Valentin Köhler

Sequential two-photon UV absorption drives efficient pyridine photodissociation from [Ru(tpy)(acac)(py)] ⁺ derivatives in high vacuum.

Optical control of molecular beams is intriguing as it promises to become a new tool for mass spectrometry and quantum interferometry, where a single or two photons deterministically remove a tailored tag from a larger molecular structure, e. g., a polypeptide. This cleavage process can change the charge state of the macromolecule, provide reporting signals for both fragments by mass spectrometry and it can selectively remove the fragments from a molecular beam by the momentum recoil generated in the dissociation process. Here, we explore a series of porphyrin derivatives as candidates for photocleavage in the gas phase. They share a large, conjugated core which promises a high absorption cross section for visible light. We present the individualization and beam formation of candidate molecules and study their photo‐dissociation under tunable, visible radiation. We observe a significant wavelength shift and broadening in the photocleavage cross section for molecules in the gas phase compared to those in solution and we find that a single photon can suffice to trigger the cleavage process.

Controlling the charge state of biomolecules in high vacuum enables experiments in molecular physics and physical chemistry, particularly in applications of mass spectrometry, trapping and cooling, spectroscopy and matter‐wave interferometry. Here we investigate the synthesis, verification and gas phase photolysis of nitrodibenzofuranmethyl aryl ether derivatives. These photocages are chosen because their absorption maximum can be tuned to near 355 nm, where intense pulsed laser light is available. We demonstrate efficient gas‐phase cleavage of a photoactive nitrodibenzofuranmethyl aryl ether derivative, both free and attached to oxytocin. This enables the neutralization of a polypeptide derivative in high vacuum using a wavelength outside the absorption spectrum of natural amino acids.

The configuration at a stereogenic nitrogen center (SNC) determines the spatial organization of a molecule as do stereogenic carbon centers or other stereochemical moieties. The contributions of SNCs to molecular function and their consideration in molecular design are rarely prominently presented. Underlying is the configurational lability of SNCs with a free electron pair and the scarcity of methods for the stereoselective synthesis of compounds with SNCs in general. In this review, we discuss methods to access compounds with configurationally stable SNCs and highlight some of the synthetically most relevant applications. We hope to draw attention to the potential of this stereochemical feature that can be present in diverse compounds such as N-oxides, oxaziridines, haloamines, ammonium ions, metal-bound amines, and constrained amines and amides.1 Introduction2 Some Historical Notes3 Factors That Influence The Nitrogen Inversion Barrier4 Preparation and Isolation of Compounds with Configurationally Stable Stereogenic Nitrogen Centers5 Selected Applications of Compounds with Stereogenic Nitrogen Centers6 Final Remarks

o-Nitrostyryl-pyridinium ions (NSPs) are easily accessible electrophiles that react rapidly and irreversibly with sulfhydryl groups accompanied by a large bathochromic shift.

The isolation of biomolecules in a high vacuum enables experiments on fragile species in the absence of a perturbing environment. Since many molecular properties are influenced by local electric fields, here we seek to gain control over the number of charges on a biopolymer by photochemical uncaging. We present the design, modeling, and synthesis of photoactive molecular tags, their labeling to peptides and proteins as well as their photochemical validation in solution and in the gas phase. The tailored tags can be selectively cleaved off at a well-defined time and without the need for any external charge-transferring agents. The energy of a single or two green photons can already trigger the process, and it is soft enough to ensure the integrity of the released biomolecular cargo. We exploit differences in the cleavage pathways in solution and in vacuum and observe a surprising robustness in upscaling the approach from a model system to genuine proteins. The interaction wavelength of 532 nm is compatible with various biomolecular entities, such as oligonucleotides or oligosaccharides.

The addition of a sulfhydryl group to water-soluble N-alkyl(o-nitrostyryl)pyridinium ions (NSPs) followed by fast and irreversible cyclization and aromatization results in a stable S-Csp2-bond. The reaction sequence, termed Click & Lock, engages accessible cysteine residues under the formation of N-hydroxy indole pyridinium ions. The accompanying red-shift of > 70 nm to around 385 nm enables convenient monitoring of the labeling yield by UV-VIS spectroscopy at extinction coefficients of ≥ 2 × 104 M-1cm-1. The versatility of the linker is demonstrated in the stapling of peptides and the derivatization of proteins, including the modification of reduced Trastuzumab with Val-Cit-PAB-MMAE. The high stability of the linker, fast reaction rates (kapp up to 4.4 M-1s-1 at 20°C), high selectivity, and the bathochromic properties of the Click & Lock reaction provide an appealing alternative to existing methods for cysteine conjugation.

The isolation of biomolecules in high vacuum enables experiments on fragile species in the absence of a perturbing environment. Since many molecular properties are influenced by local electric fields, here we seek to gain control over the number of charges on a biopolymer. Here, we present the design, modelling and synthesis of photoactive molecular tags, their labelling to peptides and proteins as well as their photochemical validation in solution and in the gas phase. The tailored tags can be selectively cleaved off, at a well-defined time and without the need for any external charge transferring agents. The energy of a single or two green photons can already trigger the process and it is soft enough to ensure the integrity of the released biomolecular cargo. We exploit differences in the cleavage pathways in solution and in vacuum, and observe a surprising robustness in upscaling the approach from a model system to genuine proteins. The interaction wavelength of 532 nm is compatible with various biomolecular entities such as oligonucleotides or oligosaccharides.

Most tertiary amines with a stereogenic nitrogen center undergo rapid racemization at room temperature. Consequently, the quaternization of amines under dynamic kinetic resolution seems feasible. N-Methyl tetrahydroisoquinolines are converted into configurationally stable ammonium ions by Pd-catalyzed allylic alkylation. The optimization of conditions and the evaluation of the substrate scope enabled high conversions and an enantiomeric ratio of up to 10:90. We report here the first examples for the enantioselective catalytic synthesis of chiral ammonium ions.

Otto Stern became famous for molecular beam physics, matter-wave research and the discovery of the electron spin, with his work guiding several generations of physicists and chemists. Here we discuss how his legacy has inspired the realization of universal interferometers, which prepare matter waves from atomic, molecular, cluster or eventually nanoparticle beams. Such universal interferometers have proven to be sensitive tools for quantum-assisted force measurements, building on Stern’s pioneering work on electric and magnetic deflectometry. The controlled shift and dephasing of interference fringes by external electric, magnetic or optical fields have been used to determine internal properties of a vast class of particles in a unified experimental framework.