Rational design of supramolecular chirality in porphyrin assemblies: the halogen bond case

2008 ◽  
pp. 1777 ◽  
Author(s):  
Sankar Muniappan ◽  
Sophia Lipstman ◽  
Israel Goldberg
Keyword(s):  
Rational Design ◽  
Halogen Bond ◽  
Supramolecular Chirality

scholarly journals Rational Design, Synthesis, Characterization and Evaluation of Iodinated 4,4′-Bipyridines as New Transthyretin Fibrillogenesis Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2213 ◽  
Author(s):  
Alessandro Dessì ◽  
Paola Peluso ◽  
Roberto Dallocchio ◽  
Robin Weiss ◽  
Giuseppina Andreotti ◽  
...  
Keyword(s):  
High Performance ◽  
Rational Design ◽  
Halogen Bond ◽  
Coupling Reaction ◽  
Docking Studies ◽  
Binding Modes ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Amyloid Fibril Formation ◽  
The Right

The 3,3′,5,5′-tetrachloro-2-iodo-4,4′-bipyridine structure is proposed as a novel chemical scaffold for the design of new transthyretin (TTR) fibrillogenesis inhibitors. In the frame of a proof-of-principle exploration, four chiral 3,3′,5,5′-tetrachloro-2-iodo-2′-substituted-4,4′- bipyridines were rationally designed and prepared from a simple trihalopyridine in three steps, including a Cu-catalysed Finkelstein reaction to introduce iodine atoms on the heteroaromatic scaffold, and a Pd-catalysed coupling reaction to install the 2′-substituent. The corresponding racemates, along with other five chiral 4,4′-bipyridines containing halogens as substituents, were enantioseparated by high-performance liquid chromatography in order to obtain pure enantiomer pairs. All stereoisomers were tested against the amyloid fibril formation (FF) of wild type (WT)-TTR and two mutant variants, V30M and Y78F, in acid mediated aggregation experiments. Among the 4,4′-bipyridine derivatives, interesting inhibition activity was obtained for both enantiomers of the 3,3′,5,5′-tetrachloro-2′-(4-hydroxyphenyl)-2-iodo-4,4′-bipyridine. In silico docking studies were carried out in order to explore possible binding modes of the 4,4′-bipyridine derivatives into the TTR. The gained results point out the importance of the right combination of H-bond sites and the presence of iodine as halogen-bond donor. Both experimental and theoretical evidences pave the way for the utilization of the iodinated 4,4′-bipyridine core as template to design new promising inhibitors of TTR amyloidogenesis.

Rational Design of an Orthogonal Molecular Interaction System at the Complex Interface of Lung Cancer-Related MDM2 Protein with p53 Peptide

2016 ◽  
Vol 69 (10) ◽  
pp. 1167 ◽  
Author(s):  
Yanwen Li ◽  
Xiyan Yu ◽  
Ying Lou ◽  
Tong Wang
Keyword(s):  
Lung Cancer ◽  
Molecular Interaction ◽  
Rational Design ◽  
Halogen Atom ◽  
Halogen Bond ◽  
Negative Control ◽  
Negative Regulator ◽  
Transactivation Domain ◽  
Interaction System ◽  
Oncogenic Protein

The oncogenic protein MDM2 is an important negative regulator of p53 tumour suppressor. Overexpression of this protein is closely related to the pathological progression and metastasis of lung cancer and other tumours. Previously, a 12-mer peptide segment 17ETFSDLWKLLPE28 (p5317–28) corresponding to residues 17–28 of the human p53 transactivation domain was identified to interact moderately with MDM2. Here, we successfully created an orthogonal molecular interaction system between a native hydrogen bond (H-bond) and a designed halogen bond (X-bond) across the protein–peptide complex interface, where the X-bond was introduced by substituting the 3-hydrogen atom of the benzene ring of the p5317–28 Phe19 residue with a halogen atom X, resulting in a series of 3X-peptides (X = F, Cl, Br or I). Theoretical analysis found that chlorine is a good compromise between X-bonding strength and steric hindrance due to introducing a bulkier halogen atom to the tightly packed complex interface. Consequently, the 3Cl-peptide (Kd = 105 nM) was determined to exhibit ~5-fold affinity improvement relative to p5317–28 (Kd = 570 nM). In contrast, the binding affinity of the 2Cl-peptide (Kd = 492 nM), a negative control that cannot form the X-bond according to computational analysis, did not change considerably on the halogenation.

Molecular tectonics and supramolecular chirality: rational design of hybrid 1-D and 2-D H-bonded molecular networks based on bis-amidinium dication and metal cyanide anions

CrystEngComm ◽  
2002 ◽  
Vol 4 (74) ◽  
pp. 447-453 ◽  
Author(s):  
Sylvie Ferlay ◽  
Véronique Bulach ◽  
Olivier Félix ◽  
Mir Wais Hosseini ◽  
Jean-Marc Planeix ◽  
...  
Keyword(s):  
Rational Design ◽  
Molecular Networks ◽  
Molecular Tectonics ◽  
Metal Cyanide ◽  
Supramolecular Chirality

Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors

2011 ◽  
Vol 54 (15) ◽  
pp. 5607-5611 ◽  
Author(s):  
Zhijian Xu ◽  
Zheng Liu ◽  
Tong Chen ◽  
TianTian Chen ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Rational Design ◽  
Halogen Bond ◽  
Lead Optimization ◽  
Pde5 Inhibitors ◽  
Phosphodiesterase Type

scholarly journals Supramolecular chirality transformation driven by monodentate ligand binding to a coordinatively unsaturated self-assembly based on C3-symmetric ligands

2019 ◽  
Vol 10 (15) ◽  
pp. 4236-4245 ◽  
Author(s):  
Yuki Imai ◽  
Junpei Yuasa
Keyword(s):  
Ligand Binding ◽  
Self Assembly ◽  
Rational Design ◽  
External Stimulus ◽  
Monodentate Ligand ◽  
Supramolecular Chirality ◽  
Dynamic Coordination ◽  
Different Shapes ◽  
Symmetric Ligands

A supramolecular chirality transition driven by monodentate ligand binding, the present strategy shows promise for the rational design of dynamic coordination chirality capable of alternating between chiral objects of different shapes driven by a specific external stimulus.

scholarly journals Rational Design of a Photoswitchable DNA Glue Enabling High Regulatory Function and Supramolecular Chirality Transfer

2021 ◽  
Author(s):  
Nadja Simeth ◽  
Shotaro Kobayashi ◽  
Piermichele Kobauri ◽  
Stefano Crespi ◽  
Wiktor Szymanski ◽  
...  
Keyword(s):  
Rational Design ◽  
Regulatory Function ◽  
Duplex Dna ◽  
Base Pairs ◽  
Chirality Transfer ◽  
Complementary Dna ◽  
Spontaneous Formation ◽  
Supramolecular Chirality

Short, complementary DNA single strands with mismatched base pairs cannot undergo spontaneous formation of duplex DNA (dsDNA). Mismatch binding ligands (MBLs) can compensate this effect, inducing the formation of the...

Crystalline assemblies of porphyrins with mixed bromophenyl and pyridyl meso-substituents and manifestation of supramolecular chirality induced by inter-porphyrin Br⋯N halogen bonds

2011 ◽  
Vol 15 (11n12) ◽  
pp. 1250-1257 ◽  
Author(s):  
Hatem M. Titi ◽  
Anirban Karmakar ◽  
Israel Goldberg
Keyword(s):  
Self Assembly ◽  
Halogen Bond ◽  
Supramolecular Assembly ◽  
Halogen Bonding ◽  
Building Blocks ◽  
Zinc Ion ◽  
Halogen Bonds ◽  
X Ray Diffraction ◽  
Supramolecular Chirality ◽  
Porphyrin Core

Four new crystalline solids based on the zinc-5,15-bis(4′-bromophenyl)-10,20- bis(4′-pyridyl)porphyrin ( Zn –DBDPyP) and zinc/copper-5,10,15-tris(4′-bromophenyl)-20-(4′-pyridyl)-porphyrin ( Zn/Cu –TBMPyP) platforms as building blocks, have been prepared and structurally analyzed by X-ray diffraction in order to examine whether the Br⋯N halogen bond can be effective in directing the supramolecular assembly of this functionalized porphyrins, in a similar way observed earlier for their iodophenyl-substituted analogs. The zinc ion in the porphyrin core was protected by an external ligand (pyridyl or methanol) to prevent its possible coordination to the pyridyl-porphyrin substituents. Neither the bis-pyridyl Zn (py)–DBDPyP scaffold nor the Zn(MeOH)/Cu –TBMPyP exhibited inter-porphyrin halogen bonding in their corresponding crystals. Only the layered self-assembly of the Zn (py)–TBMPyP building block was found to be uniquely directed by Br⋯N halogen bonds, as well as by Br⋯Br and Br⋯π interactions. This observation supports our notion that asymmetric functionalization of the tetraarylporphyrin scaffold, combined with directional interporphyrin interactions (as halogen bonding), represent a promising approach to supramolecular chirality.

scholarly journals Halogen bonding stabilizes acis-azobenzene derivative in the solid state: a crystallographic study

2017 ◽  
Vol 73 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Marco Saccone ◽  
Antti Siiskonen ◽  
Franisco Fernandez-Palacio ◽  
Arri Priimagi ◽  
Giancarlo Terraneo ◽  
...  
Keyword(s):  
Solid State ◽  
Density Functional ◽  
Rational Design ◽  
Halogen Bond ◽  
Phase Segregation ◽  
Halogen Bonding ◽  
Density Functional Theory Calculations ◽  
Aliphatic Chain ◽  
Molecular Arrangement

Crystals oftrans- andcis-isomers of a fluorinated azobenzene derivative have been prepared and characterized by single-crystal X-ray diffraction. The presence of F atoms on the aromatic core of the azobenzene increases the lifetime of the metastablecis-isomer, allowing single crystals of thecis-azobenzene to be grown. Structural analysis on thecis-azobenzene, complemented with density functional theory calculations, highlights the active role of the halogen-bond contact (N...I synthon) in promoting the stabilization of thecis-isomer. The presence of a long aliphatic chain on the azobenzene unit induces a phase segregation that stabilizes the molecular arrangement for both thetrans- andcis-isomers. Due to the rarity ofcis-azobenzene crystal structures in the literature, our paper makes a step towards understanding the role of non-covalent interactions in driving the packing of metastable azobenzene isomers. This is expected to be important in the future rational design of solid-state, photoresponsive materials based on halogen bonding.

Rational design of an orthogonal noncovalent interaction system at the MUPP1 PDZ11 complex interface with CaMKIIα-derived peptides in human fertilization

2017 ◽  
Vol 13 (10) ◽  
pp. 2145-2151 ◽  
Author(s):  
Yi-Le Zhang ◽  
Zhao-Feng Han
Keyword(s):  
Hydrogen Bond ◽  
Rational Design ◽  
Halogen Bond ◽  
Noncovalent Interaction ◽  
Rational Approach ◽  
Interaction System ◽  
Human Fertilization

An orthogonal noncovalent interaction (ONI) system between a native hydrogen bond and a designed halogen bond across the complex interface of the MUPP1 PDZ11 domain with the CaMKIIαsia[Asn-1Phe] peptide mutant is introduced using a structure-based rational approach.

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