Pore size dependent dynamics of confined water probed by FIR spectroscopy.

We measured the FIR (Far Infrared) absorbance of a series of organic hydrated sub-nanopores (i.e. pores of the size of several A) containing confined water. Our results show that the FIR frequency region between 400 and 570 cm(-1) is sensitive to the differences in water mobility. The absorbance of these compounds was significantly higher than that of chemically similar anhydrous or non-porous hydrated compounds in the same region. Moreover, changes in the water dynamics inside the hydrated pores were found and characterized by their temperature dependent studies in the range from -5 to 20 degrees C. Upon increasing the temperature, water confined in narrow pores shows a small increase in FIR absorbance, while less confined water molecules inside larger pores exhibit a higher increase in absorbance, resembling more what has been observed for bulk water.

Temperature-induced water release and uptake in organic porous networks.

The behavior of water confined near nonpolar surfaces has important implications for a number of biological phenomena. In this type of confined environment the properties of "hydrophobicity" and "hydrophilicity" are closely related to the structure of the interfacial water, which in turn can depend on temperature in a very subtle way. Although the physical-chemical consequences of this fact have been theoretically addressed to a great extent, the underlying thermodynamic question is still widely discussed. Accordingly we performed thermogravimetric analysis and variable-temperature powder X-ray diffraction studies on representative hydrogen bonding organic pores occupied by water. The results indicate that a hydrophilic-to-hydrophobic transition of the inner surface of the pores occurs upon increasing temperature, which may be attributed to a strong influence of the dynamics and thermodynamics of local water molecules on the surface affinity of the pores. The relevance of our findings to the understanding of the phenomenon of water transport in natural pores is discussed.

Distinct dynamic behaviors of water molecules in hydrated pores.

Water molecules confined inside narrow pores are of great importance in understanding the structure, stability, and function of water channels. Here we report that besides the H-bonding water that structures the pore, the permanent presence of a significant, fast-moving fraction of incompletely H-bonded water molecules inside the pore should control the free entry and exit of water. This is achieved by means of complementary DSC and solid-state NMR studies. We also present compelling evidence from X-ray diffraction data that the cluster formed by six water molecules in the most stable cage-like structure is sufficiently hydrophobic to be stably adsorbed in a nonpolar environment.

Molecular diversity of voltage-gated sodium channel alpha and beta subunit mRNAs in human tissues.

Voltage-gated Na+ channels are composed of one alpha subunit and one or more auxiliary beta subunits. A reverse transcription-polymerase chain reaction assay was used to analyse the expression of the nine known alpha subunits (Na(v)1.1-Na(v)1.9) in 20 different human tissues. The mRNA expression of the currently known beta subunits (beta1, beta2, beta3 and beta4) was also assessed. The mRNAs of voltage-gated Na+ channel alpha and beta subunits were found in a wide variety of human tissues assayed and were present in neuronal and non-neuronal types of cells. These data suggest that, in addition to its well-established role in skeletal muscle, cardiac cells and neurons, voltage-gated Na+ channels might play important, still undetermined local roles in the regulation of cellular functions. These channels could emerge in the next future as potential, new therapeutic targets in the treatment of visceral diseases.

Synthesis and structure of hydroxyl acids of general structure 7,7-alkenyl/alkynyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid.

The open-ended hollow tubular structure formed by inclusion of water molecules in the packing of the hydroxyl acid 1 (R1 = CH2OH, R2 = ethyl groups) led to the synthesis and structural study of their unsaturated analogues. In this article we report on a general and practical large-scale synthesis of hydroxyl acids that possess alkenyl and alkynyl appendages. Substitution of the ethyl groups in 1 with unsaturated two-carbon appendages has a different effect on the molecular structure and on the hydrogen-bonding pattern. No variation has been induced by substitution of only one ethyl group with a vinyl one, although the substitution of both ethyl groups with vinyl or acetylene appendages has the greatest effect on the molecular structure and results in different hydrogen-bonding motifs.

Cause of hydration/dehydration in condensed organic materials: synthesis of hydrophobic pores.

[reaction: see text] The unique solid-state hydration/dehydration properties of the diacid (+/-)-1e in comparison with other homologues of the same family are studied. Hydrophobic enhancement, which is a consequence of the loss of water molecules from (+/-)-1e chains, is a property that can be exploited to achieve organic condensed systems for nonpolar molecules by interstitial van der Waals confinement.

Water molecules in hydroxy/acid networks as a competition between dynamics and bonding. Synthesis of a wet hydrophobic pore.

In a model formed by hydroxy acids with a general structure (+/-)-1, we found that solid-state structures depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together via carboxylic acid to alcohol hydrogen bonds. Homologue (+/-)-1n with conformationally flexible substituents, which allow conformational deformation gives, by way of the incorporation of water molecules, an efficient hexagonal assembly, which extends to the third-dimension to form tubular H-bonding networks. Each puckered channel can be described as being interconnected by closely packed hexagons in chair-like conformations. The ethyl groups presented in (+/-)-1n provided the volume required to lock the inner hexagonal wall into a rigid structure.

Tachykinins and tachykinin receptors in human uterus.

(1) Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women. (2) The neurokinin B (NKB) precursor PPT-B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT-A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT-C, the gene encoding the novel tachykinin peptide hemokinin-1 (HK-1), was present in trace amounts in the uteri from both pregnant and nonpregnant women. (3) Tachykinin NK(2) receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK(1) receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK(3) receptor was present only in tissues from nonpregnant women. (4) The mRNA expression of the tachykinin-degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women. (5) Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA>>SP>/=NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors. (6) The tachykinin NK(2) receptor-selective agonist [Lys(5)MeLeu(9)Nle(10)]NKA(4-l0) was approximately equipotent with NKA, but the tachykinin NK(1) and NK(3) receptor-selective agonists [Sar(9)Met(O(2))(11)]SP and [MePhe(7)]NKB were ineffective in the myometrium from nonpregnant women. (7) The uterotonic effects of [Lys(5)MeLeu(9)Nle(10)]NKA(4-10) were antagonized by the tachykinin NK(2) receptor-selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys(5)MeLeu(9)Nle(10)]NKA(4-10). (8) These data are consistent with a role of tachykinins in the regulation of human uterine function, and reinforce the importance of NK(2) receptors in the regulation of myometrial contraction.

Controlled incorporation of water molecules into carboxy hydrogen-bond networks: a designed approach.

The incorporation of water molecules into the hydrogen-bonded pattern of condensed organic materials implies an unfavorable entropic tradeoff resulting from water ordering. Here we show for a family of diacids of general structure (+/-)-1 that extended chains of anhydrous or hydrated structures can be prepared by controlling the steric factors that lead to the closest packing of individual components.

Ring-Closing Metathesis in the Synthesis of Large and Medium-Sized Oxacycles. Application to the Synthesis of Polyoxygenated Macrocycles.

Ring-closing olefin metathesis (RCM) catalyzed by Grubbs's ruthenium benzylidene complex 1 is applied to the synthesis of unsaturated rings ranging in size from seven to thirteen members in trans-fused polyether systems. Reaction occurs with great efficiency in the cyclization of oxepene and oxocene rings, but as ring size increases, yields drop. The influence of the final double bond position is also studied. Better yields and milder reaction conditions are observed when an additional oxygen atom is introduced on the diene. This feature has promoted the application of this reaction to the synthesis of polyoxygenated macrocycles (with sizes ranging from 15 to 21 members), with excellent results.

Simple Designs for the Construction of Complex Trans-Fused Polyether Toxin Frameworks. A Convergent Strategy Based on Hydroxy Ketone Cyclization of C-Linked Oxacycles.

A single, unified convergent strategy for the stereocontrolled synthesis of trans-fused polyethers was developed. It was demonstrated that the epimerization and reductive intramolecular coupling of hydroxy ketones in reactions with silane-Lewis acids (SI-LA) to generate ethers in C-linked oxacycles is affected by its conformational preference in a predictable manner. The obtained results make evident that the influence of hydrogen bonding between a hemiketal hydroxyl and a 1,3-diaxial C-O bond is regular and predictable and that convergent synthesis of trans-fused polyethers may confidently be conducted on driving ring closure to oxane rings under thermodynamic conditions