scholarly journals New Crystal Forms for Biologically Active Compounds. Part 1: Noncovalent Interactions in Adducts of Nevirapine with XB Donors

Crystals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 71 ◽  
Author(s):  
Mariya Kryukova ◽  
Alexander Sapegin ◽  
Alexander Novikov ◽  
Mikhail Krasavin ◽  
Daniil Ivanov
Keyword(s):  
Noncovalent Interactions ◽  
Physiological Activity ◽  
Topological Analysis ◽  
Antiviral Drug ◽  
Halogen Bonding ◽  
Active Pharmaceutical Ingredient ◽  
Biologically Active ◽  
Crystal Forms ◽  
Crystalline Forms ◽  
Supramolecular Contacts

Stabilization of specific crystal polymorphs of an active pharmaceutical ingredient is crucial for preventing uncontrollable interconversion of various crystalline forms, which affects physicochemical properties as well as physiological activity. Co-crystallization with various excipients is an emerging productive way of achieving such stabilization in the solid state. In this work, we identified an opportunity for co-crystallization of antiviral drug nevirapine (NVP) with a classical XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (1,4-FIB), as well as 1,3-diiodobenzene (1,3-DIB), which has been seldom employed as an XB donor to date. In the X-ray structures of NVP·1,4-FIB and NVP·1,3-DIB co-crystals, different hydrogen and halogen bonding modes were detected and further investigated via DFT calculations as well as topological analysis of the electron density distribution within the framework of the QTAIM method at the M06/DZP-DKH level of theory. Estimated energies of these supramolecular contacts vary from 0.6 to 5.7 kcal/mol.

Non-covalent interactions observed in nevirapinium pentaiodide hydrate which include the rare I4–I−···O=C halogen bonding

2019 ◽  
Vol 234 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Mariya A. Kryukova ◽  
Alexander V. Sapegin ◽  
Alexander S. Novikov ◽  
Mikhail Krasavin ◽  
Daniil M. Ivanov
Keyword(s):  
Topological Analysis ◽  
Antiviral Drug ◽  
Halogen Bonding ◽  
Molecular Iodine ◽  
Salt Form ◽  
Hydrogen Bonding Interactions ◽  
Non Covalent Interactions ◽  
Crystalline Forms ◽  
Covalent Interactions ◽  
Hydrate Salt

Abstract In the course of screening for novel crystalline forms of antiviral drug nevirapine, co-crystallization of the latter with molecular iodine was attempted. This resulted in the formation of a hydrate salt form composed of the protonated nevirapinium cation and pentaiodide anion. In the X-ray structure of NVPH+I5−·H2O, halogen and hydrogen bonding interactions were identified and studied by DFT calculations and topological analysis of the electron density distribution within the framework of QTAIM method at the B3LYP/DZP-DKH and M06/DZP-DKH levels of theory. Estimated energies of these contacts are 1.3–9.4 kcal/mol.

scholarly journals New Crystal Forms for Biologically Active Compounds. Part 2: Anastrozole as N-Substituted 1,2,4-Triazole in Halogen Bonding and Lp-π Interactions with 1,4-Diiodotetrafluorobenzene

Crystals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 371 ◽  
Author(s):  
Mariya A. Kryukova ◽  
Alexander V. Sapegin ◽  
Alexander S. Novikov ◽  
Mikhail Krasavin ◽  
Daniil M. Ivanov
Keyword(s):  
Quantum Chemical ◽  
Halogen Bonding ◽  
Active Pharmaceutical Ingredient ◽  
Biologically Active ◽  
Second Line Therapy ◽  
Crystal Forms ◽  
X Ray ◽  
Line Therapy ◽  
Non Covalent Interactions ◽  
Covalent Interactions

For an active pharmaceutical ingredient, it is important to stabilize its specific crystal polymorph. If the potential interconversion of various polymorphs is not carefully controlled, it may lead to deterioration of the drug’s physicochemical profile and, ultimately, its therapeutic efficacy. The desired polymorph stabilization can be achieved via co-crystallization with appropriate crystallophoric excipients. In this work, we identified an opportunity for co-crystallization of anastrozole (ASZ), a well-known aromatase inhibitor useful in second-line therapy of estrogen-dependent breast cancer, with a classical XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (1,4-FIB). In the X-ray structures of ASZ·1.5 (1,4-FIB) co-crystal, different non-covalent interactions involving hydrogen and halogen atoms were detected and studied by quantum chemical calculations and QTAIM analysis at the ωB97XD/DZP-DKH level of theory.

scholarly journals Halogen Bonding Provides Heterooctameric Supramolecular Aggregation of Diaryliodonium Thiocyanate

Crystals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 230
Author(s):  
Natalia S. Soldatova ◽  
Vitalii V. Suslonov ◽  
Troyana Yu. Kissler ◽  
Daniil M. Ivanov ◽  
Alexander S. Novikov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Density Functional Theory ◽  
Electron Density Distribution ◽  
Density Functional ◽  
Noncovalent Interactions ◽  
Topological Analysis ◽  
Halogen Bonding ◽  
State Structure ◽  
Functional Theory ◽  
Supramolecular Aggregation

The crystal structure of the newly synthesized 4-methoxyphenyl(phenyl)iodonium thiocyanate, [PhI(4-C6H4OMe)](SCN), represents the first example of 16-membered cyclic heterooctamer formed by halogen bonding between the iodonium cation and SCN−. Results of density functional theory (DFT) calculations followed by the topological analysis of the electron density distribution within the framework of the quantum theory of atoms in molecules (QTAIM) method at the ωB97XD/DZP-DKH level of theory reveal that energies of attractive intermolecular noncovalent interactions I···S and I···N (responsible for the formation of heterooctameric supramolecular clusters {PhI(4-C6H4OMe)}4·{SCN}4 in the solid state structure of [PhI(4-C6H4OMe)](SCN)) vary from 0.9 to 8.5 kcal/mol.

The X40x10 Halogen Bonding Benchmark Revisited: Surprising Importance of (n-1)d Subvalence Correlation

2017 ◽  
Author(s):  
Manoj Kumar Kesharwani ◽  
Nitai Sylvetsky ◽  
Debashree Manna ◽  
Jan M.L. Martin
Keyword(s):  
Dissociation Energy ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Coupled Cluster ◽  
Dissociation Energies ◽  
Iodine Species ◽  
Explicitly Correlated ◽  
High Level ◽  
Cluster Methods ◽  
Small Separation

<p>We have re-evaluated the X40x10 benchmark for halogen bonding using conventional and explicitly correlated coupled cluster methods. For the aromatic dimers at small separation, improved CCSD(T)–MP2 “high-level corrections” (HLCs) cause substantial reductions in the dissociation energy. For the bromine and iodine species, (n-1)d subvalence correlation increases dissociation energies, and turns out to be more important for noncovalent interactions than is generally realized. As in previous studies, we find that the most efficient way to obtain HLCs is to combine (T) from conventional CCSD(T) calculations with explicitly correlated CCSD-F12–MP2-F12 differences.</p>

An insight to the noncovalent interactions in two triamine based mononuclear iron(III) Schiff base complexes with special emphasis on the formation of Br•••π halogen bonding

CrystEngComm ◽  
2021 ◽  
Author(s):  
Shouvik Chattopadhyay ◽  
Tanmoy Basak ◽  
Antonio Frontera
Keyword(s):  
Schiff Base ◽  
Solid State ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Schiff Base Complexes ◽  
X Ray ◽  
Mononuclear Iron

Two mononuclear iron(III) complexes, [FeL1Cl]∙CH3CN (1) and [FeL2(N3)] (2) {H2L1= N,N′-bis(5-chlorosalicylidene)diethylenetriamine and H2L2= N,N′-bis(5-bromosalicylidene)diethylenetriamine}, have been synthesized and characterized by X-ray crystallographic studies. In the solid state, there are strong...

scholarly journals Born out of Fire and Ice: Polymorph Studies of the Antiviral Famciclovir

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 129
Author(s):  
Liana Vella-Zarb ◽  
Ulrich Baisch
Keyword(s):  
Variable Temperature ◽  
Chemical Properties ◽  
Crystal Form ◽  
X Ray Diffraction ◽  
Crystal Forms ◽  
X Ray ◽  
Physical Chemical ◽  
Diffraction Patterns ◽  
Crystalline Forms

There is much interest and focus on solid forms of famciclovir. However, in spite of the abundance of reported differences in oral bioavailability, compressibility, and other physical–chemical properties of the various crystal forms of this drug, very little precise structural analysis is available in the literature to date. The form used in the commercial formulation is the anhydrous form I. Patents and patent applications report three different anhydrous crystalline forms on the basis of unindexed powder diffraction patterns. Single-crystal and variable-temperature X-ray diffraction experiments using the commercially available anhydrous form of famciclovir were carried out and led not only to the crystal structure determination of the anhydrous form I, but also to discovery of a new crystal form of anhydrous famciclovir from powder data.

The Possibility of Predicting Prolongation of the Pharmacological Action of Biologically Active Polymeric Substances

2012 ◽  
Vol 39 (11) ◽  
pp. 21-27 ◽  
Author(s):  
L.I. Shal'nova ◽  
N.A. Lavrov ◽  
A.F. Nikolaev
Keyword(s):  
Dissociation Constants ◽  
Equilibrium Dialysis ◽  
Physiological Activity ◽  
Pharmacological Action ◽  
Physicochemical Characteristics ◽  
Biologically Active ◽  
Organic Bases ◽  
Physiologically Active Substances ◽  
Biological Methods ◽  
The Relationship

The physicochemical properties and the formation, stability, and dissociation constants of complexes of poly acids with organic bases possessing physiological activity were determined by methods of potentiometric titration, conductometry, and equilibrium dialysis, and by biological methods. The relationship between the level of physicochemical characteristics of complexes and the possibility of predicting the prolonged pharmacological (antimicrobial, anaesthetising) action of physiologically active substances in complexes with polymers was established.

Doxycycline hydrate and doxycycline hydrochloride dihydrate – crystal structure and charge density analysis

2018 ◽  
Vol 233 (9-10) ◽  
pp. 649-661 ◽  
Author(s):  
Daniel Tchoń ◽  
Anna Makal ◽  
Matthias Gutmann ◽  
Krzysztof Woźniak
Keyword(s):  
Charge Density ◽  
Topological Analysis ◽  
Crystal Form ◽  
X Ray Diffraction ◽  
Neutron Data ◽  
Distribution Models ◽  
Crystal Forms ◽  
Density Analysis ◽  
Resonance Assisted Hydrogen Bond ◽  
Amide Nitrogen Atom

Abstract High-resolution low-temperature X-ray diffraction experiments for doxycycline monohydrate and hydrochloride dihydrate have been performed. Translation-Libration-Screw (TLS) analysis for both crystal forms as well as the data from neutron diffraction experiment for hydrochloride combined with the Hansen-Coppens formalism resulted in precise charge density distribution models for both the zwitterionic monohydrate and a protonated hydrochloride crystal forms. Their detailed topological analysis suggested that the electron structure of doxycycline’s amide moiety undergoes significant changes during protonation due to formation of a very strong resonance-assisted hydrogen bond. A notably increased participation of amide nitrogen atom and hydrogen-accepting oxygen atom in the resonance upon doxycycline protonation was observed. A comparison of TLS- and neutron data-derived hydrogen parameters confirmed the experimental neutron data to be vital for proper description of intra- and inter-molecular interactions in this compound. Finally, calculated lattice and interaction energies quantified repulsive Dox-Dox interactions in the protonated crystal form of the antibiotic, relating with a good solubility of doxycycline hydrochloride relative to its hydrate.

scholarly journals Halogen Bonding: An Underestimated Player in Membrane–drug Interactions

2020 ◽  
Author(s):  
Rafael Nunes ◽  
Diogo Vila Viçosa ◽  
Paulo J. Costa
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Noncovalent Interactions ◽  
Halogen Bonding ◽  
Lewis Bases ◽  
Protein Ligand Interactions ◽  
Biochemical Systems ◽  
Ligand Interactions ◽  
Dynamics Simulations

<div>Halogen bonds (HaBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to modulate protein–ligand interactions. In this work, we report evidence for the existence of HaB-mediated halogen–phospholipid recognition phenomena as our molecular dynamics simulations support the existence of favorable interactions between halobenzene derivatives and both phosphate (PO) or ester (CO) oxygen acceptors from model phospholipid bilayers, thus providing insights into the role of HaBs in driving the permeation of halogenated drug like molecules across biological membranes. This represents a relevant molecular mechanism, previously overlooked, determining the pharmacological activity of halogenated molecules with implications in drug discovery and development, a place where halogenated molecules account for a significant part of the chemical space. Our data also shows that, as the ubiquitous hydrogen bond, HaBs should be accounted for in the development of membrane permeability models.</div>

Intermolecular hydrogen bonding H···Cl in crystal structure of palladium(II)-bis(diaminocarbene) complex

2019 ◽  
Vol 234 (3) ◽  
pp. 155-164 ◽  
Author(s):  
Mikhail A. Kinzhalov ◽  
Sergey V. Baykov ◽  
Alexander S. Novikov ◽  
Matti Haukka ◽  
Vadim P. Boyarskiy
Keyword(s):  
Crystal Packing ◽  
Solid Phase ◽  
Topological Analysis ◽  
X Ray Diffraction ◽  
Intermolecular Hydrogen Bonds ◽  
X Ray ◽  
Intermolecular Contacts ◽  
Organometallic Cations ◽  
Supramolecular Contacts ◽  
Moderate Yield

Abstract The reaction of bis(isocyanide)palladium complex cis-[PdCl2(CNXyl)2] (Xyl=2,6-Me2C6H3) with excess of 4,5-dichlorobenzene-1,2-amine in a C2H4Cl2/MeOH mixture affords monocationic bis(diaminocarbene) complex cis-[PdClC{(NHXyl)=NHC6H2Cl2NH2}{C(NHXyl)=NHC6H2Cl2NH2}]Cl (3) in moderate yield (42%). Complex 3 exists in the solid phase in the H-bonded dimeric associate of two single charged organometallic cations and two chloride anions according to X-ray diffraction data. The Hirshfeld surface analysis for the X-ray structure of 3 reveals that the crystal packing is determined primarily by intermolecular contacts H–Cl, H–H, and H–C. The intermolecular hydrogen bonds N–H···Cl and C–H···Cl in the H-bonded dimeric associate of 3 were studied by DFT calculations and topological analysis of the electron density distribution within the framework of QTAIM method, and estimated energies of these supramolecular contacts vary from 1.6 to 9.1 kcal/mol. Such non-covalent bonding means that complex 3 is an anionic receptor for the chloride anions.

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