scholarly journals Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies

2021 ◽  
Vol 11 (7) ◽  
pp. 3113
Author(s):  
Silvia Bordoni ◽  
Stefano Cerini ◽  
Riccardo Tarroni ◽  
Magda Monari ◽  
Gabriele Micheletti ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Metal Ion ◽  
Theoretical Studies ◽  
Binding Modes ◽  
Hydrogen Binding ◽  
Nmr Studies ◽  
X Ray ◽  
Structure Activity ◽  
Experimental And Theoretical Studies ◽  
Shed Light

Ruthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. This report deals with the reaction between dihydride ruthenium mer-[Ru(H)2(CO)(PPh3)3], 1 and the thymine acetic acid (THAcOH) selected as model for nucleobase derivatives. The reaction in refluxing toluene between 1 and THAcOH excess, by H2 release affords the double coordinating species κ1-(O)THAc-, κ2-(O,O)THAc-[Ru(CO)(PPh3)2], 2. The X-ray crystal structure confirms a simultaneous monohapto, dihapto- THAc coordination in a reciprocal facial disposition. Stepwise additions of THAcOH allowed to intercept the monohapto mer-κ1(O)THAc-Ru(CO)H(PPh3)3] 3 and dihapto trans(P,P)-κ2(O,O)THAc-[Ru(CO)H(PPh3)2] 4 species. Nuclear magnetic resonance (NMR) studies, associated with DFT (Density Function Theory)-calculations energies and analogous reactions with acetic acid, supported the proposed reaction path. As evidenced by the crystal supramolecular hydrogen-binding packing and 1H NMR spectra, metal coordination seems to play a pivotal role in stabilizing the minor [(N=C(OH)] lactim tautomers, which may promote mismatching to DNA nucleobase pairs as a clue for its anticancer activity.

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

Structural studies on monofluorinated derivatives of the phytohormone indole-3-acetic acid (auxin)

1996 ◽  
Vol 52 (4) ◽  
pp. 651-661 ◽  
Author(s):  
A. Antolić ◽  
B. Kojić-Prodić ◽  
S. Tomić ◽  
B. Nigović ◽  
V. Magnus ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Side Chain ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
Molecular Conformations ◽  
X Ray ◽  
Structure Activity ◽  
Planar Conformation ◽  
Derivatives Of ◽  
Indole 3 Acetic Acid

As part of the molecular recognition studies on the phytohormone indole-3-acetic acid (IAA) a series of fluorinated IAA's has been examined. The phenyl ring substitution at positions 4, 5, 6 and 7 resulted in four compounds, which were analyzed. Structure–activity correlation includes the analysis of their molecular conformations, based on the X-ray diffraction and computational chemistry results, and bioactivity determinations in the Avena coleoptile and the Pisum sativum stem straight-growth tests, lipophilicity and UV absorbance. The conformations of monofluorinated IAA's and a free hormone are defined by rotations about two bonds: one describes the relative orientation of a side chain towards the indole plane and the second the orientation of the carboxylic group. The results of X-ray structure analysis revealed the folded shape of the molecules in all compounds studied. Molecular mechanics and dynamics located the folded conformation as the local minimum, but failed to detect the planar conformation as one of the local minima, which according to ab initio results on IAA and 4-CI-IAA could also be possible. Crystal data at 295 K for 4-F-IAA and at 297 K for 5-F-IAA, and at 100 K for 6-F-IAA and 7-F-IAA using Mo Kα radiation (λ = 0.71073 Å) and Cu Kα (λ = 1.5418 Å, for 7-F-IAA), are as follows: 4-F-IAA, C10H8NO2F, Mr = 193.18, monoclinic, C2/c, a = 17.294 (5), b = 13.875 (4), c = 7.442 (4) Å, β = 103.88 (6)°, V = 1734 (1) Å3, Z = 8, Dx = 1.480 g cm−3, μ = 1.1 cm−1, F(000) = 800, R = 0.043, wR = 0.044 for 823 symmetry-independent [I ≥ 3σ(I)] reflections; 5-F-IAA, C10H8NO2F, monoclinic, P21/c, a = 19.284 (5), b = 5.083 (4), c = 9.939 (4) Å, β = 117.28 (6)°, V = 865.9 (1) Å3, Z = 4, Dx = 1.482 g cm−3, μ = 1.1  cm−1, F(000) = 400, R = 0.062, wR = 0.057 for 729 symmetry-independent [I ≥ 3σ(I)] reflections; 6-F-IAA, C10H8NO2F, monoclinic, P21/a, a = 9.360 (1), b = 5.167 (4), c = 17.751 (4) Å, β = 93.75 (1)°, V = 856.7 (8) Å3, Z = 4, Dx = 1.498 g cm−3, μ = 1.1 cm−1, F(000) = 400, R = 0.048, wR = 0.048 for 1032 symmetry-independent [I ≥ 2σ(I)] reflections; 7-F-IAA, C10H8NO2F, monoclinic, P21/a, a = 9.935 (5), b = 5.0059 (4), c = 17.610 (1) Å, β = 102.13 (1)°, V = 856.3 (1) Å3, Z = 4, Dx = 1.498 g cm−3, μ = 9.8 cm−1 (Cu Kα, F(000) = 400, R = 0.035, wR = 0.040 for 1504 symmetry-independent [I ≥ 2σ(I)] reflections.

Experimental and theoretical studies of the mica polymorphs

1956 ◽  
Vol 31 (234) ◽  
pp. 209-235 ◽  
Author(s):  
J. V. Smith ◽  
H. S. Yoder
Keyword(s):  
Growth Mechanism ◽  
Theoretical Study ◽  
Dominant Role ◽  
Spiral Growth ◽  
Theoretical Studies ◽  
X Ray ◽  
Layer Cell ◽  
Triclinic Structure ◽  
Experimental And Theoretical Studies ◽  
Made In

SummaryAn experimental and theoretical study has been made in order to determine the number and the structure of the possible polymorphs and to determine the structural relations between them. The simplest structures are 1M, 2M1, 2M2, 3T, 20, and 6H polymorphs, and more complicated types can be developed. Some of the previously described polymorphs were not contained in the theoretical list and were re-examined. The 6M structure was found to be a 2M2 polymorph, the 6-layer triclinic type was found to be a 2M1 polymorph, and the 3M structure was shown to be a 3T type. The 24-layer triclinic structure could be described on a simpler 8-layer cell. This type together with a new 12-layer monoclinic structure, as well as other structures of higher periodicity, presumably consists of complex stacking and results from spiral-growth mechanism. Two extreme types of layer-disordered crystals may be built and a disorder of individual ions may also occur. Single stacking faults result in twinned crystals. A new twin relation (180° rotation about the [100] axis) has been recognized. Twenty specimens from extreme geological environments have been examined in order to evaluate the control of environment on the stacking. The type of stacking could not be attributed solely to the influence of pressure and temperature. Composition appears to play a dominant role in the type of stacking, and semi-quantitative structural arguments appear to support this contention. The influence of growth mechanism is discussed. A scheme for the identification of the mica polymorphs by X-ray powder and single-crystal methods is given.

Experimental and theoretical studies of the physical processes occurring in thin plane targets irradiated by intense X-ray pulses

2007 ◽  
Vol 33 (6) ◽  
pp. 444-454 ◽  
Author(s):  
A. É. Bugrov ◽  
I. N. Burdonskiĭ ◽  
V. V. Gavrilov ◽  
A. Yu. Gol’tsov ◽  
E. V. Grabovskiĭ ◽  
...  
Keyword(s):  
Theoretical Studies ◽  
Physical Processes ◽  
X Ray ◽  
Experimental And Theoretical Studies

scholarly journals Atypical interactions between GCPII and hydroxamate-based inhibitors

2014 ◽  
Vol 70 (a1) ◽  
pp. C805-C805
Author(s):  
Zora Novakova ◽  
Jitka Barinkova ◽  
Barbara Slusher ◽  
Pavel Majer ◽  
Cyril Barinka
Keyword(s):  
Prostate Cancer ◽  
Neurological Disorders ◽  
High Specificity ◽  
Structural Data ◽  
Mechanistic Explanation ◽  
Zinc Binding ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Glutamate Carboxypeptidase

Human glutamate carboxypeptidase II (GCPII) is a zinc-dependent metallopeptidase implicated in diverse pathologies. GCPII-specific ligands can be used in diagnostic and therapeutic applications in prostate cancer and various neurological disorders [1]. Such ligands typically consist of a glutamate moiety linked to a zinc-binding group to ensure high specificity and affinity, respectively [2]. Hydroxamate functionality is one of the prominent zinc-binding functions used in the field, however, there are no structural data describing interactions between hydroxamates and GCPII. Here we report X-ray structures of six complexes between GCPII and hydroxamate-based inhibitors. Our structures reveal unexpected positioning of hydroxamates in the internal GCPII pocket that differs markedly from binding modes of matching prototypical GCPII inhibitors featuring different zinc-binding groups. They provide mechanistic explanation for prior structure-activity relationship studies and can be exploited for the structure-assisted design of novel GCPII-specific compounds.

Experimental and Theoretical Studies on 1,4,5,7-Dithiadiazepinyl Radicals:  Preparation and X-ray Structure of 5-(Trimethylsilyl)tetrachlorobenzo-1,4,5,7-dithiadiazepine

1997 ◽  
Vol 36 (21) ◽  
pp. 4772-4777 ◽  
Author(s):  
Vadapalli Chandrasekhar ◽  
Tristram Chivers ◽  
Masood Parvez ◽  
Ignacio Vargas-Baca ◽  
Tom Ziegler
Keyword(s):  
Theoretical Studies ◽  
X Ray ◽  
Experimental And Theoretical Studies

X-ray near-edge structure of the II-VI compounds containing manganese: Experimental and theoretical studies ofCd1−xMnxTe andZn1−xMnxTe

1991 ◽  
Vol 44 (20) ◽  
pp. 11075-11084 ◽  
Author(s):  
A. Kisiel ◽  
A-I. Ali Dahr ◽  
P. M. Lee ◽  
G. Dalba ◽  
P. Fornasini ◽  
...  
Keyword(s):  
Theoretical Studies ◽  
Edge Structure ◽  
X Ray ◽  
Experimental And Theoretical Studies
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