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The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are diverse and include variants in numerous ion channels and transporters. Loss-of-function variants in all five endosomal/lysosomal members of the CLC family of Cl- channels and Cl-/H+ exchangers lead to pathology in mice, humans, or both. We have identified nine variants in CLCN3, the gene encoding CIC-3, in 11 individuals with GDD/ID and neurodevelopmental disorders of varying severity. In addition to a homozygous frameshift variant in two siblings, we identified eight different heterozygous de novo missense variants. All have GDD/ID, mood or behavioral disorders, and dysmorphic features; 9/11 have structural brain abnormalities; and 6/11 have seizures. The homozygous variants are predicted to cause loss of ClC-3 function, resulting in severe neurological disease similar to the phenotype observed in Clcn3-/- mice. Their MRIs show possible neurodegeneration with thin corpora callosa and decreased white matter volumes. Individuals with heterozygous variants had a range of neurodevelopmental anomalies including agenesis of the corpus callosum, pons hypoplasia, and increased gyral folding. To characterize the altered function of the exchanger, electrophysiological analyses were performed in Xenopus oocytes and mammalian cells. Two variants, p.Ile607Thr and p.Thr570Ile, had increased currents at negative cytoplasmic voltages and loss of inhibition by luminal acidic pH. In contrast, two other variants showed no significant difference in the current properties. Overall, our work establishes a role for CLCN3 in human neurodevelopment and shows that both homozygous loss of ClC-3 and heterozygous variants can lead to GDD/ID and neuroanatomical abnormalities.

In this work, the ability of different types of nanocages including Al12N12, Al12P12, Be12O12, B12N12, Si12C12, Mg12O12 and C24 for the adsorption and detection of poisonous gases HCN and ClCN has been investigated, theoretically using the D3 dispersion corrected density functional theory (DFT-D3). The absorption spectra of HCN–nanocage and ClCN–nanocage complexes were calculated by the time-dependent density functional theory (TD-DFT) and compared with the calculated absorption spectrum of isolated nanocage to investigate the ability of nanocage for sensing of HCN and ClCN gases. It was found that the strongest interaction between HCN (ClCN) molecule and nanocage takes place when the molecule is adsorbed via its N atom on the surface of nanocage except for C24. Also, it was shown that the Al12N12 is the best adsorbent for HCN and ClCN gases among the selected nanocages and Si12C12 is the best sensor for the detection of these gases using the electroconductivity and absorption spectroscopy techniques. [ABSTRACT FROM AUTHOR]

[Display omitted] • Laser pulse for the dissociation of a tri-atomic system is designed and optimized. • ClCN molecule is chosen as tri-atomic system. • Optimization method is optimal control theory based simulated annealing technique. • Fourier grid Hamiltonian methodology is used for numerical calculations. • Polychromatic combined pulse is found to be most effective. In this communication, we design and optimize laser pulses to enhance the dissociation of a tri-atomic molecule using optimal control theory based adaptive simulated annealing technique. ClCN is chosen as tri-atomic molecular system as molecules containing fluorine and chlorine atoms are involved in the depletion of ozone layer and also dissociative electron attachment is possible. Fourier Grid Hamiltonian based 2D mean field methodology has been used for numerical calculations. We find an effective laser pulse by combining polychromatic Gaussian pulses and polychromatic linear pulses with different frequencies and different field intensities. [ABSTRACT FROM AUTHOR]

Photo dissociation dynamics of linear triatomic molecule, cyanogen chloride (ClCN) in polar medium have been explored using Fourier grid Hamiltonian (FGH) method based two-dimensional mean field methodology. Ground electronic state potential of the molecule is calibrated with coupled cluster singles and doubles (CCSD) level ab initio theory using Gaussian 03 package taking 6-311++G(3df,2pd) as the basis set and fitted with two-dimensional coupled Morse potential and this potential is used for numerical calculation. Time-integrated probability current density is used as the measure of dissociation probability. Monochromatic and bichromatic laser fields are used as the external field and dissociation probability is calculated as the function of field frequency, dipolar position and pulse shape. [ABSTRACT FROM AUTHOR]

Abstract: The ground state (v=0) millimeter-wave rotational spectrum of cyanogen chloride (ClCN) and some of its isotopic species have been investigated in the frequency region: 40.0–75.0GHz. ClCN was produced by DC discharge through a mixture of 3-chlorobenzonitrile and tri-chloroethylene. The millimeter-wave spectrometer used is a source-modulated system combined with a free space glass discharge cell. Millimeter-wave radiation has been produced using a frequency multiplier, the fundamental radiation source being klystrons. The quadrupole hyperfine structures of 35Cl and 37Cl have been resolved, measured and analyzed. Finally, internuclear distances of ClCN have been determined using the Kraitchman''s equation and compared with the previously reported values. Satisfactory agreements between the DFT-B3LYP/6-311++g(3d,3p) calculations and experimental values were found for internuclear distances and dipole moment. Based on the results of ab initio calculations at the MP4 level, ClCN was found to have a bent structure in the first excited electronic state. [Copyright &y& Elsevier]

The adsorption and decomposition of ClCN on Si (100)-(2×1) surface is studied by using density functional theory and the cluster model method. The Si9H12 dimer cluster is used to simulate the surface. The present calculations show that ClCN may be adsorbed molecularly without a barrier onto the surface with both linear (L1) and parallel (S1) modes. L1 can isomerize to S1 with a small barrier of 5.6 kcal/mol. Both ClCN and ClNC end-on adsorbates were found to dissociate readily to produce Cl and CN species, which was in excellent agreement with the experiment. [ABSTRACT FROM AUTHOR]