Designed Synthesis of a 1D Polymer in Twist-Stacked Topology via Single-Crystal-to-Single-Crystal Polymerization

To synthesize a fully organic 1D polymer in a novel twist-stacked topology, we designed a peptide monomer HC≡CCH₂-NH-Ile-Leu-N₃, which crystallizes with its molecules H-bonded along a six-fold screw axis. These H-bonded columns pack parallelly such that molecules arrange head-to-tail, forming linear non-covalent chains in planes perpendicular to the screw axis. The chains arrange parallelly to form molecular layers which twist-stack along the screw axis. Crystals of this monomer, on heating, undergo single-crystal-to-single-crystal (SCSC) topochemical azide–alkyne cycloaddition (TAAC) polymerization to yield an exclusively 1,4-triazole-linked polymer in a twist-stacked layered topology. This topologically defined polymer shows better mechanical strength and thermal stability than its unordered form, as evidenced by nanoindentation studies and thermogravimetric analysis, respectively. This work illustrates the scope of topochemical polymerizations for synthesizing polymers in pre-decided topologies.     

Spontaneous Single‐Crystal‐to‐Single‐Crystal Evolution of Two Cross‐Laminated Polymers

Two cases of spontaneous evolution of monomers to linear polymers having novel cross‐laminated topology are reported. We synthesized two peptide monomers N₃‐Gly‐Gly‐NH‐CH₂‐CCH and N₃‐Gly‐Gly‐Gly‐CH₂‐CCH and solved their crystal structures by single‐crystal X‐ray diffraction. They adopt H‐bonded crisscrossed layered packing in their crystals such that: (a) the monomers are aligned head‐to‐tail in 1D‐chain‐like arrays and parallel arrangement of such arrays forms a layer; (b) the proximally placed azide and alkyne motifs are in an orientation apt for their regiospecific cycloaddition; (c) each monomer having x peptide bonds is H‐bonded with 2x monomers disposed in intersecting arrangement, which pre‐organize 1D‐chain‐like arrays in adjacent layers in perpendicular orientation. These crystals underwent spontaneous single‐crystal‐to‐single‐crystal (SCSC) polymerization via azide–alkyne cycloaddition reaction to form triazolyl‐polyglycines, at room temperature. The crisscrossed arrangement of monomers in adjacent layers ensured the formation of cross‐laminated polymers.     

Two crystalline modifications of 2‐­hydroxy­cyclo­pent‐2‐enone

The orthorhombic form of 2‐hydroxy­cyclo­pent‐2‐enone, C₅H₆O₂, consists of chains of hydrogen‐bonded mol­ecules aligned along a twofold screw axis. The monoclinic form contains two independent mol­ecules, which have different orientations of the hydroxyl proton, and which assemble into ribbons along a twofold screw axis.     

β‐Sheet to Helical‐Sheet Evolution Induced by Topochemical Polymerization: Cross‐α‐Amyloid‐like Packing in a Pseudoprotein with Gly‐Phe‐Gly Repeats

Protein‐mimics are of great interest for their structure, stability, and properties. We are interested in the synthesis of protein‐mimics containing triazole linkages as peptide‐bond surrogate by topochemical azide‐alkyne cycloaddition (TAAC) polymerization of azide‐ and alkyne‐modified peptides. The rationally designed dipeptide N₃‐CH₂CO‐Phe‐NHCH₂CCH ( 1 ) crystallized in a parallel β‐sheet arrangement and are head‐to‐tail aligned in a direction perpendicular to the β‐sheet‐direction. Upon heating, crystals of 1 underwent single‐crystal‐to‐single‐crystal polymerization forming a triazole‐linked pseudoprotein with Gly‐Phe‐Gly repeats. During TAAC polymerization, the pseudoprotein evolved as helical chains. These helical chains are laterally assembled by backbone hydrogen bonding in a direction perpendicular to the helical axis to form helical sheets. This interesting helical‐sheet orientation in the crystal resembles the cross‐α‐amyloids, where α‐helices are arranged laterally as sheets.     

Synthesis and Reversible Hydration of a Pseudoprotein,a Fully Organic Polymeric Desiccant by Multiple Single‐Crystal‐to‐Single‐Crystal Transformations

A diphenylalanine derivative, N3‐Phe‐Phe‐NHCH2CCH, was designed for topochemical azide–alkyne cycloaddition (TAAC) polymerization. This dipeptide adopted β‐sheet arrangement as designed, in its crystals, but the azide and alkyne were not fitly aligned for their topochemical reaction. However, the voids present around these groups allowed them to attain a reactive geometry upon heating and their consequent TAAC polymerization to a pseudoprotein in a single‐crystal‐to‐single‐crystal (SCSC) fashion. This motion led to the creation of channels in the product crystal and it absorbed water from the surroundings to fill these channels as H‐bonded water wire. The pseudoprotein undergo reversible hydration/dehydration in SCSC fashion many times under mild conditions: hydration at low relative humidity and dehydration at low temperature. Vapor sorption analyses suggest that this fully organic polymer might be useful as an energy‐efficient desiccant material for controlling indoor humidity.     

Similarities and differences in the structures of 5‐bromo‐6‐hydroxy‐7,8‐dimethylchroman‐2‐one and 6‐hydroxy‐7,8‐dimethyl‐5‐nitrochroman‐2‐one

The title compounds, C₁₁H₁₁BrO₃, (I), and C₁₁H₁₁NO₅, (II), respectively, are derivatives of 6‐hydroxy‐5,7,8‐trimethylchroman‐2‐one substituted at the 5‐position by a Br atom in (I) and by a nitro group in (II). The pyranone rings in both molecules adopt half‐chair conformations, and intramolecular O—H...Br [in (I)] and O—H...O_nitro [in (II)] hydrogen bonds affect the dispositions of the hydroxy groups. Classical intermolecular O—H...O hydrogen bonds are found in both molecules but play quite dissimilar roles in the crystal structures. In (I), O—H...O hydrogen bonds form zigzag C(9) chains of molecules along the a axis. Because of the tetragonal symmetry, similar chains also form along b. In (II), however, similar contacts involving an O atom of the nitro group form inversion dimers and generate R₂²(12) rings. These also result in a close intermolecular O...O contact of 2.686 (4) Å. For (I), four additional C—H...O hydrogen bonds combine with π–π stacking interactions between the benzene rings to build an extensive three‐dimensional network with molecules stacked along the c axis. The packing in (II) is much simpler and centres on the inversion dimers formed through O—H...O contacts. These dimers are stacked through additional C—H...O hydrogen bonds, and further weak C—H...O interactions generate a three‐dimensional network of dimer stacks.     

Synthesis and Reversible Hydration of a Pseudoprotein,a Fully Organic Polymeric Desiccant by Multiple Single‐Crystal‐to‐Single‐Crystal Transformations

A diphenylalanine derivative, N3‐Phe‐Phe‐NHCH2CCH, was designed for topochemical azide–alkyne cycloaddition (TAAC) polymerization. This dipeptide adopted β‐sheet arrangement as designed, in its crystals, but the azide and alkyne were not fitly aligned for their topochemical reaction. However, the voids present around these groups allowed them to attain a reactive geometry upon heating and their consequent TAAC polymerization to a pseudoprotein in a single‐crystal‐to‐single‐crystal (SCSC) fashion. This motion led to the creation of channels in the product crystal and it absorbed water from the surroundings to fill these channels as H‐bonded water wire. The pseudoprotein undergo reversible hydration/dehydration in SCSC fashion many times under mild conditions: hydration at low relative humidity and dehydration at low temperature. Vapor sorption analyses suggest that this fully organic polymer might be useful as an energy‐efficient desiccant material for controlling indoor humidity.     

Two polymorphs of N‐(2,6‐difluorophenyl)formamide

The structures of two distinct polymorphic forms of N‐(2,6‐difluorophenyl)formamide, C₇H₅F₂NO, have been studied using single crystals obtained under different crystallizing conditions. The two forms crystallize in different space groups, viz. form (Ia) in the orthorhombic Pbca and form (Ib) in the monoclinic P2₁ space group. Each polymorph crystallizes with one complete molecule in the asymmetric unit and they have a similar molecular geometry, showing a trans conformation with the formamide group being out of the plane of the aromatic ring. The packing arrangements of the two polymorphs are quite different, with form (Ia) having molecules that are stacked in an alternating arrangement, linked into chains of N—H...O hydrogen bonds along the crystallographic a direction, while form (Ib) has its N—H...O hydrogen‐bonded molecules stacked in a linear fashion. A theoretical study of the two structures allows information to be gained regarding other contributing interactions, such as π–π and weak C—H...F, in their crystal structures.     

Chiral crystals from an achiral molecule: 4,6‐di‐O‐benzyl‐1,3‐O‐benzylidene‐2‐O‐(4‐methoxybenzyl)‐myo‐5‐inosose

The title achiral compound, C₃₅H₃₄O₇, crystallizes in the chiral monoclinic space group P2₁. The molecules are densely packed to form a helical assembly along the crystallographic twofold screw axis via C—H...O and C—H...π interactions. Interestingly, the unit‐translated helical chains are loosely connected via a rather uncommon edge‐to‐edge Ph—H...H—Ph short contact (H...H = 2.33 Å).     

(2RS,5SR,6SR)‐Methyl 4‐{cis‐2‐[3‐fluoro‐5‐(4‐methoxy‐3,4,5,6‐tetrahydro‐2H‐pyran‐4‐yl)phenoxy­methyl]‐6‐hydroxy‐3‐phenylmorpholino}­benzene­sulfinate

The title compound, C₃₀H₃₄FNO₇S, is a key inter­mediate in the design of dual 5‐LOX (5‐lipoxygenase)/COX‐2 (cyclo­oxygenase‐2) inhibitors. The compound crystallizes as a racemate. Linear hydrogen‐bonded chains are aligned along the [201] direction, and stacked π–π inter­actions and C—H⋯O contacts stabilize the crystal structure.     

2‐Ethyl‐6‐methylpyridin‐3‐ol and its salt bis(2‐ethyl‐3‐hydroxy‐6‐methylpyridinium) succinate

The title compounds, C₈H₁₁NO, (I), and 2C₈H₁₂NO⁺·C₄H₄O₄²⁻, (II), both crystallize in the monoclinic space group P2₁/c. In the crystal structure of (I), intermolecular O—H...N hydrogen bonds combine the molecules into polymeric chains extending along the c axis. The chains are linked by C—H...π interactions between the methylene H atoms and the pyridine rings into polymeric layers parallel to the ac plane. In the crystal structure of (II), the succinate anion lies on an inversion centre. Its carboxylate groups interact with the 2‐ethyl‐3‐hydroxy‐6‐methylpyridinium cations via intermolecular N—H...O hydrogen bonds with the pyridine ring H atoms and O—H...O hydrogen bonds with the hydroxy H atoms to form polymeric chains, which extend along the [01] direction and comprise R₄⁴(18) hydrogen‐bonded ring motifs. These chains are linked to form a three‐dimensional network through nonclassical C—H...O hydrogen bonds between the pyridine ring H atoms and the hydroxy‐group O atoms of neighbouring cations. π–π interactions between the pyridine rings and C—H...π interactions between the methylene H atoms of the succinate anion and the pyridine rings are also present in this network.     

Structures of 1‐hydrophenanthroimidazoles: building blocks in the synthesis of expanded‐ring bis(imidazoles)

The structures of 1H‐phenanthro[9,10‐d]imidazole, C₁₅H₁₀N₂, (I), and 3,6‐dibromo‐1H‐phenanthro[9,10‐d]imidazole hemihydrate, C₁₅H₈Br₂N₂·0.5H₂O, (II), contain hydrogen‐bonded polymeric chains linked by columns of π–π stacked essentially planar phenanthroimidazole monomers. In the structure of (I), the asymmetric unit consists of two independent molecules, denoted (Ia) and (Ib), of 1H‐phenanthro[9,10‐d]imidazole. Alternating molecules of (Ia) and (Ib), canted by 79.07 (3)°, form hydrogen‐bonded zigzag polymer chains along the a‐cell direction. The chains are linked by π–π stacking of molecules of (Ia) and (Ib) along the b‐cell direction. In the structure of (II), the asymmetric unit consists of two independent molecules of 3,6‐dibromo‐1H‐phenanthro[9,10‐d]imidazole, denoted (IIa) and (IIb), along with a molecule of water. Alternating molecules of (IIa), (IIb) and water form hydrogen‐bonded polymer chains along the [110] direction. The donor–acceptor distances in these N(imine)...H—O(water)...H—N(amine) hydrogen bonds are the shortest thus far reported for imidazole amine and imine hydrogen‐bond interactions with water. Centrosymmetrically related molecules of (IIa) and (IIb) alternate in columns along the a‐cell direction and are canted by 48.27 (3)°. The present study provides the first examples of structurally characterized 1H‐phenanthroimidazoles.     

Amide hydrogen bonding: control of the molecular and extended structures of two symmetrical pyridine‐2‐carboxamide derivatives

The crystal structures of two symmetrical pyridine‐2‐carboxamides, namely N,N′‐(propane‐1,3‐diyl)bis(pyridine‐2‐carboxamide), C₁₅H₁₆N₄O₂, (I), and N,N′‐(butane‐1,4‐diyl)bis(pyridine‐2‐carboxamide), C₁₆H₁₈N₄O₂, (II), exhibit extended hydrogen‐bonded sequences involving their amide groups. In (I), conventional bifurcated amide–carbonyl (N—H)...O hydrogen bonding favours the formation of one‐dimensional chains, the axes of which run parallel to [001]. Unconventional bifurcated pyridine–carbonyl C—H...O hydrogen bonding links adjacent one‐dimensional chains to form a `porous' three‐dimensional lattice with interconnected, yet unfilled, voids of 60.6 (2) ų which combine into channels that run parallel to, and include, [001]. 4% of the unit‐cell volume of (I) is vacant. Compound (II) adopts a Z‐shaped conformation with inversion symmetry, and exhibits an extended structure comprising one‐dimensional hydrogen‐bonded chains along [100] in which individual molecules are linked by complementary pairs of amide N—H...O hydrogen bonds. These hydrogen‐bonded chains interlock viaπ–π interactions between pyridine rings of neighbouring molecules to form sheets parallel with (010); each sheet is one Z‐shaped molecule thick and separated from the next sheet by the b‐axis dimension [7.2734 (4) Å].     

Bis­(melaminium) dl‐malate tetrahydrate

The crystal structure of the title melaminium salt, bis(2,4,6‐tri­amino‐1,3,5‐triazin‐1‐ium) dl ‐malate tetrahydrate, 2C₃H₇N₆⁺·C₄H₄O₅²⁻·4H₂O, consists of singly protonated melaminium residues, dl ‐malate dianions and water mol­ecules. The melaminium residues are connected into chains by four N—H⃛N hydrogen bonds, and these chains form a stacking structure along the c axis. The dl ‐malate dianions form hydrogen‐bonded chains and, together with hydrogen‐bonded water mol­ecules, form a layer parallel to the (100) plane. The conformation of the malate ion is compared with an ab initio molecular‐orbital calculation. The oppositely charged moieties, i.e. the stacks of melaminium chains and hydrogen‐bonded dl ‐malate anions and water mol­ecules, form a three‐dimensional polymeric structure, in which N—H⃛O hydrogen bonds stabilize the stacking.     

N‐(2,6‐Dibromophenyl)formamide

In the crystal structure of the title compound, C₇H₅Br₂NO, molecules related by translation are linked through N—H...O hydrogen bonds to form chains in the crystallographic a direction, with the aryl rings stacked parallel to each other along the chain. Besides the N—H...O hydrogen bonds, Br...O and Br...Br intermolecular interactions complete the packing of molecules in the crystal structure.     

Br...O contacts and π–π stacking dominate the packing in methyl 4‐bromo‐3,5‐dimethoxybenzoate

The title compound, C₁₀H₁₁BrO₄, a useful precursor to pharmaceutically active isocoumarin and isochroman derivatives, crystallizes with two unique molecules in the asymmetric unit. A π–π stacking interaction links the planar molecules in the asymmetric unit. Additional π–π contacts stack pairs of molecules along the c axis. A feature of the crystal packing is the presence of a number of short Br...O contacts. A particularly unusual arrangement involves the formation of dimers, with pairs of Br...O contacts imposing a close Br...Br interaction and generating five‐membered rings within an eight‐membered ring formed by two Br...O contacts. Only two comparable arrangements have been reported previously. The Br...O contacts combine with weak C—H...O hydrogen bonds to form corrugated sheets of molecules approximately parallel to (001). These sheets are stacked along the c axis by π–π interactions to generate a three‐dimensional network.     

(S)‐3‐(Ammoniomethyl)‐5‐methylhexanoate (pregabalin)

The title compound, C₈H₁₇NO₂, exists as a zwitterion, adopting a propeller conformation. Molecules self‐assemble to form a hydrogen‐bonded layer parallel to the ab crystallographic plane connected by N⁺—H...O⁻ and C—H...O⁻ hydrogen bonds. These layers are stacked along the c axis and are stabilized by van der Waals interactions.     

Oxonium 5‐amino­uracil‐6‐sulfonate hydrate

In the title compound, oxonium 5‐amino‐2,6‐dioxo‐1,2,3,6‐tetra­hydro­pyrimidine‐4‐sulfonate hydrate, H₃O⁺·­C₄H₄­N₃­O₅S^?·­H₂O, the sulfonate group is in the anionic form and charge balance is provided by an o­xonium cation, H₃O⁺. Screw‐related mol­ecules overlap significantly and are hydrogen bonded to form a zigzag chain of the uracil skeleton along the direction of the c screw axis. The partially stacked bases and their glide‐related equivalents run parallel to the a axis to form hydro­phobic zones separated by hydro­philic zones built up by a network of hydrogen bonds.     

Two new polymorphs of 2,6‐diaminopyrimidin‐4(3H)‐one monohydrate

The title compound, C₄H₆N₄O·H₂O, crystallized simultaneously as a triclinic and a monoclinic polymorph from an aqueous solution of 2,4‐diaminopyrimidin‐6‐ol. Previously, an orthorhombic polymorph was isolated under the same experimental conditions. The molecular geometric parameters in the two present polymorphs and the previously reported orthorhombic polymorph are similar, but the structures differ in the details of their crystal packing. In the triclinic system, the diaminopyrimidinone molecules are connected to one another via N—H...O and N—H...N hydrogen bonding to form infinite chains in the [011] direction. The chains are further hydrogen bonded to the water molecules, resulting in a three‐dimensional network. In the monoclinic system, the diaminopyrimidinone molecules are hydrogen bonded together into two‐dimensional networks parallel to the bc plane. The water molecules link the planes to form a three‐dimensional polymeric structure.     

Synthesis and crystal structures of C24‐epimeric 20(R)‐ocotillol‐type saponins

Ocotillol‐type saponins have a wide spectrum of biological activities. Previous studies indicated that the configuration at the C24 position may be responsible for their stereoselectivity in pharmacological action and pharmacokinetics. Natural ocotillol‐type saponins share a 20(S)‐form but it has been found that the 20(R)‐stereoisomers have different pharmacological effects. The semisynthesis of 20(R)‐ocotillol‐type saponins has not been reported and it is therefore worthwhile clarifying their crystal structures. Two C24 epimeric 20(R)‐ocotillol‐type saponins, namely (20R,24S)‐20,24‐epoxydammarane‐3β,12β,25‐triol, C₃₀H₅₂O₄, (III), and (20R,24R)‐20,24‐epoxydammarane‐3β,12β,25‐triol monohydrate, C₃₀H₅₂O₄·H₂O, (IV), were synthesized, and their structures were elucidated by spectral studies and finally confirmed by single‐crystal X‐ray diffraction. The (Me)C—O—C—C(OH) torsion angle of (III) is 146.41 (14)°, whereas the corresponding torsion angle of (IV) is −146.4 (7)°, indicating a different conformation at the C24 position. The crystal stacking in (III) generates an R₄⁴(8) motif, through which the molecules are linked into a one‐dimensional double chain. The chains are linked via nonclassical C—H…O hydrogen bonds into a two‐dimensional network, and further stacked into a three‐dimensional structure. In contrast to (III), epimer (IV) crystallizes as a hydrate, in which the water molecules act as hydrogen‐bond donors linking one‐dimensional chains into a two‐dimensional network through intermolecular O—H…O hydrogen bonds. The hydrogen‐bonded chains extend helically along the crystallographic a axis and generate a C₄⁴(8) motif.