| 1. |
- Srivastava, Karnica, et al.
(author)
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Vibrational analysis and chemical activity of paracetamol-oxalic acid cocrystal based on monomer and dimer calculations : DFT and AIM approach
- 2016
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In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:12, s. 10024-10037
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Journal article (peer-reviewed)abstract
- The study of structural and spectral characteristics of a paracetamol-oxalic acid (PRA-OXA) cocrystal has been carried out using two models (monomer and dimer), with the aim to understand the supramolecular structure and intramolecular interactions within the cocrystal. The cocrystal has been characterized by infrared and Raman spectroscopy combined with quantum chemical calculations molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptors were used to understand the role of interactions involved in affecting the chemical reactivity of individual molecules in the cocrystal. It is observed that the C=O, N-H and O-H groups of paracetamol are involved in hydrogen bonds to form cocrystals. NBO analysis suggests that the two types of interactions LP(1)(N8) -> pi*(C9-O10) and LP(2)(O10) -> sigma*(O25-H28) are responsible for the stability of the molecule. AIM analysis suggested that the non-covalent interactions are moderate in nature. The calculated HOMO-LUMO energies reveal that the charge transfer occurs within the cocrystal. Chemical reactivity parameters show that the cocrystal is more active than paracetamol.
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| 2. |
- Verma, Priya, et al.
(author)
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Molecular Structure, Spectral Investigations, Hydrogen Bonding Interactions and Reactivity-Property Relationship of Caffeine-Citric Acid Cocrystal by Experimental and DFT Approach
- 2021
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In: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9
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Journal article (peer-reviewed)abstract
- The pharmaceutical cocrystal of caffeine-citric acid (CAF-CA, Form II) has been studied to explore the presence of hydrogen bonding interactions and structure-reactivity-property relationship between the two constituents CAF and Citric acid. The cocrystal was prepared by slurry crystallization. Powder X-ray diffraction (PXRD) analysis was done to characterize CAF-CA cocrystal. Also, differential scanning calorimetry (DSC) confirmed the existence of CAF-CA cocrystal. The vibrational spectroscopic (FT-IR and FT-Raman) signatures and quantum chemical approach have been used as a strategy to get insights into structural and spectral features of CAF-CA cocrystal. There was a good correlation among the experimental and theoretical results of dimer of cocrystal, as this model is capable of covering all nearest possible interactions present in the crystal structure of cocrystal. The spectroscopic results confirmed that (O33-H34) mode forms an intramolecular (C25 = O28∙∙∙H34-O33), while (O26-H27) (O39-H40) and (O43-H44) groups form intermolecular hydrogen bonding (O26-H27∙∙∙N24-C22, O39-H40∙∙∙O52 = C51 and O43-H44∙∙∙O86 = C83) in cocrystal due to red shifting and increment in bond length. The quantum theory of atoms in molecules (QTAIM) analysis revealed (O88-H89∙∙∙O41) as strongest intermolecular hydrogen bonding interaction with interaction energy −12.4247 kcal mol−1 in CAF-CA cocrystal. The natural bond orbital analysis of the second-order theory of the Fock matrix highlighted the presence of strong interactions (N∙∙∙H and O∙∙∙H) in cocrystal. The HOMO-LUMO energy gap value shows that the CAF-CA cocrystal is more reactive, less stable and softer than CAF active pharmaceutical ingredients. The electrophilic and nucleophilic reactivities of atomic sites involved in intermolecular hydrogen bond interactions in cocrystal have been demonstrated by mapping electron density isosurfaces over electrostatic potential i.e. plotting molecular electrostatic potential (MESP) map. The molar refractivity value of cocrystal lies within the set range by Lipinski and hence it may be used as orally active form. The results show that the physicochemical properties of CAF-CA cocrystal are enhanced in comparison to CAF (API).
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| 3. |
- Pandey, Jaya, et al.
(author)
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Studies of molecular structure, hydrogen bonding and chemical activity of a nitrofurantoin-L-proline cocrystal : a combined spectroscopic and quantum chemical approach
- 2016
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In: RSC Advances. - 2046-2069. ; 6:78, s. 74135-74154
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Journal article (peer-reviewed)abstract
- Nitrofurantoin (NTF) has been used as an antibacterial drug to treat bacterial infections of the urinary tract. The purpose of this work is to predict the hydrogen bonds (potential synthons) present in the cocrystal of nitrofurantoin-L-proline (NTF-LP) through a computational approach (DFT calculations) and validate using vibrational spectroscopic studies. The present study illustrates the formation and characterization of the cocrystal of NTF-LP. The molecular structure of the NTF-LP cocrystal has been predicted by forming several models on the basis of the hydrogen bonding patterns observed in other NTF cocrystals. A conformational study and potential energy surface scan have been plotted around three flexible bonds of the cocrystal molecule and two stable conformers have been obtained. NBO analysis of the second order perturbation theory of the Fock matrix suggests that interaction n1O(39) → σ*(N13–H21) is responsible for the stabilization of the molecule. Quantum theory of atoms in molecules (QTAIM) explains that all interactions are medium and partially covalent in nature as ∇2ρBCP > 0, HBCP < 0. The molecular electrostatic potential surface (MEPS) of the cocrystal has been visualized for its most electropositive potential in the region of the NH2+ group and most electronegative potential in the vicinity of the COO− group. The HOMO and LUMO energies and electronic charge transfer (ECT) confirms that charge flows from the co-former (LP) to NTF (API). Local reactivity descriptor parameters have been used to predict the reactive sites of the cocrystal and global reactivity descriptor parameters suggest that the cocrystal is softer thus more reactive in comparison to NTF. The experimental and theoretical results support the formation of the cocrystal through the strong hydrogen bond present between the NH group of NTF and carboxylate COO− group of LP and shows that LP is present in the zwitterionic form.
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| 4. |
- Prajapati, Preeti, et al.
(author)
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Combined spectroscopic and quantum chemical studies of ezetimibe
- 2016
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In: Journal of Molecular Structure. - : Elsevier BV. - 0022-2860 .- 1872-8014. ; 1125, s. 193-203
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Journal article (peer-reviewed)abstract
- Ezetimibe (EZT) is a hypocholesterolemic agent used for the treatment of elevated blood cholesterol levels as it lowers the blood cholesterol by blocking the absorption of cholesterol in intestine. Study aims to combine experimental and computational methods to provide insights into the structural and vibrational spectroscopic properties of EZT which is important for explaining drug substance physical and biological properties. Computational study on molecular properties of ezetimibe is presented using density functional theory (DFT) with B3LYP functional and 6-311++G(d,p) basis set. A detailed vibrational assignment has been done for the observed IR and Raman spectra of EZT. In addition to the conformational study, hydrogen bonding and molecular docking studies have been also performed. For conformational studies, the double well potential energy curves have been plotted for the rotation around the six flexible bonds of the molecule. UV absorption spectrum was examined in methanol solvent and compared with calculated one in solvent environment (IEF-PCM) using TD-DFT/6-31G basis set. HOMO-LUMO energy gap of both the conformers have also been calculated in order to predict its chemical reactivity and stability. The stability of the molecule was also examined by means of natural bond analysis (NBO) analysis. To account for the chemical reactivity and site selectivity of the molecules, molecular electrostatic potential (MEPS) map has been plotted. The combination of experimental and calculated results provide an insight into the structural and vibrational spectroscopic properties of EZT. In order to give an insight for the biological activity of EZT, molecular docking of EZT with protein NPC1L1 has been done.
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| 5. |
- Solé Navais, Pol, et al.
(author)
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Genetic effects on the timing of parturition and links to fetal birth weight.
- 2023
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In: Nature genetics. - 1546-1718. ; 55:4, s. 559-567
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Journal article (peer-reviewed)abstract
- The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n=195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n=136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
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| 6. |
- Verma, Priya, et al.
(author)
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Experimental and Quantum Chemical Studies of Nicotinamide-Oxalic Acid Salt: Hydrogen Bonding, AIM and NBO Analysis
- 2022
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In: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 10
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Journal article (peer-reviewed)abstract
- The computational modeling supported with experimental results can explain the overall structural packing by predicting the hydrogen bond interactions present in any cocrystals (active pharmaceutical ingredients + coformer) as well as salts. In this context, the hydrogen bonding synthons, physiochemical properties (chemical reactivity and stability), and drug-likeliness behavior of proposed nicotinamide–oxalic acid (NIC–OXA) salt have been reported by using vibrational spectroscopic signatures (IR and Raman spectra) and quantum chemical calculations. The NIC–OXA salt was prepared by reactive crystallization method. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) techniques were used for the characterization and validation of NIC–OXA salt. The spectroscopic signatures revealed that (N7–H8)/(N23–H24) of the pyridine ring of NIC, (C═O), and (C–O) groups of OXA were forming the intermolecular hydrogen bonding (N–H⋯O–C), (C–H⋯O═C), and (N–H⋯O═C), respectively, in NIC–OXA salt. Additionally, the quantum theory of atoms in molecules (QTAIM) showed that (C10–H22⋯O1) and (C26–H38⋯O4) are two unconventional hydrogen bonds present in NIC–OXA salt. Also, the natural bond orbital analysis was performed to find the charge transfer interactions and revealed the strongest hydrogen bonds (N7–H8⋯O5)/(N23–H24⋯O2) in NIC–OXA salt. The frontier molecular orbital (FMO) analysis suggested more reactivity and less stability of NIC–OXA salt in comparison to NIC–CA cocrystal and NIC. The global and local reactivity descriptors calculated and predicted that NIC–OXA salt is softer than NIC–CA cocrystal and NIC. From MESP of NIC–OXA salt, it is clear that electrophilic (N7–H8)/(N23–H24), (C6═O4)/(C3═O1) and nucleophilic (C10–H22)/(C26–H38), (C6–O5)/(C3–O2) reactive groups in NIC and OXA, respectively, neutralize after the formation of NIC–OXA salt, confirming the presence of hydrogen bonding interactions (N7–H8⋯O5–C6) and (N23–H24⋯O2–C3). Lipinski’s rule was applied to check the activeness of salt as an orally active form. The results shed light on several features of NIC–OXA salt that can further lead to the improvement in the physicochemical properties of NIC.
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| 7. |
- Verma, Priya, et al.
(author)
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Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide-oxalic acid (form I) salt by using experimental and theoretical approaches
- 2023
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In: Frontiers in Chemistry. - 2296-2646. ; 11
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Journal article (peer-reviewed)abstract
- In the present work, nicotinamide-oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9...O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy -12.1 kcal mol(-1). Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9...O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol(-1). The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.
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| 8. |
- Verma, Priya, et al.
(author)
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Molecular Structure, Hydrogen Bonding Interactions and Docking Simulations of Nicotinamide (Monomeric and Trimeric Models) by Using Spectroscopy and Theoretical Approach
- 2023
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In: Polycyclic aromatic compounds (Print). - 1040-6638 .- 1563-5333.
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Journal article (peer-reviewed)abstract
- The present work focuses on the structural properties, spectroscopic signatures, intermolecular hydrogen bonding interactions, chemical and biological activity of nicotinamide (NIC) based on its monomeric and trimeric models using density functional theory and vibrational spectroscopy. FT-IR and FT-Raman spectra were obtained using the double-side forward-backward acquisition mode under vacuum. UV-Vis absorption spectra were recorded in methanol and compared with the calculated values. Geometry optimization and vibrational wavenumbers were obtained with the aid of Gaussian 09 program packages. The structural analysis of NIC revealed that the trimeric model was in better agreement with the experimental values than the monomer due to the incorporation of nearest hydrogen bond interactions. Spectroscopic results showed that NH2 and C = O groups of NIC were involved in intermolecular interactions in the trimeric model. The natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses determined the presence, strength as well as nature of the hydrogen bonds were partially covalent. The lesser value of the HOMO-LUMO energy gap for the trimeric model indicated higher reactivity than monomer. Moreover, chemical reactivity was calculated using molecular electrostatic potential surface (MESP) and reactivity descriptors. The docking studies for NIC with several targets explored its biological activity.
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| 9. |
- Verma, Priya, et al.
(author)
-
Vibrational spectra, hydrogen bonding interactions and chemical reactivity analysis of nicotinamide–citric acid cocrystals by an experimental and theoretical approach
- 2019
-
In: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 43:40, s. 15956-15967
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Journal article (peer-reviewed)abstract
- Nicotinamide (NIC), also called vitamin B-3, is commonly known as a pellagra-preventive drug. Citric acid (CA) is a weak tribasic acid, generally used as a flavouring and chelating agent. Herein, a combined experimental and quantum chemical approach was adopted to study the structural properties and spectroscopic signatures of nicotinamide–citric acid (NIC–CA) cocrystals using monomer (2NIC + CA) and cluster (4NIC + CA) models. In the cluster model, two additional NIC molecules were attached to cover the nearest possible interactions to understand the complete molecular geometries and hydrogen bonding interactions present in the cocrystal. In addition to this, our strategy was to calculate and analyse the physicochemical properties of NIC and CA along with improved properties after NIC–CA cocrystal formation. The observed red shift in the stretching modes of CO and N–H of the NH2 groups of NIC and the CO and O–H groups of CA along with the elongation in bond lengths in the cluster model of NIC–CA indicated the presence of hydrogen bonding interactions as well as the formation of cocrystals. Moreover, natural bond orbital (NBO) analysis was performed to obtain information about the interactions that were responsible for the stability and formation of the NIC–CA cocrystal. The ‘quantum theory of atoms in molecules’ (QTAIM) calculations revealed that all the intra- and intermolecular hydrogen bonding interactions present in the NIC–CA (monomer) and NIC–CA (cluster) model were partially covalent in nature. The molecular electrostatic potential (MESP) map of NIC and CA shows that the carbonyl (CO) group and C–N of the pyridine ring in NIC are prone to electrophilic attack, and the hydroxyl (O–H) group of CA is prone to nucleophilic attack. The chemical reactivity parameters calculated using both models show that the NIC–CA cocrystal is more reactive and softer than NIC (API) and CA (co-former) since the band gap of the cocrystal is less than that of both NIC and CA.
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