-rotational transitions. Concrete calculations for the (000)-(010)-(020) bands of water molecules at different temperatures are made. The frequencies are determined for which negative absorption is the strongest.

Transition-state theory treatment of capture collisions between ions and symmetric top dipolar molecules

Classical microcanonical transition-state theory gives the reduced rate coefficient for the capture of an ion by a symmetric top dipole which is dependent on two dimensionless parameters: ξ, which is defined by molecular constants of the system exclusively and X1 which is additionally defined by energy. Examination of the energy dependence of the microcanonical rate coefficient reveals that at both ξ→ 0 and ξ→∞ the values obtained are larger by ca. 20% than those estimated for the ion–linear dipole capture. However, thermal averaging results in complete removal of this difference. Apparently, the dipole symmetry is of little consequence under the condition of thermal equilibrium.

Analysis of the interaction potential of a molecule physisorbed on NaCl(100) surface

Semi-empirical interaction potentials are used to determine the stable site and the adsorption energy of diatomic (CO) or symmetric top (CH3F) molecules physisorbed on NaCl(100) surface. Within the approximation of harmonic molecular motions and rigid NaCl substrate, the adsorption energy is calculated and compared to experimental values deduced from thermodynamic measurements. The contribution of the electric interaction between the polar molecules and the ionic substrate is dominant since it represents 75% of the total energy.

Torsionally inelastic collisions between a near-symmetric top molecule and a structureless atom

The close-coupling formulation is presented for collisions of a structureless atom with a near-symmetric top exhibiting internal rotation, such as methanol. The molecule is approximated as a symmetric top whose internal rotation axis coincides with the symmetry axis. The K doubling arising from the asymmetry is taken into account only to first order. Both rotational and torsional inelasticity are considered, but the molecule is considered to be rigid with respect to all other vibrational degrees of freedom. Expressions are given for the matrix elements of the interaction potential between any two rotational–torsional states. It is shown that A↔E and E1↔E2 collisional excitation is forbidden. The infinite order sudden (IOS) approximation is extended to systems exhibiting internal rotation by applying the sudden limit to the torsional motion as well as to the overall rotation. Based on the expressions for the IOS cross sections, it is shown that a propensity rule holds for transitions elastic in J or in K between two A± doublets similar to that governing transitions between K doublets in asymmetric top molecules. It is also shown that in the low-barrier limit, torsionally inelastic cross sections depend only on Δn, the change in the angular momentum of the internal rotor, and not on the particular initial and final n. The IOS factorization expression shows that in the low-barrier limit, all of the dynamical information for E↔E transitions is contained in the cross sections for excitation out of the J=0, K=0, υ=0 ground state.

Conformation, barrier to internal rotation, and structure of the PH 2-group in phenylphosphine, studied by microwave spectroscopy

The microwave spectra of phenylphosphine (C 6H 5PH 2) and of mono- and dideuterated phenylphosphine (C 6H 5PHD and C 6H 5PD 2) were investigated. The two torsional sublevels of the vibrational ground state were assigned for each molecular species. Only μ a -and μ b -lines were observed, the μ b -lines being split by approximately twice the splitting of the torsional sublevels. By means of internal rotation calculations with a program that determines the effective Hamiltonian for one top molecules without symmetry restrictions, the twofold barriers to internal rotation were determined to be 94.2 cm −1 (C 6H 5PH 2), 91.1 cm −1 (C 6H 5PHD), and 85.5 cm −1 (C 6H 5PD 2). No effects due to inversion of the PH 2 group were observed in the spectra. For C 6H 5PH 2 and C 6H 5PD 2 the internal rotation potential is of the cos 2γ type with the minimum position corresponding to the configuration with the hydrogen atoms of the phosphine group on opposite sides of the phenyl ring plane, which is thus a plane of symmetry for the molecule. The C 6H 5PHD potential, however, contains an additional sin 2γ term with the effect of rotating the minimum 8.5° in the direction from D toward H. The direct monosubstitution method for determination of the hydrogen atoms of the PH 2 group gave inconsistent results, but the disubstitution method yielded a result comparable to the internal rotation calculation. The structural parameters determined for the PH 2 group are: PH = 1.414 Å, HPH = 94.27°, CPH = 97.29°, and tilt angle (CP to internal rotation axis) = 2.96° (P and H being on opposite sides of the internal rotation axis).