Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer

Over the recent years chirped-pulse, Fourier-transform microwave (CP-FTMW) spectrometers have chan- ged the scope of rotational spectroscopy. The broad frequency and large dynamic range make possible structural determinations in molecular systems of increasingly larger size from measurements of heavy atom (13C, 15N, 18O) isotopes recorded in natural abundance in the same spectrum as that of the parent isotopic species. The design of a broadband spectrometer operating in the 2–8 GHz frequency range with further improvements in sensitivity is presented. The current CP-FTMW spectrometer performance is benchmarked in the analyses of the rotational spectrum of the water heptamer, (H2O)7, in both 2– 8 GHz and 6–18 GHz frequency ranges. Two isomers of the water heptamer have been observed in a pulsed supersonic molecular expansion. High level ab initio structural searches were performed to pro- vide plausible low-energy candidates which were directly compared with accurate structures provided from broadband rotational spectra. The full substitution structure of the most stable species has been obtained through the analysis of all possible singly-substituted isotopologues (H218O and HDO), and a least-squares rm(1) geometry of the oxygen framework determined from 16 different isotopic species compares with the calculated O–O equilibrium distances at the 0.01 Å level

Planarizing cytosine: The S 1 state structure, vibrations, and nonradiative dynamics of jet-cooled 5,6-trimethylenecytosine

We measure theS0→S1spectrum and time-resolvedS1state nonradiative dynamics of the “clamped”cytosine derivative 5,6-trimethylenecytosine (TMCyt) in a supersonic jet, using two-color resonanttwo-photon ionization (R2PI), UV/UV holeburning, and ns time-resolved pump/delayed ionization.The experiments are complemented with spin-component scaled second-order approximate cou-pled cluster (SCS-CC2), time-dependent density functional theory, and multi-state second-orderperturbation-theory (MS-CASPT2)ab initiocalculations. While the R2PI spectrum of cytosine breaksoff∼500 cm1above its 000band, that of TMCyt extends up to +4400 cm1higher, with over a hun-dred resolved vibronic bands. Thus, clamping the cytosine C5–C6bond allows us to explore theS1state vibrations andS0→S1geometry changes in detail. The TMCytS1state out-of-plane vibra-tionsν′1,ν′3, andν′5lie below 420 cm1, and the in-planeν′11,ν′12, andν′23vibrational fundamentalsappear at 450, 470, and 944 cm1.S0→S1vibronic simulations based on SCS-CC2 calculationsagree well with experiment if the calculatedν′1,ν′3, andν′5frequencies are reduced by a factorof 2–3. MS-CASPT2 calculations predict that the ethylene-typeS1S0conical intersection (CI)increases from +366 cm1in cytosine to>6000 cm1in TMCyt, explaining the long lifetime andextendedS0→S1spectrum. The lowest-energyS1S0CI of TMCyt is the “amino out-of-plane”(OPX) intersection, calculated at +4190 cm1. The experimentalS1S0internal conversion rateconstant at theS1(v′=0) level iskIC=0.98–2.2·108s1, which is∼10 times smaller than in1-methylcytosine and cytosine. TheS1(v′=0) level relaxes into theT1(3ππ∗) state by intersystemcrossing withkISC=0.41–1.6·108s1. TheT1state energy is measured to lie 24 580±560 cm1above theS0state. TheS1(v′=0) lifetime isτ=2.9 ns, resulting in an estimated fluorescencequantum yield ofΦfl=24%. Intense two-color R2PI spectra of the TMCyt amino-enol tautomersappear above 36 000 cm1. A sharpS1ionization threshold is observed for amino-keto TMCyt,yielding an adiabatic ionization energy of 8.114±0.002 eV

Gas-Phase Cytosine and Cytosine-N 1 -Derivatives Have 0.1–1 ns Lifetimes Near the S 1 State Minimum

Ultraviolet radiative damage to DNA is inefficient because of the ultrafast S1 ⇝ S0 internal conversion of its nucleobases. Using picosecond pump–ionization delay measurements, we find that the S1(1ππ*) state vibrationless lifetime of gas-phase keto-amino cytosine (Cyt) is τ = 730 ps or ∼700 times longer than that measured by femtosecond pump–probe ionization at higher vibrational excess energy, Eexc. N1-Alkylation increases the S1 lifetime up to τ = 1030 ps for N1-ethyl-Cyt but decreases it to 100 ps for N1-isopropyl-Cyt. Increasing the vibrational energy to Eexc = 300–550 cm–1 decreases the lifetimes to 20–30 ps. The nonradiative dynamics of S1 cytosine is not solely a property of the amino-pyrimidinone chromophore but is strongly influenced by the N1-substituent. Correlated excited-state calculations predict that the gap between the S2(1nOπ*) and S1(1ππ*) states decreases along the series of N1-derivatives, thereby influencing the S1 state lifetime

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA