Unravelling the metabolomic diversity of pigmented and non-pigmented traditional rice from Tamil Nadu, India.

Rice metabolomics is widely used for biomarker research in the fields of pharmacology. As a consequence, characterization of the variations of the pigmented and non-pigmented traditional rice varieties of Tamil Nadu is crucial. These varieties possess fatty acids, sugars, terpenoids, plant sterols, phenols, carotenoids and other compounds that plays a major role in achieving sustainable development goal 2 (SDG 2). Gas-chromatography coupled with mass spectrometry was used to profile complete untargeted metabolomics of Kullkar (red colour) and Milagu Samba (white colour) for the first time and a total of 168 metabolites were identified. The metabolite profiles were subjected to data mining processes, including principal component analysis (PCA), Orthogonal Partial Least Square Discrimination Analysis (OPLS-DA) and Heat map analysis. OPLS-DA identified 144 differential metabolites between the 2 rice groups, variable importance in projection (VIP) ≥ 1 and fold change (FC) ≥ 2 or FC ≤ 0.5. Volcano plot (64 down regulated, 80 up regulated) was used to illustrate the differential metabolites. OPLS-DA predictive model showed good fit (R2X = 0.687) and predictability (Q2 = 0.977). The pathway enrichment analysis revealed the presence of three distinct pathways that were enriched. These findings serve as a foundation for further investigation into the function and nutritional significance of both pigmented and non-pigmented rice grains thereby can achieve the SDG 2.

Design of Isoindigo-Based Small-Molecule Donors for Bulk Heterojunction Organic Solar Cell Applications in Combination with Nonfullerene Acceptors.

The development of small-molecule organic solar cells with the required efficiency depends on the information obtained from molecular-level studies. In this context, 39 small-molecule donors featuring isoindigo as an acceptor moiety have been meticulously crafted for potential applications in bulk heterojunction organic solar cells. These molecules follow the D2-A-D1-A-D2 and D2-A-π-D1-π-A-D2 framework. Similar molecules considered in the previous experimental study (molecules R1 ((3E,3″E)-6,6″-(benzo[1,2-b:4,5-b']dithiophene-2,6-diyl)bis(1,1'-dimethyl-[3,3'-biindolinylidene]-2,2'-dione)) and R2 ((3E,3″E)-6,6″-(4,8-dimethoxybenzo[1,2-b:4,5-b']dithiophene-2,6-diyl)bis(1,1'-dimethyl-[3,3'-biindolinylidene]-2,2'-dione))) have been chosen as reference molecules. Molecules with and without π-spacers have been considered to understand the impact of the length of the π-spacer on intramolecular charge-transfer transitions and absorption properties. A detailed investigation is carried out to establish the relationship between the structure and photovoltaic parameters using density functional theory and time-dependent density functional theory methods. The newly developed molecules exhibit better electronic, excited-state, and charge transport properties than the reference molecules. Additionally, model donor-acceptor interfaces are constructed by integrating the designed donor molecules with fullerene/nonfullerene acceptors. The electronic and excited-state properties of these interfaces are rigorously evaluated. Results elucidate that the donor comprising of isoindigo-bithiophene-pyrroloindacenodithiophene (IIG-T2-PIDT) emerges as a promising candidate for bulk heterojunction solar cells based on nonfullerene acceptors. This research provides systematic design strategies for the development of small-molecule donors for organic solar cells.

Harnessing halogen bond donors for enhanced nitrogen reduction: a case study on metal-free boron nitride single-atom catalysts.

Developing efficient catalysts for ammonia synthesis is increasingly crucial but remains a formidable challenge due to the lack of robust design criteria, particularly in addressing the activity and selectivity issues, especially in electrochemical nitrogen reduction reactions (NRR). In this study, we systematically investigated the catalytic potential of hexagonal boron nitride (BN) embedded with non-metal (C, Si, P and S) atoms as an electrocatalyst for the nitrogen reduction reaction using density functional theory (DFT) computations. The preference for non-metal-doped BN nanomaterials stems from their ability to suppress hydrogen evolution and their environmentally friendly nature, in contrast to transition metals. Among the designed single-atom catalysts (SACs), Si-doped boron nitride (SiBBN) exhibits a favorable inclination toward activating nitrogen, which is determined by the combination of advantageous molecular orbital coupling and formation of a covalent bond with the N2 molecule. Under thermal conditions, the first protonation step emerges as the rate-determining step (22.66 kcal mol-1) for SiBBN. Conversely, under electrochemical conditions, the final elementary step becomes the potential-determining step (PDS) with 2.38 eV. We explored the impact of the exogenous addition of Lewis acids (alkali metal ions, neutral boron Lewis acids, and halogen bond donors) on modulating the electrochemical NRR activity. Our results highlight the pivotal role of halogen bond donors as catalytic promoters in facilitating electron density transfer through activated N2, establishing a push-pull charge transfer mechanism that populates the distal nitrogen more than the proximal nitrogen. This facilitates the potential requirements for the first reduction step. The synergistic effect of both halogen bonding and hydrogen bonding interactions in the final reduction step was proven to be the main determinant for a significant reduction in the PDS from 2.38 to 0.10 V. Notably, this study unveils the pioneering role of halogen bond donors as promoters for NRR, providing valuable insights into the development of robust metal-free catalysts and promoters in experimental research.

Organocatalyzed Enantio- and Diastereoselective Formal Domino 1,3-Dipolar Cycloaddition/Rearrangement: Synthesis of Chiral Pyrrolo-thiazine-2-carbaldehydes.

An efficient approach for the synthesis of chiral pyrrolo[1,2-d][1,4]thiazine-2-carbaldehydes is achieved via formal 1,3-dipolar cycloaddition/rearrangement reactions of benzothiazolium salt and α,ß-unsaturated aldehydes, utilizing an asymmetric organocatalyst. This process results in the formation of fluorescent, highly enantioenriched chiral molecules with three contiguous stereogenic centers, one of which is a chiral quaternary center, with excellent yields and enantio- and diastereoselectivity. A computational study demonstrated the understanding of the reaction mechanism. The synthetic utility of this protocol was successfully employed for gram scale synthesis. Fluorescent and in silico studies showed the application of the present methodology.

A Novel Quasi-Planar Two-dimensional Carbon Sulfide with Negative Poisson's Ratio and Dirac Fermions.

In the present study, a novel and unconventional two-dimensional (2D) material with Dirac electronic features has been designed using sulflower with the help of density functional theory methods and first principles calculations. This 2D material comprises of hetero atoms (C, S) and belongs to the tetragonal lattice with P4 /nmm space group. Scrutiny of the results show that the 2D nanosheet exhibits a nanoporous wave-like geometrical structure. Quantum molecular dynamics simulations and phonon mode analysis emphasize the dynamical and thermal stability. The novel 2D nanosheet is an auxetic material with an anisotropy in the in-plane mechanical properties. Both composition and geometrical features are completely different from the conditions necessary for the formation of Dirac cones in graphene. However, the presence of semi-metallic nature, linear band dispersion relation, massive fermions and massless Dirac fermions are observed in the novel 2D nanosheet. The massless Dirac fermions exhibit highly isotropic Fermi velocities (vf =0.68×106  m/s) along all crystallographic directions. The zero-band gap semi metallic features of the novel 2D nanosheet are perturbative to the electric field and external strain.

Acetylene-Mediated Borophosphene Dirac Materials as Efficient Anode Materials for Lithium-Ion Batteries.

Generally, graphynes have been generated by the insertion of acetylenic content (-C≡C-) in the graphene network in different ratios. Also, several aesthetically pleasing architectures of two-dimensional (2D) flatlands have been reported with the incorporation of acetylenic linkers between the heteroatomic constituents. Prompted by the experimental realization of boron phosphide, which has provided new insights on the boron-pnictogen family, we have modelled novel forms of acetylene-mediated borophosphene nanosheets by joining the orthorhombic borophosphene stripes with different widths and with different atomic constituents using acetylenic linkers. Structural stabilities and properties of these novel forms have been assessed using first-principles calculations. Investigation of electronic band structure elucidates that all the novel forms show the linear band crossing closer to the Fermi level at Dirac point with distorted Dirac cones. The linearity in the hole and electronic bands impose the high Fermi velocity to the charge carriers close to that of graphene. Finally, we have also unravelled the propitious features of acetylene-mediated borophosphene nanosheets as anodes in Li-ion batteries.

Defect Engineered Ternary Spinel: An Efficient Cathode for an Aqueous Rechargeable Zinc-Ion Battery of Long-Term Cyclability.

The rational defect engineering of Mn-based spinel cathode materials by metal-ion doping and vacancy creation fosters reversible intercalation/deintercalation of charge carriers and boosts the charge storage performance of an aqueous rechargeable zinc-ion battery (ZIB). Herein, we demonstrate the Zn2+ ion storage performance of a defect-engineered ternary spinel cathode based on Zn, Ni, and Mn. The defect engineering of ZnMn2O4 is achieved by Ni2+ doping and creating a cation (Mn3+ and Zn2+) deficiency. The engineered cathode material has cubic spinel structure in contrast to the defect-free ZnMn2O4. The DFT studies show that the defect engineering modifies the electronic structure and improves the electronic conductivity. An aqueous rechargeable ZIB is fabricated by using the spinel cathode, and its performance is evaluated in terms of charge-discharge cycling stability, specific capacity, and so on. The ternary spinel-based ZIB has a very long charge-discharge cycling stability with a specific capacity as high as 265 mAh g-1 (at 100 mA g-1). A 2-fold enhancement in the specific capacity is observed after 5000 cycles. Ni doping affords ultralong cycling stability. The self-discharge studies for a year show that the device retains 63% of the initial performance.

Applying polypharmacology approach for drug repurposing for SARS-CoV2.

Exploring the new therapeutic indications of known drugs for treating COVID-19, popularly known as drug repurposing, is emerging as a pragmatic approach especially owing to the mounting pressure to control the pandemic. Targeting multiple targets with a single drug by employing drug repurposing known as the polypharmacology approach may be an optimised strategy for the development of effective therapeutics. In this study, virtual screening has been carried out on seven popular SARS-CoV-2 targets (3CLpro, PLpro, RdRp (NSP12), NSP13, NSP14, NSP15, and NSP16). A total of 4015 approved drugs were screened against these targets. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected based on the docking score, ability to interact with four or more targets and having a reasonably good number of interactions with key residues in the targets. The MD simulations and MM-PBSA studies showed reasonable stability of protein-drug complexes and sustainability of key interactions between the drugs with their respective targets throughout the course of MD simulations. The identified four drug molecules were also compared with the known drugs namely elbasvir and nafamostat. While the study has provided a detailed account of the chosen protein-drug complexes, it has explored the nature of seven important targets of SARS-CoV-2 by evaluating the protein-drug complexation process in great detail. Graphical abstract: Drug repurposing strategy against SARS-CoV2 drug targets. Computational analysis was performed to identify repurposable approved drug candidates against SARS-CoV2 using approaches such as virtual screening, molecular dynamics simulation and MM-PBSA calculations. Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected as potential candidates. Supplementary Information: The online version contains supplementary material available at 10.1007/s12039-022-02046-0.

Cascade aryne insertion/vinylogous aldol reaction of vinyl-substituted ß-keto/enol carbonyls.

Cyclic and acyclic vinyl substituted ß-keto/enol carbonyl substrates, on reaction with arynes, result in differentially substituted naphthyl carbocycles, hitherto difficult to synthesize with existing protocols. While the substitutions on the arynes have no role, the ring size of the cyclic ß-keto/enol esters has a profound influence on the product formation.

Diastereoselective access to [4,4]-carbospirocycles: governance of thermodynamic enolates with an organocatalyst in vinylogous cascade annulation.

A vinylogy concept driven annulation strategy is developed to access [4,4]-carbospirocycles from alkylidene malononitriles and cyclopentene-1,3-diones. The reaction is catalyzed by an inexpensive organocatalyst and products with three stereocenters were obtained as a single diastereomer in high yields. The spiro-selectivity originates from the reaction of the thermodynamic enolate intermediate which is fundamentally intriguing.

Unorthodox cascade reaction of arynes and N-nitrosamides leading to indazole scaffolds.

An unusual cascade annulation of arynes with N-alkyl-N-nitrosamides is developed by leveraging aryne σ-insertion and C(sp3)-H bond functionalization strategies under transition-metal-free conditions at ambient temperature, offering functionalized indazoles in high yields and regioselectivity. The protocol is scalable and exhibits a broad substrate scope. The reaction mechanism is also studied with DFT calculations.

A study on structural characterization of potential impurities of Sugammadex sodium using LC/ESI/QTOF/MS/MS and NMR.

The first selective relaxant binding agent (SRBA), Sugammadex sodium (SGS) is used to reverse anesthesia. A study of the process related and degradation products will help to optimize process parameters and also to develop the analytical methods and set the quality standard for a quality control strategy in pharmaceutical industry. During the manufacture of SGS, all the process related impurities are controlled in every stage and process related and degradation products are controlled in the active pharmaceutical ingredient (API) as per ICH guidelines. A total of nine process related and degradation impurities of SGS (Impurity-A to Impurity-I) were isolated and characterized by using LC/ESI/QTOF/MS/MS and NMR studies.

Assessment of Amyloid Forming Tendency of Peptide Sequences from Amyloid Beta and Tau Proteins Using Force-Field, Semi-Empirical, and Density Functional Theory Calculations.

A wide variety of neurodegenerative diseases are characterized by the accumulation of protein aggregates in intraneuronal or extraneuronal brain regions. In Alzheimer's disease (AD), the extracellular aggregates originate from amyloid-ß proteins, while the intracellular aggregates are formed from microtubule-binding tau proteins. The amyloid forming peptide sequences in the amyloid-ß peptides and tau proteins are responsible for aggregate formation. Experimental studies have until the date reported many of such amyloid forming peptide sequences in different proteins, however, there is still limited molecular level understanding about their tendency to form aggregates. In this study, we employed umbrella sampling simulations and subsequent electronic structure theory calculations in order to estimate the energy profiles for interconversion of the helix to ß-sheet like secondary structures of sequences from amyloid-ß protein (KLVFFA) and tau protein (QVEVKSEKLD and VQIVYKPVD). The study also included a poly-alanine sequence as a reference system. The calculated force-field based free energy profiles predicted a flat minimum for monomers of sequences from amyloid and tau proteins corresponding to an α-helix like secondary structure. For the parallel and anti-parallel dimer of KLVFFA, double well potentials were obtained with the minima corresponding to α-helix and ß-sheet like secondary structures. A similar double well-like potential has been found for dimeric forms for the sequences from tau fibril. Complementary semi-empirical and density functional theory calculations displayed similar trends, validating the force-field based free energy profiles obtained for these systems.

Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: potential for repurposing in COVID-19-like conditions.

BACKGROUND: COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. METHODS: In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naïve mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication. RESULTS: Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-ß1 (TGF-ß1), IL-6, HIF-1α and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-ß1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2. CONCLUSION: Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.

Adhatoda vasica rescues the hypoxia-dependent severe asthma symptoms and mitochondrial dysfunction.

Severe asthma is a chronic airway disease that exhibits poor response to conventional asthma therapies. Growing evidence suggests that elevated hypoxia increases the severity of asthmatic inflammation among patients and in model systems. In this study, we elucidate the therapeutic effects and mechanistic basis of Adhatoda vasica (AV) aqueous extract on mouse models of acute allergic as well as severe asthma subtypes at physiological, histopathological, and molecular levels. Oral administration of AV extract attenuates the increased airway resistance and inflammation in acute allergic asthmatic mice and alleviates the molecular signatures of steroid (dexamethasone) resistance like IL-17A, KC (murine IL-8 homologue), and HIF-1α (hypoxia-inducible factor-1α) in severe asthmatic mice. AV inhibits HIF-1α levels through restoration of expression of its negative regulator-PHD2 (prolyl hydroxylase domain-2). Alleviation of hypoxic response mediated by AV is further confirmed in the acute and severe asthma model. AV reverses cellular hypoxia-induced mitochondrial dysfunction in human bronchial epithelial cells-evident from bioenergetic profiles and morphological analysis of mitochondria. In silico docking of AV constituents reveal higher negative binding affinity for C and O-glycosides for HIF-1α, IL-6, Janus kinase 1/3, TNF-α, and TGF-ß-key players of hypoxia inflammation. This study for the first time provides a molecular basis of action and effect of AV whole extract that is widely used in Ayurveda practice for diverse respiratory ailments. Further, through its effect on hypoxia-induced mitochondrial dysfunction, the study highlights its potential to treat severe steroid-resistant asthma.

Nitrogen Fixation at the Edges of Boron Nitride Nanomaterials: Synergy of Doping.

Synthesis of ammonia at ambient conditions is very demanding yet challenging to achieve due to the production of ammonia fuel, which is considered to be a future fuel for sustainable energy. In this context, computational studies on the catalytic activity of the edge sites of boron nitride nanomaterials for possible nitrogen reduction into ammonia have been investigated. Geometrical and electronic properties of zigzag and armchair B-open edges of BN sheet (BOE) models have been unraveled to substantiate their catalytic nature. Results reveal that BOE sites exhibit very high potential determining steps (PDS) of 2.0 eV. Doping of carbon (C) at the nitrogen center, which is vicinal to the BOE site reduces the PDS of the N2 reduction reaction (NRR) (to 1.18-1.33 eV) due to the regulation of charge distribution around the active BOE site. Further, the NRR at the C doped at various edge sites of a boron nitride sheet (BNS) has also been studied in detail. Among the 12 new C-doped defective BNS models, 9 model catalysts are useful for nitrogen activation through either chemisorption or physisorption. Among these, ZC N , AC N , and ZC BV models are efficient in catalyzing NRR with lower PDS of 0.86, 0.88, and 0.86 eV, respectively. The effect of carbon doping in tuning the potential requirements of NRR has been analyzed by comparing the relative stability of intermediates on the catalyst with and without carbon doping. Results reveal that C-doping destabilizes the intermediates compared to non-doped systems, thereby reducing the possibility of catalyst poisoning. However, their interactions with catalysts are good enough so that the NRR activity of the catalyst does not decrease due to C-doping.

Performance of Force-Field- and Machine Learning-Based Scoring Functions in Ranking MAO-B Protein-Inhibitor Complexes in Relevance to Developing Parkinson's Therapeutics.

Monoamine oxidase B (MAOB) is expressed in the mitochondrial membrane and has a key role in degrading various neurologically active amines such as benzylamine, phenethylamine and dopamine with the help of Flavin adenine dinucleotide (FAD) cofactor. The Parkinson's disease associated symptoms can be treated using inhibitors of MAO-B as the dopamine degradation can be reduced. Currently, many inhibitors are available having micromolar to nanomolar binding affinities. However, still there is demand for compounds with superior binding affinity and binding specificity with favorable pharmacokinetic properties for treating Parkinson's disease and computational screening methods can be majorly recruited for this. However, the accuracy of currently available force-field methods for ranking the inhibitors or lead drug-like compounds should be improved and novel methods for screening compounds need to be developed. We studied the performance of various force-field-based methods and data driven approaches in ranking about 3753 compounds having activity against the MAO-B target. The binding affinities computed using autodock and autodock-vina are shown to be non-reliable. The force-field-based MM-GBSA also under-performs. However, certain machine learning approaches, in particular KNN, are found to be superior, and we propose KNN as the most reliable approach for ranking the complexes to reasonable accuracy. Furthermore, all the employed machine learning approaches are also computationally less demanding.

Electrocatalytic Reduction of CO2 to Ethylene by Molecular Cu-Complex Immobilized on Graphitized Mesoporous Carbon.

The electrochemical reduction of carbon dioxide (CO2 ) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO2 to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO2 to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO2 in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions.

Scaffold-based Screening and Molecular Dynamics Simulation Study to Identify Two Structurally Related Phenolic Compounds as Potent MMP1 Inhibitors.

BACKGROUND: Matrix metalloproteinase 1 are zinc-dependent endopeptidases responsible for the controlled breakdown of the extracellular matrix resulting in the maintenance of homeostasis. Dysregulation of MMP1 leads to the progression of various pathological conditions like cancer, rheumatoid arthritis, cardiovascular disease, skin damage and fibrotic disorder. Thus, MMP1 inhibition is the potential drug target of many synthetic MMP1 inhibitors but lack of substrate specificity hinders their clinical applicability. Hence, inhibitors from natural products have gained widespread attention. OBJECTIVE: The present study attempts screening of novel MMP1 inhibitors from the ZINC database based on experimentally reported natural inhibitors of MMP1 as a scaffold. METHODS: Molecular docking study was performed with 19 experimentally reported natural inhibitors spanning across nine different classes followed by virtual screening using the selected compounds. The selected compounds were subjected to molecular dynamics simulation. RESULTS: Twenty compounds were screened with a cut-off of -9.0 kcal/mol of predicted free energy of binding, which further converged to 6 hits after docking studies. After comparing the docking result of 6 screened hits, two best compounds were selected. ZINC02436922 had the best interaction with six hydrogen bond formation to a relatively confined region in the S1'site of MMP1 and -10.01 kcal/mol of predicted free energy of binding. ZINC03075557 was the secondbest compound with -9.57 kcal/mol predicted binding free energy. Molecular dynamics simulation of ZINC02436922 and ZINC03075557 corroborates docking study. CONCLUSION: This study indicated phenolic compounds ZINC02436922 and ZINC03075557 as potential MMP1 inhibitors.

Aromaticity-Photovoltaic Property Relationship of Triphenylamine-Based D-π-A Dyes: Leads from DFT Calculations.

D-π-A-based dyes find a wide range of applications in molecular electronics and photovoltaics in general and dye-sensitized solar cells (DSSC) in particular. We speculated whether there exists a relationship between the degree of aromaticity of the π-spacers used in the D-π-A type dyes and their structural, electronic, energetic, photophysical, and intramolecular charge transfer properties. Triphenylamine (TPA) and cyanoacrylic acid (CAA) have been chosen as the donor and acceptor, respectively. In order to carry out the investigation systematically the π-spacers have been logically chosen based on their experimental resonance energies, which follows the order, furan < pyrrole < thiophene < pyridine < benzene. All the properties have been discussed based on the degree of aromaticity of the π-spacers. Geometric properties such as dihedral angles and bond lengths have been discussed extensively. Energy levels of the frontier molecular orbitals, electrochemical properties, namely, ground and excited state oxidation potentials (GSOP/ESOP), and change in Gibbs free energy for electron injection and regeneration (ΔGinj/ΔGreg) have also been evaluated. Photophysical properties like wavelength of maximum absorption (λmax), oscillator strength (f), light harvesting efficiency (LHE), and intramolecular charge transfer properties, viz., charge transfer distance (DCT), fraction of charge transferred (qCT), and change in dipole moment (µCT) have been assessed. The adsorption characteristics of dye with (TiO2)9 nanocluster have been studied along with their optical properties. Results reveal that the nature of the relationship between the aforementioned properties and the extent of aromaticity of the π-spacers is inherently multifaceted. It thus turns out that it is highly difficult to quantify the relationship. These properties of D-π1-π2-A molecules can be regarded to be arising from two groups, namely, π-spacers with lower and higher resonance energies. This results in a natural trade-off in selection of competing properties. The qualitative aromaticity photovoltaic property relationship thus obtained may serve as a guide to tailor-design various properties of D-π-A type dyes for application in the intramolecular charge transfer devices.