Remote Proton Research Articles

Remote proton elimination: C-H activation enabled by distal acidification.

Generally, the acidity of carbon-hydrogen bonds is most sensitive to functionality just one or two bonds away. Here, we present an approach to the formation of carbon-carbon σ bonds by remote proton elimination, a distinct mode of carbon-hydrogen activation enabled by distal acidification through five carbon-carbon bonds. Application of remote proton elimination to cyclodecyl cations unveiled an appealing method for the synthesis of decalins. The transformation is regioconvergent, proceeds without the need for a directing group or precious metal, and demonstrates exquisite site selectivity. An in-depth computational study illuminated the reaction mechanism. Additionally, we describe the complete stereoisomeric enrichment of the decalin products through epimerization mediated by hydrogen atom transfer.

Detection of remote proton-nitrogen correlations by 1H-detected 14N overtone solid-state NMR at fast MAS.

Detecting proton and nitrogen correlations in solid-state nuclear magnetic resonance (NMR) is important for the structural determination of biological and chemical systems. Recent advances in proton detection-based approaches under fast magic-angle spinning have facilitated the detection of 1H-14N correlations by solid-state NMR. However, observing remote 1H-14N correlations by these approaches is still a challenge, especially for 14N sites having large quadrupolar couplings. To address this issue, we introduce the 1H-14N overtone continuous wave rotational-echo saturation-pulse double-resonance (1H-14N OT CW-RESPDOR) sequence. Unlike regular 2D correlation experiments where the indirect dimension is recorded in the time domain, the 1H-14N OT CW-RESPDOR experiment is directly observed in the frequency domain. A set of 1H-14N OT CW-RESPDOR filtered 1H spectra is recorded at varying 14N OT frequencies. Thanks to the selective nature of the 14N OT pulse, the filtered 1H spectra appear only if the 14N OT frequency hits the positions of the 14N OT central band or one of the spinning sidebands. This set of filtered 1H spectra represents a 2D 1H-14N OT correlation map. We have also investigated the optimizable parameters for CW-RESPDOR and figured out that these parameters are not strictly needed for our working magnetic field of 14.1 T. Hence, the experiment is easy to set up and requires almost no optimization. We have demonstrated the experimental feasibility of 1H-14N OT CW-RESPDOR on monoclinic L-histidine and L-alanyl L-alanine. The remote 1H-14N correlations have been efficiently detected, no matter how large the 14N quadrupolar interaction is, and agree with the crystal structures. In addition, based on the remote 1H-14N correlations from the non-protonated 14N site of L-histidine, we can unambiguously distinguish the orthorhombic and monoclinic forms.

N-C Axially Chiral Anilines: Electronic Effect on Barrier to Rotation and A Remote Proton Brake.

N-Aryl-N-methyl-2-tert-butyl-6-methylaniline derivatives exhibit a rotationally stable N-C axially chiral structure and the rotational barriers around an N-C chiral axis increased with the increase in electron-withdrawing character of para-substituent on the aryl group. X-ray crystal structural analysis and the DFT calculation suggested that the considerable change of the rotational barriers by the electron effect of para-substituents is due to the disappearance of resonance stabilization energy caused by the twisting of para-substituted phenyl group in the transition state. This structural property of the N-C axially chiral anilines was employed to reveal a new acid-decelerated molecular rotor caused by the protonation at the remote position (remote proton brake).

Improving Proton Therapy Accessibility Through Seamless Electronic Integration of Remote Treatment Planning Sites

Proton radiotherapy is a relatively scarce treatment modality in radiation oncology, with only nine centers currently operating in the United States. Funded by Public Law 107-248, the University of Pennsylvania and the Walter Reed Army Medical Center have developed a remote proton radiation therapy solution with the goals of improving access to proton radiation therapy for Department of Defense (DoD) beneficiaries while minimizing treatment delays and time spent away from home/work (time savings of up to 3 weeks per patient). To meet both Health Insurance Portability and Accountability Act guidelines and the more stringent security restrictions imposed by the DoD, our program developed a hybrid remote proton radiation therapy solution merging a CITRIX server with a JITIC-certified (Joint Interoperability Test Command) desktop videoconferencing unit. This conduit, thoroughly tested over a period of 6 months, integrates both institutions' radiation oncology treatment planning infrastructures into a single entity for DoD patients' treatment planning and delivery. This telemedicine solution enables DoD radiation oncologists and medical physicists the ability to (1) remotely access a proton therapy treatment planning platform, (2) transfer patient plans securely to the University of Pennsylvania patient database, and (3) initiate ad-hoc point-to-point and multipoint videoconferences to dynamically optimize and validate treatment plans. Our robust and secure remote treatment planning solution grants DoD patients not only access to a state-of-the-art treatment modality, but also participation in the treatment planning process by Walter Reed Army Medical Center radiation oncologists and medical physicists. This telemedicine system has the potential to lead to a greater integration of military treatment facilities and/or satellite clinics into regional proton therapy centers.

Electronic Integration of Radiation Oncology Clinics via Remote Proton Radiotherapy Telemedicine Solution

Proton radiotherapy is an exciting new modality in radiation oncology, but only a limited number of facilities currently exist in the United States. The costs involved in opening new facilities are significant and the most beneficial uses of proton radiotherapy have yet to be fully determined in clinical trials. Since 2006, the Radiation Oncology Services of the University of Pennsylvania (Penn) and the Walter Reed Army Medical Center have been developing a remote planning system with the goals of 1) improving access to proton radiation therapy for Department of Defense (DoD) patients, 2) minimizing treatment delays and time spent away from home/work (net time savings estimated at one to three weeks per patient), and 3) eliminating the need to duplicate activities at both sites, such as re-staging. This telemedicine solution will facilitate the evaluation of eligibility for and enrollment in protocols at the local level. Initially developed over Internet2, our prototype was migrated to the hospitals' Local Area Networks so as to integrate seamlessly into our existing clinical infrastructure and to meet the stringent security restrictions imposed by the DoD. After evaluating multiple products, we designed a hybrid system merging a CITRIX client with a desktop videoconferencing unit. Although several web-based solutions were initially considered, none were HIPAA-certified. For audio-video interaction, the three principle variables considered were cost, image quality (resolution and frame rates) and assimilation into our existing infrastructure. The CITRIX approach allows us to 1) access remotely a proton therapy calculation engine for treatment planning, 2) transfer patient plans securely to the Penn patient database, and 3) collaborate dynamically to optimize and validate treatment plans. The evaluation of a Tandberg 1700-based prototype system evolved over a period of 12 months, during which the capabilities to conduct ad-hoc and scheduled multi-site video conferences were validated. We believe that this system is a robust, secure, and cost-effective solution that allows greater power and flexibility in the integration of satellite clinics into regional proton therapy centers. Through this integration, proton radiotherapy can be made more widely available and more patients can be enrolled in clinical trials so as to best take advantage of its potential benefits.

Development of a Remote Proton Radiation Therapy Solution over Internet2

Through our existing partnership, our research program has leveraged the benefits of proton radiation therapy through the development a robust telemedicine solution for remote proton therapy planning. Our proof-of-concept system provides a cost-effective and functional videoconferencing desktop platform for both ad-hoc and scheduled communication, as well as a robust interface for data collaboration (application-sharing of a commercial radiation treatment planning package). Over a 2-year period, our evaluation of this model has highlighted the inherent benefits of this affordable remote treatment planning solution, i.e., (1) giving physicians the ability to remotely participate in refining and generating proton therapy plans via a secure and robust Internet2 VPN tunnel to the University of Pennsylvania's commercial proton treatment planning package; (2) allowing cancer-care providers sending patients to a proton treatment facility to participate in treatment planning decisions by enabling referring or accepting providers to initiate ad-hoc, point-to-point communication with their counterparts to clarify and resolve issues arising before or during patient treatment; and thus (3) allowing stewards of an otherwise highly centralized resource the ability to encourage wider participation with and referrals to sparsely located proton treatment centers by adapting telemedicine techniques that allow sharing of proton therapy planning services. We believe that our elegant and very affordable approach to remote proton treatment planning opens the door to greater worldwide referrals to the scarce resource of proton treatment units and wide-ranging scientific collaboration, both nationally and internationally.

Regioselectivity in photocyclization of 2-( N, N-dialkylamino)- and 2-( N-alkylanilino)ethyl benzoylformates via remote proton transfer

Upon irradiation 2-( N, N-dialkylamino)- and 2-( N-alkylanilino)ethyl benzoylformates 1 underwent photocyclization via ζ-hydrogen transfer to ketone carbonyl oxygen from charge-transfer states to give seven-membered azalactones 2 and/or 2′. The ζ-hydrogen transfer occurred regioselectively. Neither Type II products produced via γ-hydrogen trasnfer nor five-membered aminolactones produced via δ-hydrogen transfer could be detected.

ChemInform Abstract: Photocyclization of 2‐(Alkylthio)ethyl Benzoylacetates via Remote Proton Transfer Following Charge‐Transfer Interaction Between Excited Ketone Carbonyl and Thioether Chromophore.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Photocyclization of 2-(alkylthio)ethyl benzoylacetates via remote proton transfer following charge-transfer interaction between excited ketone carbonyl and thioether chromophore

Upon irradiation, 2-(alkylthio)ethyl benzoylacetates 1a–d undergo photocyclization to give eight-membered thia lactones 2. No photoreactivity is observed for 2-(benzylsulfonyl)ethyl benzoylacetate 1e the sulfur atom of which lacks lone pairs able to serve as donor electrons. The photocyclization takes place via 1,9-proton transfer following intramolecular charge-transfer interaction between the sulfur atom and the excited carbonyl group.

Photocyclization of 2-(dialkylamino)ethyl acetoacetates: Remote proton transfer and Stern-Volmer quenching kinetics in the system involving two reactive excited states

Upon irradiation, 2-(dibenzylamino)ethyl and 2-(N-benzyl-N-methylamino)ethyl acetoacetate (1a and 1b) undergo photocyclization via remote proton transfer from the benzyl group to the acetyl carbonyl oxygen to give eight-membered azalactones. Irradiation of the corresponding (diisopropylamino)- and (dimethylamino)ethyl esters gave no azalactones. Introduction of the methyl group on C-2 of 1a brought about a complicated photoreaction, probably due to competition of α-cleavage. The Stern-Volmer plots for the photoreaction of 1a did not show the linear relationship, indicating that the photoreaction proceeds from two reactive excited states. The Stern-Volmer quenching equation for the system was obtained by applying the steady-state approximation and was used for the analysis of the photoreaction of 1a. The triplet lifetime was determined to be 1·6 × 10−8 s.

Unstable Intermediates in X-Irradiated Clathrate Hydrates: ESR and ENDOR of Tetramethylammonium Hydroxide Pentahydrate (TMNOH)

X-irradiation of tetramethylammonium hydroxide pentahydrate (TMNOH) at 77 K produces trapped electrons, and CH3• and (CH3)3N+CH2• radicals. The trapped electrons were detected by bleaching with visible light and by subtraction of spectra from bleached and unbleached samples. The decay of the methyl radicals starts at ≈100 K and that of the (CH3)3N+CH2• radicals at ≈150 K. The ESR spectrum measured at 130 K has the best resolution and is a superposition of contributions from the methyl radicals (13%) and from the (CH3)3N+CH2• radical (87%). The reversibility of the line shapes with temperature variations suggested that the increased resolution observed at 130 K is due to dynamical effects involving the (CH3)3N+CH2• radicals. ESR spectra from these radicals can be simulated by assuming that the hyperfine tensor components for the two α protons are averaged by two types of motions: rotation of the CH2 group about the C2v symmetry axis and precession or wobbling of this axis. The parameters used in the simulation are giso = 2.0022, two equivalent α protons with axial hyperfine components A∥av = 25.0 G and A⊥av = 23.0 G, one 14N nucleus with AN = 3.9 G, and one remote proton with AH,remote = 4.2 G. The remote proton is identified with a lattice proton. If the precession model is adopted, the precession angle calculated from the principal values of the hyperfine tensor for the α protons used in the simulations is 47°. For the wobbling model, the wobbling angle deduced is 72°. These results suggest that the hydrogen-bonded cage around the guest allows large-scale dynamical effects even at 130 K.

1H NMR analysis and conformation of bis-tetrahydrofurans related to annonaceous acetogenins

1H NMR analysis of diastereoisomeric bis-tetrahydrofuran compounds reveals interesting changes in their conformation due to stereoelectronic effect and intramolecular hydrogen bonding. This is particularly demonstrated in one case ( 7) by anisotropic shielding of a remote anomeric proton by a phenyl group.

A new method to distinguish between direct and remote signals in proton-relayed X,H correlations

Inverse heteronuclear multiple-quantum coherence (HMQC) and heteronuclear single-quantum coherence (HSQC) proton-relayed ‘H,X correlation experiments ( l3) using a TOCSY proton transfer (4, 5) have been introduced to obtain information about carbon connectivities. In these spectra it is usually rather difficult to differentiate between the signals of protons attached directly to 13C and the relayed signals. This paper introduces an expanded inverse proton-relayed HSQC correlation sequence in which a delay 26 has been inserted after the proton spin lock to achieve phase discrimination between direct and remote correlation signals (Fig. 1). A product-operator calculation (6) shows the basic idea of this experiment, where I* represents protons directly attached to 13C, I represents remote proton spins, and S represents the 13C spin. The first 90,” (I) pulse creates I* magnetization: 61 = -z:,.

Relayed coherence transfer spectroscopy of heteronuclear systems: detection of remote nuclei in NMR

Heteronuclear two-dimensional NMR experiments are presented which allow the correlation of nuclei that are not directly coupled but belong to a common coupling network. The techniques involve two or more consecutive coherence transfer steps. The applications discussed include the indirect observation of remote proton signals through phosphorus-31 and carbon-13 detection.