Contrasting packing modes for tubular assemblies in chlorosomes.

The largest light-harvesting antenna in nature, the chlorosome, is a heterogeneous helical BChl self-assembly that has evolved in green bacteria to harvest light for performing photosynthesis in low-light environments. Guided by NMR chemical shifts and distance constraints for Chlorobaculum tepidum wild-type chlorosomes, the two contrasting packing modes for syn-anti parallel stacks of BChl c to form polar 2D arrays, with dipole moments adding up, are explored. Layered assemblies were optimized using local orbital density functional and plane wave pseudopotential methods. The packing mode with the lowest energy contains syn-anti and anti-syn H-bonding between stacks. It can accommodate R and S epimers, and side chain variability. For this packing, a match with the available EM data on the subunit axial repeat and optical data is obtained with multiple concentric cylinders for a rolling vector with the stacks running at an angle of 21° to the cylinder axis and with the BChl dipole moments running at an angle ߠ∼ 55° to the tube axis, in accordance with optical data. A packing mode involving alternating syn and anti parallel stacks that is at variance with EM appears higher in energy. A weak cross-peak at -6 ppm in the MAS NMR with 50 kHz spinning, assigned to C-181, matches the shift of antiparallel dimers, which possibly reflects a minor impurity-type fraction in the self-assembled BChl c.

Parahydrogen-induced polarization allows 2000-fold signal enhancement in biologically active derivatives of the peptide-based drug octreotide.

Octreotide, a somatostatin analogue, has shown its efficacy for the diagnostics and treatment of various types of cancer, i.e., in octreotide scan, as radio-marker after labelling with a radiopharmaceutical. To avoid toxicity of radio-labeling, octreotide-based assays can be implemented into magnetic resonance techniques, such as MRI and NMR. Here we used a Parahydrogen-Induced Polarization (PHIP) approach as a cheap, fast and straightforward method. Introduction of L-propargyl tyrosine as a PHIP marker at different positions of octreotide by manual Solid-Phase Peptide Synthesis (SPPS) led to up to 2000-fold proton signal enhancement (SE). Cell binding studies confirmed that all octreotide variants retained strong binding affinity to the surface of human-derived cancer cells expressing somatostatin receptor 2. The hydrogenation reactions were successfully performed in methanol and under physiologically compatible mixtures of water with methanol or ethanol. The presented results open up new application areas of biochemical and pharmacological studies with octreotide.

Recent advances in the application of parahydrogen in catalysis and biochemistry.

Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI) are analytical and diagnostic tools that are essential for a very broad field of applications, ranging from chemical analytics, to non-destructive testing of materials and the investigation of molecular dynamics, to in vivo medical diagnostics and drug research. One of the major challenges in their application to many problems is the inherent low sensitivity of magnetic resonance, which results from the small energy-differences of the nuclear spin-states. At thermal equilibrium at room temperature the normalized population difference of the spin-states, called the Boltzmann polarization, is only on the order of 10-5. Parahydrogen induced polarization (PHIP) is an efficient and cost-effective hyperpolarization method, which has widespread applications in Chemistry, Physics, Biochemistry, Biophysics, and Medical Imaging. PHIP creates its signal-enhancements by means of a reversible (SABRE) or irreversible (classic PHIP) chemical reaction between the parahydrogen, a catalyst, and a substrate. Here, we first give a short overview about parahydrogen-based hyperpolarization techniques and then review the current literature on method developments and applications of various flavors of the PHIP experiment.