Dipolar cycloaddition of ethyl isocyanoacetate to 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines: highly regio- and chemoselective synthesis of substituted imidazo[1,5-a]quinoxaline-3-carboxylates

An efficient route for regio- and chemoselective synthesis of substituted 3-(carboethoxy)imidazo[1,5-a]quinoxalines and novel diimidazo[1,5-a:5',1'-c]quinoxalines via base-induced cycloaddition of ethyl isocyanoacetate to unsymmetrically substituted 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines has been reported.     

Ferrocene derivatives supported on poly(N-vinylpyrrolidin-2-one) (PVP): Synthesis of new water-soluble electrochemically active probes for biomolecules

Carboxy-terminated polyvinylpyrrolidin-2-one (PVP) has been used as a new water-soluble and biocompatible polymeric support for a series of ferrocene labeled amino acid and peptide nucleic acid (PNA) monomer derivatives 4-7. The organometallic polymer-conjugates thus obtained are new and potentially useful as water-soluble electrochemically active probes for biomolecules. In view of such application, their electrochemical activity has been evaluated and has proved very high notwithstanding the complexity and bulkiness of the molecule, affording detection limits down to 10⁻⁸ M in the aqueous medium.     

Imaging in turbid media using quasi-ballistic photons

We study by means of experiments and Monte Carlo simulations, the scattering of light in random media, to determine the distance up to which photons travel along almost undeviated paths within a scattering medium, and are therefore capable of casting a shadow of an opaque inclusion embedded within the medium. Such photons are isolated by polarisation discrimination wherein the plane of linear polarisation of the input light is continuously rotated and the polarisation preserving component of the emerging light is extracted by means of a Fourier transform. This technique is a software implementation of lock-in detection. We find that images may be recovered to a depth far in excess of that predicted by the diffusion theory of photon propagation. To understand our experimental results, we perform Monte Carlo simulations to model the random walk behaviour of the multiply scattered photons. We present a new definition of a diffusing photon in terms of the memory of its initial direction of propagation, which we then quantify in terms of an angular correlation function. This redefinition yields the penetration depth of the polarisation preserving photons. Based on these results, we have formulated a model to understand shadow formation in a turbid medium, the predictions of which are in good agreement with our experimental results.     

Scale invariant amplitude modulated phase-only filtering

A new synthetic discriminant-function-based amplitude modulated phase-only filtering technique is proposed for scale invariant pattern recognition. This technique has been found to yield improved correlation output when compared with the alternate techniques. The proposed technique is inherently suitable for optical implementation using the currently available spatial light modulators. Simulation results confirm the effectiveness of the proposed technique.     

Rationalizing the generation of broad spectrum antibiotics with the addition of a positive charge

Antibiotic resistance of Gram-negative bacteria is largely attributed to the low permeability of their outer membrane (OM). Recently, we disclosed the eNTRy rules, a key lesson of which is that the introduction of a primary amine enhances OM permeation in certain contexts. To understand the molecular basis for this finding, we perform an extensive set of molecular dynamics (MD) simulations and free energy calculations comparing the permeation of aminated and amine-free antibiotic derivatives through the most abundant OM porin of E. coli, OmpF. To improve sampling of conformationally flexible drugs in MD simulations, we developed a novel, Monte Carlo and graph theory based algorithm to probe more efficiently the rotational and translational degrees of freedom visited during the permeation of the antibiotic molecule through OmpF. The resulting pathways were then used for free-energy calculations, revealing a lower barrier against the permeation of the aminated compound, substantiating its greater OM permeability. Further analysis revealed that the amine facilitates permeation by enabling the antibiotic to align its dipole to the luminal electric field of the porin and form favorable electrostatic interactions with specific, highly-conserved charged residues. The importance of these interactions in permeation was further validated with experimental mutagenesis and whole cell accumulation assays. Overall, this study provides insights on the importance of the primary amine for antibiotic permeation into Gram-negative pathogens that could help the design of future antibiotics. We also offer a new computational approach for calculating free-energy of processes where relevant molecular conformations cannot be efficiently captured.

A rapid pathway sampling method combining Monte Carlo and graph theory, developed to describe permeation pathways through outer membrane porins, can distinguish between structurally similar analogs with different permeabilities.     

Interventional Fairness with Indirect Knowledge of Unobserved Protected Attributes

The deployment of machine learning (ML) systems in applications with societal impact has motivated the study of fairness for marginalized groups. Often, the protected attribute is absent from the training dataset for legal reasons. However, datasets still contain proxy attributes that capture protected information and can inject unfairness in the ML model. Some deployed systems allow auditors, decision makers, or affected users to report issues or seek recourse by flagging individual samples. In this work, we examine such systems and consider a feedback-based framework where the protected attribute is unavailable and the flagged samples are indirect knowledge. The reported samples are used as guidance to identify the proxy attributes that are causally dependent on the (unknown) protected attribute. We work under the causal interventional fairness paradigm. Without requiring the underlying structural causal model a priori, we propose an approach that performs conditional independence tests on observed data to identify such proxy attributes. We theoretically prove the optimality of our algorithm, bound its complexity, and complement it with an empirical evaluation demonstrating its efficacy on various real-world and synthetic datasets.     

Three bis‐ortho‐diynyl­arenes (BODA)

The molecule of 3,3′,4,4′‐tetrakis­(phenyl­ethynyl)­bi­phenyl, C₄₄H₂₆, is approximately planar and is located on a crystallographic inversion center. Bis­[3,4‐bis­(phenyl­ethynyl)­phenyl] ether, C₄₄H₂₆O, has mol­ecules located on twofold symmetry axes, whereas the molecule of 2,2‐bis­[3,4‐bis­(phenyl­ethynyl)­phenyl]­propane, C₄₇H₃₂, does not exhibit any molecular symmetry.     

Attaining record-high magnetic exchange,magnetic anisotropy and blocking barriers in dilanthanofullerenes

While the blocking barrier (U_eff) and blocking temperature (T_B) for “Dysprocenium” SIMs have been increased beyond liquid N₂ temperature, device fabrication of these molecules remains a challenge as low-coordinate Ln³⁺ complexes are very unstable. Encapsulating the lanthanide ion inside a cage such as a fullerene (called endohedral metallofullerene or EMF) opens up a new avenue leading to several Ln@EMF SMMs. The ab initio CASSCF calculations play a pivotal role in identifying target metal ions and suitable cages in this area. Encouraged by our earlier prediction on Ln₂@C₇₉N, which was verified by experiments, here we have undertaken a search to enhance the exchange coupling in this class of molecules beyond the highest reported value. Using DFT and ab initio calculations, we have studied a series of Gd₂@C_2n (30 ≤ 2n ≤ 80), where an antiferromagnetic J_Gd⋯Gd of −43 cm⁻¹ was found for a stable Gd₂@C₃₈-D_3h cage. This extremely large and exceptionally rare 4f⋯4f interaction results from a direct overlap of 4f orbitals due to the confinement effect. In larger cages such as Gd₂@C₆₀ and Gd₂@C₈₀, the formation of two centre-one-electron (2c-1e⁻) Gd–Gd bonds is perceived. This results in a radical formation in the fullerene cage leading to its instability. To avoid this, we have studied heterofullerenes where one of the carbon atoms is replaced by a nitrogen atom. Specifically, we have studied Ln₂@C₅₉N and Ln₂@C₇₉N, where strong delocalisation of the electron yields a mixed valence-like behaviour. This suggests a double-exchange (B) is operational, and CASSCF calculations yield a B value of 434.8 cm⁻¹ and resultant J_Gd–rad of 869.5 cm⁻¹ for the Gd₂@C₅₉N complex. These parameters are found to be two times larger than the world-record J reported for Gd₂@C₇₉N. Further ab initio calculations reveal an unprecedented U_cal of 1183 and 1501 cm⁻¹ for Dy₂@C₅₉N and Tb₂@C₅₉N, respectively. Thus, this study offers strong exchange coupling as criteria for new generation SMMs as the existing idea of enhancing the blocking barrier via crystal field modulation has reached its saturation point.

Using ab initio calculations, we have made some robust predictions towards lanthanofullerene SMMs exhibiting remarkable characteristics.     

A family of ferro- and antiferromagnetically coupled decametallic chromium(III) wheels

The synthesis and crystal structures of a family of decametallic Cr(III) "molecular wheels" are reported, namely [Cr10(OR)20(O2CR')10] [R' = Me, R = Me (1), Et (2); R' = Et, R = Me (3), Et (4); R' = CMe3, R = Me (5), Et (6)]. Magnetic studies on 1-6 reveal a remarkable dependence of the magnetic behaviour on the nature of R. In each pair of complexes with a common carboxylate (R') the nearest neighbour CrCr magnetic exchange coupling is more antiferromagnetic for the ethoxide-bridged (R = Et) cluster than for the methoxide analogue. In complexes 2, 4 and 6 the overall coupling is weakly antiferromagnetic resulting in diamagnetic (S = 0) ground states for the cluster, whilst in 1 and 5 it is weakly ferromagnetic thus resulting in very high-spin ground states. This ground state has been probed directly in the perdeuterated version of 1 ([D]1) by inelastic neutron scattering experiments, and these support the S = 15 ground state expected for ferromagnetic coupling of ten Cr(III) ions, and they also indicate that a single J-value model is inadequate. The ground state of 5 is large but not well defined. The trends in J on changing R are further supported by density functional calculations on 1-6, which are in excellent agreement with experiment. The very large changes in the nature of the ground state between 1 and 2, and 5 and 6 are the result of relatively small changes in J that happen to cross J = 0, hence changing the sign of J.