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Introduction: This study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells., Methods: Dynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both in vitro and in vivo . Antibody uptake in tumors was visualized through positron emission tomography (PET) imaging. PD-L1 glycosylation status was determined via Western blot analyses before and after PNGase F treatment., Results: Consistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared to atezolizumab, confirmed by in vivo PET imaging and ex vivo biodistribution analyses. Notably, PD-L1 glycosylation at approximately 50 kDa was observed, with PNGase F treatment inducing a shift to 35 kDa in molecular weight. Tissue samples from patient-derived xenografts (PDXs) validated the presence of both glycosylated and deglycosylated PD-L1 (degPD-L1) forms in gastric cancer. Immunofluorescence microscopy and binding assays demonstrated enhanced avelumab binding post-deglycosylation., Discussion: This study provides an understanding of dynamic and spatially heterogeneous PD-L1 expression in gastric cancer. Anti-PD-L1 immunoPET was able to visualize gastric tumors, and PD-L1 glycosylation has significant implications for antibody recognition. These insights contribute to demonstrating the complexities of PD-L1 in gastric cancer, holding relevance for refining PD-L1 imaging-based approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ibrahim, Simó, Brown, Shmuel, Panikar, Benton, DeWeerd, Dehdashti, Park and Pereira.)

The human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are antibody-drug conjugates (ADC) clinically used to treat HER2-positive breast cancer, with the latter receiving clinical approval in 2021 for HER2-positive gastric cancer. Lovastatin, a cholesterol-lowering drug, temporally elevates cell-surface HER2 in ways that enhance HER2-ADC binding and internalization. Methods: In an NCIN87 gastric xenograft model and a gastric patient-derived xenograft model, we used the 89 Zr-labeled or 64 Cu-labeled anti-HER2 antibody trastuzumab to investigate the dosing regimen of ADC therapy with and without coadministration of lovastatin. We compared the ADC efficacy of a multiple-dose ADC regime, which replicates the clinical dose regimen standard, with a single-dose regime. Results: T-DM1/lovastatin treatment inhibited tumor growth, regardless of multiple- or single-dose T-DM1 administration. Coadministration of lovastatin with T-DM1 or T-DXd as a single dose enhanced tumor growth inhibition, which was accompanied by a decrease in signal on HER2-targeted immuno-PET and a decrease in HER2-mediated signaling at the cellular level. DNA damage signaling was increased on ADC treatment in vitro. Conclusion: Our data from a gastric cancer xenograft show the utility of HER2-targeted immuno-PET to inform the tumor response to ADC therapies in combination with modulators of cell-surface target availability. Our studies also demonstrate that statins enhance ADC efficacy in both a cell-line and a patient-derived xenograft model in ways that enable a single-dose administration of the ADC., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Metformin has effects beyond its antihyperglycemic properties, including altering the localization of membrane receptors in cancer cells. Metformin decreases human epidermal growth factor receptor (HER) membrane density. Depletion of cell-surface HER decreases antibody-tumor binding for imaging and therapeutic approaches. Here, we used HER-targeted PET to annotate antibody-tumor binding in mice treated with metformin. Methods: Small-animal PET annotated antibody binding in HER-expressing xenografts on administration of an acute versus a daily dose schedule of metformin. Analyses at the protein level in the total, membrane, and internalized cell extracts were performed to determine receptor endocytosis, HER surface and internalized protein levels, and HER phosphorylation. Results: At 24 h after injection of radiolabeled anti-HER antibodies, control tumors had higher antibody accumulation than tumors treated with an acute dose of metformin. These differences were temporal, and by 72 h, tumor uptake in acute cohorts was similar to uptake in control. Additional PET imaging revealed a sustained decrease in tumor uptake on daily metformin treatment compared with control and acute metformin cohorts. The effects of metformin on membrane HER were reversible, and after its removal, antibody-tumor binding was restored. The time- and dose-dependent effects of metformin-induced HER depletion observed preclinically were validated with immunofluorescence, fractionation, and protein analysis cell assays. Conclusion: The findings that metformin decreases cell-surface HER receptors and reduces antibody-tumor binding may have significant implications for the use of antibodies targeting these receptors in cancer treatment and molecular imaging., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and [ 177 Lu]Lu-trastuzumab-based RLT can enhance the therapeutic efficacy of HER2-targeted RLT in drug-resistant gastric cancers. We demonstrate that lovastatin elevates cell surface HER2 levels and increases the tumor-absorbed radiation dose of [ 177 Lu]Lu-DOTA-trastuzumab. Furthermore, lovastatin-modulated [ 177 Lu]Lu-DOTA-trastuzumab RLT durably inhibits tumor growth and prolongs overall survival in mice bearing NCI-N87 gastric tumors and HER2-positive patient-derived xenografts (PDXs) of known clinical resistance to trastuzumab therapy. Statins also exhibit a radioprotective effect, reducing radiotoxicity in a mice cohort given the combination of statins and [ 177 Lu]Lu-DOTA-trastuzumab. Since statins are commonly prescribed to patients, our results strongly support the feasibility of clinical studies that combine lovastatin with HER2-targeted RLT in HER2-postive patients and trastuzumab-resistant HER2-positive patients.

Exceptional surface enhanced Raman scattering (SERS) can be achieved by on-demand mechanisms mediated by the formation of three-dimensional (3D) network supporting hotspots. Herein, a deep eutectic solvent (DES) is used to fabricate plasmonic aerogels as sustainable SERS substrates consisting of different gold nanoparticle (AuNP) heterostructures synthesized in the presence of cellulose nanocrystals (CNCs). This analytical approach is based on the AuNPs 3D arrangement within the CNC matrix, where the transient inter-CNCs interactions collapse after loading with the analyte aqueous solution, forming hotspots on demand. Theoretical calculations support the on-demand SERS mechanism, which consists of the hotspot formation by bringing the AuNPs closer upon activation with the liquid sample loading. To evaluate the plasmonic aerogel performance as a sensing platform, the organophosphorus pesticides edifenphos and parathion were tested in rice and tea extracts. Also, the detection of Methylene Blue in fish muscle extract resulted in a detection limit of 9.8 nM. The results demonstrate that the 3D plasmonic aerogel exhibits significantly higher SERS enhancement and sensitivity when compared to conventional 2D SERS substrates. The use of a green designer solvent, biobased ingredients, and the introduction of on-demand SERS-based sensing pave the way for further developments in the analysis of liquid samples within a sustainable framework.

Resistance mechanisms and heterogeneity in HER2-positive gastric cancers (GC) limit Trastuzumab benefit in 32% of patients, and other targeted therapies have failed in clinical trials. Using patient samples, patient-derived xenografts (PDXs), partially humanized biological models, and HER2-targeted imaging technologies we demonstrate the role of caveolin-1 (CAV1) as a complementary biomarker in GC selection for Trastuzumab therapy. In retrospective analyses of samples from patients enrolled on Trastuzumab trials, the CAV1-high profile associates with low membrane HER2 density and low patient survival. We show a negative correlation between CAV1 tumoral protein levels - a major protein of cholesterol-rich membrane domains - and Trastuzumab-drug conjugate TDM1 tumor uptake. Finally, CAV1 depletion using knockdown or pharmacologic approaches (statins) increases antibody drug efficacy in tumors with incomplete HER2 membranous reactivity. In support of these findings, background statin use in patients associates with enhanced antibody efficacy. Together, this work provides preclinical justification and clinical evidence that require prospective investigation of antibody drugs combined with statins to delay drug resistance in tumors., (© 2022. The Author(s).)

Targeted tumor therapies of receptor tyrosine kinases (RTK) do not work for every patient with cancer, owing to differences in the level of RTK heterogeneity, RTK co-activation mechanisms, and other aspects of disease biology. Over the last years, the combination of non-invasive positron emission tomography (PET) with non-pharmacological doses of an RTK-specific antibody has shown the ability to study cancer biology in real-time and in the whole body of living subjects at the early stages of the disease and in response to therapies. Many RTK-specific antibody-PET imaging conjugates exist in the clinics and show potential for earlier diagnosis and accurate management of oncology patients. Herein, our review concisely focuses on clinical and preclinical data of RTK-targeted PET imaging to detect two significant biological mechanisms of tumor resistance - RTK heterogeneity and RTK co-activation. This mini-review provides an overview of RTK-targeted PET imaging studies of the last 4 years and gives collective information on how it may assist prognostic information and image disease recurrence., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nanobodies (Nb) have a promising future as a part of next generation chemodrug delivery systems. Nb, or VHH, are small (15 kDa) monomeric antibody fragments consisting of the antigen binding region of heavy chain antibodies. Heavy chain antibodies are naturally produced by camelids, however the structure of their VHH regions can be readily reproduced in industrial expression systems, such as bacteria or yeast. Due to their small size, high solubility, remarkable stability, manipulatable characteristics, excellent in vivo tissue penetration, conjugation advantages, and ease of production, Nb have many advantages when compared against their antibody precursors. In this review, we discuss the generation and selection of Nbs via phage display libraries for easy screening, and the conjugation techniques involved in creating target-specific nanocarriers. Furthermore, we provide a comprehensive overview of recent developments and perspectives in the field of Nb drug conjugates (NDCs) and Nb-based drug vehicles (NDv) with respect to antitumor therapeutics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Herein, we report the development of sandwich type Surface Enhanced Raman Spectroscopy (SERS) immunosensor modified to be zwitterionic for the detection of soluble B7-H6 biomarker in blood serum from cervical cancer patients. Anti-fouling capture SERS substrate of biosensor based on gold (Au) thin film was modified with a self-assembled monolayer of zwitterionic l-cysteine to combat serum fouling and was then conjugated with NKp30 receptor protein to capture the B7-H6 biomarker in blood serum. The SERS nanoprobe based on spiky gold nanoparticles (AuNPs) was functionalized with ATP reporter molecule, that is stable at a wide range of pH, making the SERS signal reliable in complex media. Then, it was conjugated with anti-B7-H6 antibody forming the complex anti-B7-H6@ATP@AuNPs (i.e., SERS nanoprobe). The proposed immunosensor demonstrated high reproducibility for the quantitative detection of soluble tumor biomarker B7-H6 within the range of 10 -10  M to 10 -14  M with limit of detection (LOD) of 10 -14  M or 10.8 fg mL -1 , in the cancer patient serum, greatly exceeding (100 fold) the LOD of commercially available ELISA kits. Such low LOD is partially the result of zwitterionic modification which reduces the serum fouling by 55% compared to traditionally used BSA blocked capture substrates (i.e., control). Notably, this immunosensors demonstrated higher accuracy for detecting the B7-H6 biomarker in undiluted blood serum samples from cervical cancer patients and outperforms the currently available analytical techniques, making it reliable for point of care (POC) testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Although great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored., Methods: In this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 was determined using confocal microscopy., Results: Notably, we observed that the addition of sNKp30 to the cervical cancer cell lines decreased tumor cell proliferation and migration rate, but had no effect on apoptosis. We also found that B7-H6 is selectively maintained in tumor cell lines, and that efforts to sort and purify B7-H6 negative or positive cells were futile, as negative cells, when cultured, regained the expression of B7-H6 and B7-H6 positive cells, when sorted and cultivated, lost a percentage of B7-H6 expression., Conclusions: Our results suggest that B7-H6 has an important, as of yet undescribed, role in the biology of the cervical tumor cells themselves, suggesting that this protein might be a promising target for anti-tumor therapy in the future.

Herein, we report the simple and inexpensive approach for the large-scale fabrication of uniform bottom-up Surface Enhanced Raman Spectroscopy (SERS) substrate. SERS substrate was fabricated by controlled sputtering of 10 nm thick gold film on self-assembled silica nanoparticles (SiNPs) of ~120 nm on glass substrates. The SERS detection has been firstly demonstrated using Rhodamine B as a Raman probe molecule with a detection limit of 10 -10  M on Au sputtered SiNPs (i.e., Au@SiNPs). The experimental Raman enhancement from 0 to 6 was achieved on Au@SiNPs due to the generation of multiple SERS hotspot. To combat blood serum fouling, the zwitterionic modification of l-cysteine was done on Au@SiNPs substrates which lowered blood serum fouling by 48%. Our SERS-based sensor demonstrated high reproducibility for the detection of Doxorubicin in undiluted blood serum with a limit of detection of 20 nM, which greatly exceeded the detection range of available methodologies. We envision that the translation of this SERS substrate for the detection of chemo-drugs like Doxorubicin will assist clinicians in making rapid and/or early decisions in patients undergoing sustained chemotherapy to lower its side-effects or to incorporate other treatment methodologies as an option for Personalized treatment., (Copyright © 2020. Published by Elsevier B.V.)

In light of the outbreak of the 2019 novel coronavirus disease (COVID-19), the international scientific community has joined forces to develop effective treatment strategies. The Angiotensin-Converting Enzyme (ACE) 2, is an essential receptor for cell fusion and engulfs the SARS coronavirus infections. ACE2 plays an important physiological role, practically in all the organs and systems. Also, ACE2 exerts protective functions in various models of pathologies with acute and chronic inflammation. While ACE2 downregulation by SARS-CoV-2 spike protein leads to an overactivation of Angiotensin (Ang) II/AT1R axis and the deleterious effects of Ang II may explain the multiorgan dysfunction seen in patients. Specifically, the role of Ang II leading to the appearance of Macrophage Activation Syndrome (MAS) and the cytokine storm in COVID-19 is discussed below. In this review, we summarized the latest research progress in the strategies of treatments that mainly focus on reducing the Ang II-induced deleterious effects rather than attenuating the virus replication., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Published by Elsevier Inc.)

Herein, we reported the fabrication of novel peptide-conjugated ligand-targeted nanoliposomes (LTLs) for chemo-photodynamic therapy against HER2-positive breast cancer. The LTL core was utilized for encapsulating doxorubicin (DOX) for chemotherapy, and methylene blue (MB) attached NaYF 4 :Yb,Er upconversion nanoparticles (UCNPs) for NIR-activated bioimaging and leveraging its visible emission for photoexciting MB for enhanced photodynamic therapy (PDT). The specificity of our LTLs was achieved by conjugating a newly discovered anti-HER2 peptide screened from a phage display peptide library. The high selectivity of the peptide-conjugated LTLs was confirmed by confocal imaging of SKBR-3 (HER2-positive) and MCF-7 (HER2-negative) breast cancer cell lines, illustrating its target-specific nature. The energy transfer from UCNPs to MB was verified, thus enabling the generation of reactive oxygen species upon activation with a 975 nm laser source (0.60 W cm -2 ) under 5 min continuous excitation. A significant decline in the cell viability by 95% was observed using chemo-photodynamic combinational therapy, whereas for chemo-drug alone and PDT alone, the cell proliferation declined by 77% and 84%, respectively. Furthermore, we demonstrated an improved uptake of the LTLs inside a 3D model of SKBR-3 tumor spheroids, where the spheroid cell viability was suppressed by 66% after the use of combinational therapy. Thus, our results suggest great prospective use of theranostic LTLs for breast cancer management.

Photodynamic and immune therapies are innovative medical strategies against cancer, and their integration with upconversion nanoparticles (UCNPs) can improve the diagnosis and treatment of the disease. The UCNPs convert the deep penetrating near-infrared (NIR) light into higher energy emissions, allowing the imaging and detection of malignant cells and the simultaneous energy transfer for activation of the photosensitizers. In this work, the UCNPs were coated with a photocatalytic TiO 2 /ZrO 2 shell and an increase of oxygen defects (V O ) was observed as a result of the partial substitution of Ti 4+ by Zr 4+ ions in the crystalline lattice of TiO 2 . Such defects act as trapping states improving charge separation and then reducing the recombination rate of the electron-hole pairs (e - /h + ) generated upon resonant energy transfer from the donor (UCNPs) to acceptors (shell). The overall results are the enhancement of both ROS production and the emission band centered at 801 nm which is useful for tracking cells at the deep tissue level. However, an excess of those defects produces deleterious effects on both processes as a result of charge migration. The specificity against HER2 positive breast cancer was provided by bioconjugation with the monoclonal antibody trastuzumab. After administration of the synthesized NaYF 4 :Yb,Tm@TiO 2 /ZrO 2 -trastuzumab theranostic nanocomplex doped with an optimal ZrO 2 molar concentration (25%) and subsequent exposure to 975 nm light (0.71 W cm -2 ) during 5 minutes, HER2-positive SKBr3 breast cancer cells were suppressed with 88% drop of the cell viability, 28% higher than UCNPs decorated with a pure TiO 2 shell.

Surface-enhanced Raman spectroscopy (SERS) has recently emerged as an innovative tool for therapeutic-drug monitoring (TDM), making it an ideal candidate for personalized treatment. Herein, we report a layer-by-layer (LbL) approach for the fabrication of a highly reproducible hybrid SERS substrate based on graphene oxide (GO)-supported l-cysteine-functionalized starlike gold nanoparticles (SAuNPs). These designed substrates were utilized for TDM of paclitaxel and cyclophosphamide in blood serum. The SAuNPs' efficient binding at the edges of GO creates a better SERS hotspot with enhanced Raman sensitivity because of the spacing of ∼2.28 nm between the SAuNPs. In addition, the hierarchically modified substrate with a self-assembled monolayer of zwitterionic amino acid l-cysteines acts like a brush layer to prevent SERS-hotspot blockages and fouling by blood-serum proteins. The antifouling nature of the substrate was determined quantitatively by a bichinchonic acid assay using bovine-serum albumin (BSA) as a protein model on the l-cysteine SAuNPs@GO hybrid substrate (the test) and a cysteamine SAuNPs@GO substrate (the control). The l-cysteine SAuNPs@GO hybrid exhibited 80.57% lower BSA fouling compared with that of the cysteamine SAuNPs@GO substrate. The SERS spectra were acquired within 20 s, with detection limits of 1.5 × 10 -8 M for paclitaxel and 5 × 10 -9 M for cyclophosphamide in blood serum. Such sensitivities are 4 times and 1 order of magnitude higher than the currently available sophisticated analytical techniques, which involve high costs with each analysis.

Photodynamic therapy represents a very attractive therapeutic tool considered to be effective, minimally invasive and minimally toxic. However, conventional photodynamic therapy actually has two main constraints: the limited penetration depth of visible light needed for its activation, and the lack of selectivity. Considering this, this work reports the synthesis and evaluation of a novel nanoconjugate for imaging and selective photodynamic therapy against HER2-positive breast cancer, a particularly aggressive form of the disease. It was demonstrated that upon 975 nm near infrared light exposure, the red emission of the NaYF4:Yb,Er up-conversion nanoparticles (UCNPs) can be used for optical imaging and simultaneously represent the source for the excitation of a covalently bound zinc tetracarboxyphenoxy phthalocyanine (ZnPc), a photosensitizer that in turn transfers energy to ground state molecular oxygen to produce cytotoxic singlet oxygen. The specificity of our nanoconjugates was achieved by immunoconjugation with Trastuzumab (Tras), a specific monoclonal antibody for selective detection and treatment of HER2-overexpressing malignant breast cancer cells. Selective tracking of SKBR-3 HER2-positive cells was verified by confocal microscopy analysis, and the photodynamic therapy effect was considerably improved when Trastuzumab was incorporated into the nanoconjugate, the UCNPs-ZnPc-Tras being practically inert in the absence of infrared light exposure but reducing the HER2-positive cell viability up to 21% upon 5 min of the irradiation. This theranostic nanoconjugate represents a valuable alternative for HER2-positive breast cancer imaging and selective photodynamic therapy.

The infrared and Raman spectra (3200-50 cm(-1)) of the gas, liquid or solution, and solid have been recorded of isocyanocyclopentane, c-C5H9NC. FT-microwave studies have also been carried out and 23 transitions were recorded for the envelope-axial (Ax) conformer. Variable temperature (-65 to -100 °C) studies of the infrared spectra (3200-400 cm(-1)) dissolved in liquid xenon have been carried out. From these data, both the Ax and envelope-equatorial (Eq) conformers have been identified and their relative stabilities obtained. The enthalpy difference has been determined to be 102±10 cm(-1) (1.21±0.11 kJ mol(-1)) with the Ax conformer the more stable form. The percentage of the Eq conformer is estimated to be 38±1% at ambient temperature. The conformational stabilities have been predicted from ab initio calculations by utilizing several different basis sets up to aug-cc-pVTZ from both MP2(full) and density functional theory calculations by the B3LYP method. Vibrational assignments have been made for the observed bands for both conformers with initial predictions by MP2(full)/6-31G(d) ab initio calculations to obtain harmonic force constants, wavenumbers, infrared intensities, Raman activities and depolarization ratios for both conformers. The structural parameter values for the Ax form are; for the heavy atom distances (Å): C≡N = 1.176 (3); Cα-N=1.432 (3); Cα-Cβ,Cβ'=1.534 (3); Cβ-Cγ,Cγ'=1.542 (3); Cγ-Cγ'=1.554 (3) and angles (°):∠Cα-N≡C=177.8 (5); ∠CβCα-N=110.4 (5);

The infrared (3500-80 cm(-1)) and Raman spectra (3500-40 cm(-1)) of gas/or liquid and solid (CH(3))(2)PX with X=H (DMH), CN (DMCN) and Cl (DMCl) as well as (CD(3))(2)PH have been recorded and complete vibrational assignments are given for all three molecules. To support the spectroscopic study, ab initio calculations by the Møller-Plesset perturbation method to second order MP2(full) and density functional theory calculations by the B3LYP method have been carried out. The infrared intensities, Raman activities, vibrational frequencies and band contours have been predicted from MP2(full)/6-31G(d) calculations and these theoretical quantities are compared to experimental ones when available. By utilizing the previously reported microwave rotational constants for DMH and DMCN along with the MP2(full)/6-311+G(d,p) predicted values, adjusted r(0) structural parameters for DMH and DMCN have been determined. The heavy atom parameters for DMH are: r(0)(P-C(3,4))=1.8477(30)Å, ∠CPC=99.88(50)° and for DMCN: r(0)(N-C)=1.159(3), r(0)(C-P)=1.790(3), r(0)(P-C(4,5))=1.841(3)Å, ∠NCP=175.7(5), ∠CPC(4,5)=97.9(5) and ∠CPC=100.7(5)°. Barriers to internal rotation are reported. The experimental values are compared to the corresponding values of some similar molecules whenever possible., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The infrared spectra (3500-220 cm(-1)) of cyclobutylgermane, c-C(4)H(7)GeH(3) have been recorded of the gas. Also variable temperature (-65 to -100 °C) studies of the infrared spectra (3500-400 cm(-1)) of the sample dissolved in liquid xenon were recorded and both the equatorial and axial conformers were identified. The enthalpy difference has been determined from 10 band pairs 8 temperatures to give 112 ± 11 cm(-1) (1.34 ± 0.13 kJ mol(-1)) with the equatorial conformer the more stable form. The percentage of the axial conformer present at ambient temperature is estimated to be 37 ± 1%. From ab initio calculations conformational stabilities have been predicted from both MP2(full) and density functional theory calculations from a variety of basic sets. The r(0) structure parameters have been obtained for both conformers from the previously reported rotational constants from the three isotopologues. The determined heavy atom distances for the equatorial [axial] form are (Å) Ge-C(α)=1.952(3) [1.950(3)], [Formula: see text] , [Formula: see text] [1.551(3)] and angles in degrees (°) ∠GeC(α)C(β)=118.6(5) [113.4(5)], [Formula: see text] , ∠C(α)C(β)C(γ)=87.8(5) [88.8(5)], [Formula: see text] and a puckering angle of 29.1(5) [25.1(5)]. Data from ab initio calculations were used to predict vibrational harmonic force constants, fundamental wavenumbers, infrared intensities, Raman activities and depolarization ratios for both conformers. The results are compared to the corresponding properties of some related molecules., (Copyright © 2012. Published by Elsevier B.V.)

The infrared spectra of gaseous and solid N-bromo-hexafluoro-2-propanimine, (CF(3))(2)CNBr, have been obtained from 2000 to 50 cm(-1). The vibrational assignment for the normal modes is proposed based on infrared band contours, group frequencies and normal coordinate calculations utilizing C(s) symmetry. The structural parameters have been obtained from ab initio MP2(full)/6-311+G(d,p) calculations employing the Gaussian-03 program. Additionally, the frequencies and potential energy distributions for the normal modes have been calculated with the MP2(full)/6-31G(d). All of these results are compared to the corresponding data for some similar molecules., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The microwave spectrum (6500-18 ,500 MHz) of 1-fluoro-1-silacyclopentane, c-C(4)H(8)SiHF has been recorded and 87 transitions for the (28)Si, (29)Si, (30)Si, and (13)C isotopomers have been assigned for a single conformer. Infrared spectra (3050-350 cm(-1)) of the gas and solid and Raman spectrum (3100-40 cm(-1)) of the liquid have also been recorded. The vibrational data indicate the presence of a single conformer with no symmetry which is consistent with the twist form. Ab initio calculations with a variety of basis sets up to MP2(full)/aug-cc-pVTZ predict the envelope-axial and envelope-equatorial conformers to be saddle points with nearly the same energies but much lower energy than the planar conformer. By utilizing the microwave rotational constants for seven isotopomers ((28)Si, (29)Si, (30)Si, and four (13)C) combined with the structural parameters predicted from the MP2(full)/6-311+G(d,p) calculations, adjusted r(0) structural parameters have been obtained for the twist conformer. The heavy atom distances in Å are: r(0)(SiC(2)) = 1.875(3); r(0)(SiC(3)) = 1.872(3); r(0)(C(2)C(4)) = 1.549(3); r(0)(C(3)C(5)) = 1.547(3); r(0)(C(4)C(5)) = 1.542(3); r(0)(SiF) = 1.598(3) and the angles in degrees are: [angle]CSiC = 96.7(5); [angle]SiC(2)C(4) = 103.6(5); [angle]SiC(3)C(5) = 102.9(5); [angle]C(2)C(4)C(5) = 108.4(5); [angle]C(3)C(5)C(4) = 108.1(5); [angle]F(6)Si(1)C(2) = 110.7(5); [angle]F(6)Si(1)C(3) = 111.6(5). The heavy atom ring parameters are compared to the corresponding r(s) parameters. Normal coordinate calculations with scaled force constants from MP2(full)/6-31G(d) calculations were carried out to predict the fundamental vibrational frequencies, infrared intensities, Raman activities, depolarization values, and infrared band contours. These experimental and theoretical results are compared to the corresponding quantities of some other five-membered rings., (© 2012 American Institute of Physics)

Infrared and Raman spectra (3500-60 cm(-1)) of gas and/or liquid and solid 1-bromo-1-silacyclopentane (c-C4H8SiBrH) have been recorded and the vibrational data indicate the presence of a single conformer with no symmetry which is consistent with the twisted form. Ab initio calculations with a variety of basis sets up to MP2(full)/6-311+G(2df,2pd) predict the envelope-axial and envelope-equatorial conformers to be saddle points with nearly the same energies but approximately 900 cm(-1) (5.98 kJ/mol) lower in energy than the planar conformer. Density functional theory calculations by the B3LYP method predict slightly lower energies for the two envelope forms and considerably lower energy for the planar form compared to the MP2 predictions. By utilizing the MP2(full)/6-31G(d) calculations the force constants, frequencies, infrared intensities, band contours, Raman activities, and depolarization values have been obtained to support the vibrational assignment. Estimated r0 structural parameters have been obtained from adjusted MP2(full)/6-311+G(d,p) calculations. These experimental and theoretical results are compared to the corresponding quantities of some other five-membered rings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The infrared spectra of gaseous and variable-temperature liquid xenon solutions of pyrrolidine have been recorded. The enthalpy difference has been determined to be 109 ± 11 cm(-1) (1.30 ± 0.13 kJ mol(-1)) with the envelope-equatorial conformer more stable than the twist form with 37 ± 3% present at ambient temperature. Ab initio calculations utilizing various basis sets up to MP2(full)/aug-cc-pVTZ have been used to predict the conformational stabilities, energy at the equatorial-axial saddle point, and barriers to planarity. From previously reported microwave rotational constants along with MP2(full)/6-311+G(d,p) predicted structural values, adjusted r(0) parameters have been obtained for both conformers. Heavy atom distances (Å) of equatorial[twist] conformer are as follows: N(1)-C(2) = 1.469(3)[1.476(3)], N(1)-C(3) = 1.469(3)[1.479(3)], C(2)-C(4) = 1.541(3)[1.556(3)], C(3)-C(5) = 1.541(3)[1.544(3)], C(4)-C(5) = 1.556(3)[1.543(3)]; and angles (deg)∠N(1)C(2)C(4) = 102.5(5)[107.6(5)], ∠N(1)C(3)C(5) = 102.5(5)[105.4(5)], ∠C(2)C(4)C(5) = 104.3(5)[104.6(5)], ∠C(3)C(5)C(4) = 104.3(5)[103.7(5)], ∠C(2)N(1)C(3) = 104.1(5)[103.9(5)], τC(2)C(4)C(5)C(3) = 0.0(5)[13.5(5)]. A complete vibrational assignment is proposed for both conformers.

The microwave spectra of seven isotopomers of fluoromethylsilane, CH(2)FSiH(3), in the ground vibrational state were measured and analyzed in the frequency range 18-40 GHz. The rotational and centrifugal distortion constants were evaluated by the least-squares treatment of the observed frequencies of a- and b-type R- and b-type Q-transitions. The values for the components of the dipole moment were obtained from the measurements of Stark effects from both a- and b-type transitions and the determined values are: |mu(a)| = 1.041(5), |mu(b)| = 1.311(6), and |mu(t)| = 1.674(4) D. Structural parameters have been determined and the heavy atom distances (r(0)) in Angstroms are: Si-C = 1.8942(57) and C-F = 1.4035(55) and the angle in degree, angleSiCF = 109.58(14). A semi-experimental r(e) structure was also determined from experimental ground state rotational constants and vibration-rotation constants derived from ab initio force fields. The internal torsional fundamental, SiH(3), was observed at 149.2 cm(-1) with two accompanying hot bands at 138.8 and 127.5 cm(-1). The barrier to internal rotation was obtained as 717.3(16) cm(-1) (2.051(46) kcal mol(-1)) by combining the analysis of the microwave A and E splittings and the torsional fundamental and hot band frequencies. Ab initio calculations have been carried out with full electron correlation by the second-order perturbation method with several different basis sets up to MP2/6-311+G(d,p) to obtain geometrical parameters, barriers to internal rotation, and centrifugal distortion constants. Adjusted r(0) structural parameters have been obtained by combining the ab initio MP2/6-311+G(d,p) predicted values with the determined rotational constants for the fluoride as well as with the previously reported microwave data for the chloro- and bromo- compounds. These experimental results are compared to the corresponding parameters for the carbon analogues.