Akram Aadil Khan

The solid-state landscape of highly flexible organic molecules often presents profound challenges and opportunities in materials chemistry, critically dictating macroscopic, physicochemical, and biopharmaceutical properties. Herein, we report voxelotor, a BCS Class II drug historically developed for sickle cell disease, as a noteworthy model system to elucidate nucleation pathways and a non-classical structure-performance relationship, with bioavailability that is critically dependent on its solid form. We report the preferential crystallization, multigram scale-up, and comprehensive structural elucidation of seven distinct polymorphic forms (Forms I-VII), including four previously undiscovered solid phases. Single-crystal X-ray diffraction and computational lattice energy calculations, including Hirshfeld surface analysis, show that its rich polymorphic diversity is rooted in extreme torsional adaptability (variations in τ2 from -160.0° to +110.0°), which drives parallel displaced π···π stacking and hydrogen-bonded assemblies. Thermal and humidity stress profiling discloses a complex relationship between thermodynamic stability and kinetic trapping. Notably, we identified paradoxical stability behavior in which seemingly robust, high lattice energy metastable states (e.g., Forms III, IV, V, and VI) undergo temperature- and moisture-promoted structural transformation and solid-state conversion to Form I crystals, which exhibit greater stability under ambient conditions. Crucially, biopharmaceutical and pharmacokinetic evaluation showed a divergence between drug solubility and biological efficacy. The kinetically trapped Form VI exhibited the highest equilibrium aqueous solubility. Form II exhibited superior systemic exposure in rats and the highest ex vivo anti-sickling efficacy (74% inhibition at 200 μM). Collectively, these findings offer fundamental insight into how subtle solid-state energetic balance and specific molecular conformations can influence solubility behavior. By demonstrating how structural nuances dictate superior macroscopic performance, this study provides a robust, predictive framework for rationalizing solid-form selection in highly flexible functional drugs.

Phase engineering of 0D Sb halide hybrid regulates singlet–triplet exciton dynamics across crystalline, and amorphous phases. Amorphization induces exclusive fluorescence, revealing a disorder-mediated pathway for tunable emission.

Electrochemical nitrate reduction to ammonia offers a sustainable alternative to the Haber-Bosch process while mitigating nitrate pollution. However, the development of nitrate reduction reaction catalysts is hindered by ambiguous active-site structures, poorly understood structure–activity relationships, and limited mechanistic understanding. In this regard, herein we report a homologous series of atomically precise Ni-tiara clusters, [Ni4(L)8], [Ni5(L)10], and [Ni6(L)12] (L = cyclopentylmethanethiolate), which provide a structurally definable molecular platform for systematically decoding nuclearity effects in NO3RR. [Ni5(L)10] exhibits outstanding activity, delivering NH3 Faradaic efficiencies of 95.1% in homogeneous systems and 87.8% in heterogeneous systems at –1.5 V vs Fc+/Fc. Structural analysis by SC-XRD confirmed that the odd nuclearity of Ni5 introduces geometric strain through a nonalternating axial/equatorial thiolate arrangement, generating electronically differentiated Ni centres that promote mixed-valent Ni+/Ni0 intermediates and balanced reduction kinetics. Consequently, Ni5 exhibited balanced reactivity across the multistep reduction pathway with no single rate-limiting step dominating under the optimal operating potential. In contrast, NO2– → NH2OH and NO2– → *NO transformation for Ni4 and Ni6, respectively, were identified as the rate-limiting segment. These results establish a nuclearity-dependent structure–activity relationship and provide molecular-level design principles for efficient multinuclear Ni electrocatalysts for selective ammonia conversion.

Chemical design of metal halide hybrids (MHHs) with suppressed melting point (T_m) allows access to glassy phases from their liquid-melts. Thermal phase change (crystal-melt-glass) properties of glassy MHHs (with glass transition temperature T_g > room temperature) have been exploited for device applications. However, room temperature stable supercooled liquid (SCL) MHHs (with T_g < room temperature), originating from glass-SCL phase change, remain inaccessible. Here, a molecular design strategy is reported to access ambient stable, melt-processable, SCL multimetallic bromide hybrids (Mn²⁺,Cd²⁺; Mn²⁺,Zn²⁺; Benzyltributylammonium) with low T_g (15-16 °C), low T_m (90-100 °C), green luminescence, and high optical transparency. Structural, optical, thermal, and computational analyses highlight chemical design principles and support dopant (Mn²⁺) based luminescence. Rheological measurements confirm the SCL phase that shows thermal hysteresis and estimate relaxation time scales. This work provides a new material platform showcasing enhanced melt-processability for fabrication of moldable devices, unravelling chemical makeup-property correlation and expanding the material phase types of MHHs.

A robust Ag(I)-catalyzed tandem heterocyclization/[3 + 2] cycloaddition of α-alkynylenones with β-enaminones was developed, enabling efficient synthesis of cyclopenta[c]furans with good yields, operational simplicity, and broad substrate scope. In addition, it also presents an extended methodology to synthesize unsymmetrical tri(hetero)aryl methane having chromone and furan/pyrrole scaffolds by a slight modification of starting materials. Moreover, the synthesized cyclopenta[c]furans exhibit good fluorescence properties with quantum yields ranging from 0.33 to 0.53, as suggested by the photophysical studies.

Herein, we describe the formation of biologically relevant N-α,β-unsaturated acyl sulfoximines via phosphine-catalyzed C-C bond activation of cyclopropenones with weakly nucleophilic sulfoximines. The new process does not require a transition metal or external oxidant and displays high regioselectivity and exclusive E-selectivity. Other salient features of the method are a broad substrate scope, high compatibility with various functional groups, and high atom economy.

The crystal structure of poly[di-μ₂-nitrato-μ₂-urea-strontium(II)], [Sr(NO₃)₂(CH₄N₂O)] _n , was determined using single-crystal X-ray diffraction. Crystallizing in the orthorhombic space group Aba2, the asymmetric unit consists of an Sr^II cation, two nitrate anions, and two half urea molecules. The Sr^II cation adopts a distorted decahedral geometry coordinated by ten oxygen atoms, with Sr—O bond lengths ranging from 2.573 (3) to 2.847 (5) Å. The nitrate anions act as bidentate ligands, displaying both terminal and bridging coordination modes. The structure features a robust coordination network supported by hydrogen bonding. These results provide insight into the coordination behaviour of Sr^II with nitrate and urea ligands, contributing to the understanding of supramolecular architectures in metal–organic frameworks (MOFs).

The synthesis, crystal structure, and Hirshfeld surface analysis of N-(4-methoxyphenyl)picolinamide (MPPA), C₁₃H₁₂N₂O₂, are presented. MPPA crystallizes in the monoclinic space group P2₁/n, with a single molecule in the asymmetric unit. Structural analysis reveals that all non-hydrogen atoms are nearly coplanar, and the molecule exhibits two intramolecular hydrogen bonds that stabilize its conformation. Supramolecular features include significant intermolecular interactions, primarily C—H...π and various hydrogen bonds, contributing to the overall crystal cohesion, as confirmed by energy framework calculations yielding a total interaction energy of −138.3 kJ mol⁻¹. Hirshfeld surface analysis indicates that H...H interactions dominate, followed by C...H and O...H interactions, highlighting the role of van der Waals forces and hydrogen bonding in crystal packing.