Advances Towards Synthetic Machines at the Molecular and Nanoscale Level

The fabrication of increasingly smaller machines to the nanometer scale can be achieved by either a “top-down” or “bottom-up” approach. While the former is reaching its limits of resolution, the latter is showing promise for the assembly of molecular components, in a comparable approach to natural systems, to produce functioning ensembles in a controlled and predetermined manner. In this review we focus on recent progress in molecular systems that act as molecular machine prototypes such as switches, motors, vehicles and logic operators

Porphyrinic Molecular Devices: Towards Nanoscaled Processes

Abstract: The structural, coordinative, photochemical and electrochemical properties of the porphyrin macrocycle that make them the functional element of choice in ubiquitous biological systems, e.g., chlorophyll, cytochrome P450 and hemoglobin, also contribute to making porphyrins and metalloporphyrins desirable in a “bottom-up ” approach to the construction of nanosized devices. This paper highlights some recent advances in the construction of supramolecular assemblies based on the porphyrin macrocycle that display optically readable functions as a result of photonic or chemical stimuli

Bisporphyrin cavities : from guest complexation to molecular capsule formation

Bisporphyrin cavities : from guest complexation to molecular capsule formatio

Co-polymerization analysis of thermosetting resins using 1 H- 15 N- 13 C triple resonance NMR spectroscopy

1H-15N-13C correlation NMR spectroscopy techniques developed to identify and characterize co-polymer fragments in melamine-urea-formaldehyde (MUF) and phenol-urea-formaldehyde (PUF) model systems have been applied to industrially prepared MUF, PUF, and phenol-melamine-formaldehyde (PMF) resins. The NMR data confirm that co-polymers form in a commercially prepared MUF resin manufactured by Momentive Specialty Chemicals Pty. Ltd. Spectra from PUF model reactions were compared with those from a PUF resin and it was determined that PUF co-polymers did not form in the resin prepared using typical temperature and pH. Finally, NMR spectroscopy was used to identify and characterize PMF co-polymer bonds in a phenol-melamine- urea-formaldehyde (PMUF) resin prepared using a procedure from Momentive Specialty Chemicals Pty. Ltd. With these NMR techniques in hand, it is now possible to relate co-polymer structures to properties of commercial thermosets

Hyperthermophilic Carbamate Kinase Stability and Anabolic In Vitro Activity at Alkaline pH

Carbamate kinases catalyze the conversion of carbamate to carbamoyl phosphate, which is readily transformed into other compounds. Carbamate forms spontaneously from ammonia and carbon dioxide in aqueous solutions, so the kinases have potential for sequestrative utilization of the latter compounds. Here, we compare seven carbamate kinases from mesophilic, thermophilic, and hyperthermophilic sources. In addition to the known enzymes from Enterococcus faecalis and Pyrococcus furiosus, the previously unreported enzymes from the hyperthermophiles Thermococcus sibiricus and Thermococcus barophilus, the thermophiles Fervidobacterium nodosum and Thermosipho melanesiensis, and the mesophile Clostridium tetani were all expressed recombinantly, each in high yield. Only the clostridial enzyme did not show catalysis. In direct assays of carbamate kinase activity, the three hyperthermophilic enzymes display higher specific activities at elevated temperatures, greater stability, and remarkable substrate turnover at alkaline pH (9.9 to 11.4). Thermococcus barophilus and Thermococcus sibiricus carbamate kinases were found to be the most active when the enzymes were tested at 80°C, and maintained activity over broad temperature and pH ranges. These robust thermococcal enzymes therefore represent ideal candidates for biotechnological applications involving aqueous ammonia solutions, since nonbuffered 0.0001 to 1.0 M solutions have pH values of approximately 9.8 to 11.8. As proof of concept, here we also show that carbamoyl phosphate produced by the Thermococcus barophilus kinase is efficiently converted in situ to carbamoyl aspartate by aspartate transcarbamoylase from the same source organism. Using acetyl phosphate to simultaneously recycle the kinase cofactor ATP, at pH 9.9 carbamoyl aspartate is produced in high yield and directly from solutions of ammonia, carbon dioxide, and aspartate.We acknowledge financial support of this work by the Grains Research and Development Corporation (GRDC), the Australian Research Council (ARC), the Australian National University, and CSIRO

Clinical insignificance of [¹⁸F]PSMA-1007 avid non-specific bone lesions: a retrospective evaluation

Purpose: [18F]PSMA-1007 offers advantages of low urinary tracer excretion and theoretical improved spatial resolution for imaging prostate cancer. However, non-specific bone lesions (NSBLs), defined as mild to moderate focal bone uptake without a typical morphological correlate on CT, are a common finding on [18F]PSMA-1007 PET/CT. The purpose of this study was to investigate the clinical outcomes of patients with [18F]PSMA-1007 avid NSBLs, to determine whether patients with NSBLs represent a higher risk clinical cohort, and to determine whether SUVmax can be used as a classifier of bone metastasis. Methods: A retrospective audit of 214 men with prostate cancer was performed to investigate the clinical outcomes of [18F]PSMA-1007 avid NSBLs according to defined criteria. We also compared the serum PSA, Gleason score, and uptake time of patients with [18F]PSMA-1007 avid NSBLs to patients without [18F]PSMA-1007 avid bone lesions. Finally, we analysed an SUVmax threshold to identify bone metastases using ROC curve analysis. Results: Ninety-four of 214 patients (43.9%) demonstrated at least one NSBL. No [18F]PSMA-1007 avid NSBLs met criteria for a likely malignant or definitely malignant lesion after a median 15.8-month follow-up interval (11.9% definitely benign, 50.3% likely benign, and 37.7% equivocal). There were no statistically significant differences in serum PSA, Gleason score, and uptake time between patients with [18F]PSMA-1007 avid NSBLs and those without [18F]PSMA-1007 avid bone lesions. All NSBLs with adequate follow-up had SUVmax ≤ 11.1. The value of the highest SUVmax distinguished between NSBLs and definite prostate cancer bone metastases, whereby an SUVmax threshold of ≥ 7.2 maximized the Youden’s index. Conclusion: [18F]PSMA-1007 avid NSBLs rarely represent prostate cancer bone metastases. When identified in the absence of definite metastatic disease elsewhere, it is appropriate to classify those with SUVmax < 7.2 as likely benign. NSBLs with SUVmax 7.2–11.1 may be classified as equivocal or metastatic, with patient clinical risk factors, scan appearance, and potential management implications used to guide interpretation

Prospective intra-individual blinded comparison of [18F]PSMA-1007 and [68Ga]Ga-PSMA-11 PET/CT imaging in patients with confirmed prostate cancer

Introduction: [18F]PSMA-1007 has potential advantages over [68 Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [18FPSMA-1007 and [68 Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake. Methods: Fifty men (mean age 71.8) were imaged with [68 Ga]Ga-PSMA-11 and [18F]PSMA-1007 < 4 weeks apart. Images were independently reported according to TNM by two experienced nuclear medicine specialists blinded to the other scan and prior imaging. Discordant results were resolved by a third independent nuclear medicine specialist. Quantitative analysis of lesion uptake and physiologic tissue for each tracer was performed by one experienced reader. Results: Scan indications were initial staging (n = 12), biochemical recurrence (n = 27) and metastatic disease evaluation (n = 11). Most patients had ISUP grade group 3 or higher. Median PSA value was 2.7 ng/ml (IQR 0.7–12.0), and a minority of patients (28%) were currently treated with androgen deprivation therapy. [18F]PSMA-1007 uptake was significantly higher than [68Ga]Ga-PSMA-11 in local recurrence, nodal and distant metastases and most physiologic sites (including bone) except for urinary bladder which was significantly lower. [18F]PSMA-1007 upstaged local prostate staging in 5/17 patients, local recurrence in 3/33 patients, regional nodal disease in 3/50 patients and 1 distant metastasis (bladder). [68Ga]Ga-PSMA-11 upstaged regional nodal disease in 1/50 patients and distant metastasis in one patient (right adrenal). Overall AJCC prognostic stage was concordant in 46/50 (92%) patients, with two patients upstaged for both [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 had more equivocal results (one regional node; six equivocal bone lesions, one of which was subsequently confirmed metastatic) than [68Ga]Ga-PSMA-11 (one equivocal local recurrence). Conclusion: Overall AJCC prognostic stage was similar (92%) between [18F]PSMA-1007 and [68Ga]Ga-PSMA-11. [18F]PSMA-1007 demonstrates higher uptake within involved nodes and distant metastases and most physiologic sites except urinary bladder which aided [18F]PSMA-1007 local staging of the prostate primary/local recurrence and regional nodal disease adjacent ureters. However, [18F]PSMA-1007 liver uptake obscured a solitary right adrenal metastasis, and more equivocal bone lesions were identified