Enantiodifferent proton exchange in alanine and asparagine in the presence of H(2)(17)O.

Using Time Domain (1)H Nuclear Magnetic Resonance with H (2) (17) O (H (2) (17) O-TD-(1)HNMR), we found [H (2) (17) O]- and pH-controlled chiral differences in proton exchange properties in alanine (Ala) and asparagine (Asn). To minimize and equalize chemical impurities, Asn enantiomers were purified by crystallization from racemic solution. At <0.1 M H (2) (17) O, a shift in isoelectric pH (pI) occurred, approximately 1.14 kJ mol(-1) L: -D: -Asn DeltaDeltaG (o)' in the 5.91-6.42 pH range. One potential source for this asymmetry is the enantio-different magnetic moments (L: mu upward arrow not equal D: mu downward arrow) produced by neutral ring currents in the chiral center, leading to enantio-different nuclear spin organization and charge distribution in the amino group. At >or=pI, dissimilar interactions may occur in the hydration of the amino group with H (2) (17) O (NH(2)/H (2) (17) O not equal NH(2)/H (2) (16) O; NH(3) (+)/H (2) (17) O not equal NH(2)/H (2) (17) O; L: -*C-NH(2)/H (2) (17) O not equal D: -*C-NH(2)/H (2) (17) O). As L: mu upward arrow not equal D: mu downward arrow, the L: -*C-amino and the D: -*C-amino groups are diastereo spin-isomers. The nuclear spin of (17)O may be parallel or antiparallel with the ortho-(1)H(1)H pair; hence two ortho-H (2) (17) O molecules exist, also diastereo spin-isomers. As the pK of H (2) (17) O is different from H (2) (16) O, dissimilarities between L: -*C- and D: -*C-amino groups are converted into proton exchange differences. During H (2) (17) O-TD-(1)HNMR, the H (2) (17) O molecule is a "probe" of the state of the amino group. Regarding prebiotic evolution: prebiotic chirality may not require stochastic symmetry breaking or preexisting chiral conditions; chemical chiral effects due to L: mu upward arrow not equal D: mu downward arrow are small and need chiral amplification to generate an enantiomeric excess significant for prebiotic evolution; and prebiotic symmetry breaking was homochiral because the effect of L: mu upward arrow and D: mu downward arrow on the amino group should be similar in all alpha amino acids.

TD-1HNMR measurements show enantioselective dissociation of ribose and glucose in the presence of H2(17)O.

We used Time Domain (1)H Nuclear Magnetic Resonance (NMR) to characterize changes in proton exchange between water and sugar enantiomers at different concentrations of H(2)(17)O (approximately 15-450 mM) and found that dissociation of the (-)-enantiomers of glucose and ribose occurs at significantly higher rates at higher concentrations of H(2)(17)O. The mechanism behind this enantioselective effect is unclear. The hypothesis we propose is that the large magnetic field (B(o) approximately 0.6T) applied during NMR measurements induces electric moments opposite in sign for the D and L-isomers. Because (17)O has a nuclear electric quadrupole moment not = 0, asymmetrically hydrated complexes may form between the B(o)-polarized enantiomers and H(2)(17)O. Either H(2)(17)O is more often hydrating the (+) than the (-)-enantiomers--and consequently pK differences between H(2)(16)O and H(2)(17)O lead to differences in proton exchange between enantiomers and water--or the orientation of H(2)(17)O relative to the B(o)-polarized enantiomers is different, in total or in part, which leads to hydrated complexes with different spatial geometries and different proton exchange properties. This effect is significant for Magneto-Chiral Stereo-Chemistry (MCSC) and astrobiology, and it may help us better understand specific instances of mass independent isotopic fractionation and aid in the development of new technologies for chiral and isotopic separation.

Calcium Fructoborate for Bone and Cardiovascular Health.

Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex "protective" effect against inflammatory response. CF is commercially available in the USA as a "nature-identical" complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).

Effects of Calcium Fructoborate on Levels of C-Reactive Protein, Total Cholesterol, Low-Density Lipoprotein, Triglycerides, IL-1ß, IL-6, and MCP-1: a Double-blind, Placebo-controlled Clinical Study.

Calcium fructoborate (CFB) has been reported as supporting healthy inflammatory response. In this study, we assess the effects of CFB on blood parameters and proinflammatory cytokines in healthy subjects. This was a randomized, double-blinded, placebo-controlled trial. Participants received placebo or CFB at a dose of 112 mg/day (CFB-1) or 56 mg/day (CFB-2) for 30 days. Glucose, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), homocysteine, interleukin 1 beta (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1) were determined before and after supplementation. CFB-1 showed a reduction in blood levels of CRP by 31.3 % compared to baseline. CFB-1 and CFB-2 reduced LDL levels by 9.8 and 9.4 %, respectively. CFB-1 decreased blood homocysteine by 5.5 % compared with baseline, whereas CFB-2 did not have a significant effect. Blood levels of TG were reduced by 9.1 and 8.8 % for CFB-1 and CFB-2, respectively. Use of both CFB-1 and CFB-2 resulted in significantly reduced IL-6 levels, when compared within and between groups. IL-1ß was reduced by 29.2 % in the CFB-1 group. Finally, CFB-1 and CFB-2 reduced MCP-1 by 31 and 26 %, respectively. Our data indicate that 30-day supplementation with 112 mg/day CFB (CFB-1) resulted in a significant reduction of LDL, TG, TC, IL-1ß, IL-6, MCP-1, and CRP. HDL levels were increased, when compared to baseline and placebo. These results suggest that CFB might provide beneficial support to healthy cardiovascular systems by positively affecting these blood markers (ClinicalTrials.gov, ISRCTN90543844; May 24, 2012 ( http://www.controlled-trials.com/ISRCTN90543844 )).

Sugar-borate esters--potential chemical agents in prostate cancer chemoprevention.

The potential value of sugar-borate esters (SBEs) in the chemo-preventive therapy of prostate cancer has been reviewed. We propose that SBEs act as boron (B) vehicles, increasing the concentration of borate inside cancer cells relative to normal cells. Increased intracellular concentration of borate activates borate transporters, but also leads to growth inhibition and apoptosis. The effects of SBEs on normal cells are less dramatic because SBEs are naturally-occurring biochemicals, common and abundant in some fruits and vegetables, and also because borate dissociated from SBEs in natural diet doses is easily exported from normal cells. Cancer cell lines that over-express sugar transporters or under-express borate export are potential targets for SBE-based therapy. With regard to efficiency against cancer cells and drug preparation requirements, trigonal cis-diol boric monoesters will be one of the most effective class of SBEs. Because negative correlation exists between borate intake and the incidence of prostate cancer, and because most cancer cells overexpress sugar transporters, SBEs are proposed as a potential chemopreventive avenue in the fight against primary and recurrent prostate cancer.

Calcium fructoborate helps control inflammation associated with diminished bone health.

Inflammation has been identified as a possible contributory factor to disruption of the normal bone remodeling process, a process essential to healthy bone mineral density. Several large population-based clinical studies have specifically shown that levels of C-reactive protein, an immune recognition protein that is a sensitive marker of inflammation, are inversely and independently associated with total bone mineral density. The evidence suggests that control of C-reactive protein levels may contribute to bone health by protecting against inflammation's disruption of the equilibrium between bone resorption and bone deposition. Calcium fructoborate, a patented complex of calcium, fructose, and boron found naturally in fresh and dried fruits, vegetables and herbs, and wine, is a sugar-borate ester. A growing body of peer-reviewed, published clinical research indicates that the calcium fructoborate significantly reduces serum levels of the C-reactive protein in humans, suggesting that this unique plant-mineral complex may contribute to bone health by controlling the inflammation associated with loss of bone mineral density.

Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life.

OBJECTIVE: This study aimed to evaluate the effects of short-term (60-d) oral supplementation with calcium fructoborate, resveratrol, and their combination on the clinical and biological statuses of subjects with stable angina pectoris. METHODS: A randomized, double-blinded, active-controlled, parallel clinical trial was conducted in three groups of subjects. Of the total number of subjects included in study (n = 166), 87 completed the 60-d test treatment study period and 29 followed in parallel their usual medical care and treatment. The primary outcomes were inflammation biomarkers (high-sensitivity C-reactive protein), left ventricular function markers (N-terminal prohormone of brain natriuretic peptide), and lipid markers (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacylglycerols). Quality of life was assessed by the Canadian Cardiovascular Society angina class and the number of angina attacks per week. RESULTS: There was a significant decrease of high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits. This decrease was greater (39.7% at 60 d) for group 3 (calcium fructoborate), followed by group 2 (resveratrol plus calcium fructoborate, 30.3% at 60 d). The N-terminal prohormone of brain natriuretic peptide was significantly lowered by resveratrol (group 1, 59.7% at 60 d) and by calcium fructoborate (group 3, 52.6% at 60 d). However, their combination (group 2) was the most effective and induced a decrease of 65.5%. Lipid markers showed slight changes from baseline in all groups. The improvement in the quality of life was best observed for subjects who received the resveratrol and calcium fructoborate mixture (group 2). CONCLUSION: The results indicate that the combination of resveratrol and calcium fructoborate has beneficial effects in patients with angina

Calcium fructoborate--potential anti-inflammatory agent.

Calcium fructoborate is a boron-based nutritional supplement. Its chemical structure is similar to one of the natural forms of boron such as bis-manitol, bis-sorbitol, bis-fructose, and bis-sucrose borate complexes found in edible plants. In vitro studies revealed that calcium fructoborate is a superoxide ion scavenger and anti-inflammatory agent. It may influence macrophage production of inflammatory mediators, can be beneficial for the suppression of cytokine production, and inhibits progression of endotoxin-associated diseases, as well as the boric acid and other boron sources. The mechanisms by which calcium fructoborate exerts its beneficial anti-inflammatory effects are not entirely clear, but some of its molecular biological in vitro activities are understood: inhibition of the superoxide within the cell; inhibition of the interleukin-1ß, interleukin-6, and nitric oxide release in the culture media; and increase of the tumor necrosis factor-α production. Also, calcium fructoborate has no effects on lipopolysaccharide-induced cyclooxygenase-2 protein express. The studies on animals and humans with a dose range of 1-7 mg calcium fructoborate (0.025-0.175 mg elemental boron)/kg body weight/day exhibited a good anti-inflammatory activity, and it also seemed to have negligible adverse effect on humans.

In vitro effects of calcium fructoborate upon production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages.

The present study is supported by our previous findings suggesting that calcium fructoborate (CF) has anti-inflammatory and antioxidant properties. Thus, we investigated the effects of CF on a model for studying inflammatory disorders in vitro represented by lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. This investigation was performed by analyzing the levels of some mediators released during the inflammatory process: cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukins IL-1beta and IL-6 as well as cyclooxygenase-2 (COX-2), the main enzyme responsible for endotoxin/LPS-induced prostaglandin synthesis by macrophages. We also measured production of nitric oxide (NO) that plays an important role in the cytotoxicity activity of macrophages towards microbial pathogens. After CF treatment of LPS-stimulated macrophages we found an up-regulation of TNF-alpha protein level in culture medium, no significant changes in the level of COX-2 protein expression and a decrease in NO production as well as in IL-1beta and IL-6 release. Collectively, this series of experiments indicate that CF affect macrophage production of inflammatory mediators. However, further research is required in order to establish whether CF treatment can be beneficial in suppression of pro-inflammatory cytokine production and against progression of endotoxin-related diseases.

Rooting prebiotic chirality in spinomeric chemistry?

Spinomeric chemistry is a domain of physical chemistry that explores the role of spin-isomery in chemical reactivity. In large magnetic fields (B), chemical structures with three adjacent nuclear spins (such as H(2)(17)O, H(2)(33)S,-NH(2), and and -(13)CH(2)-) form complex spinomers. Known departure from a 1:1 ratio between various types of spinomers opens interesting research avenues in their potential role in asymmetric hydration processes. Recent time domain (1)H nuclear magnetic resonance (TD-(1)HNMR) findings revealed the existence of small, yet consistent, H(2)(17)O-controlled enantio-different proton exchange reactivity in sugars. The mechanisms behind this effect are unclear and may involve spinomer/enantiocenter (e.g., H(2)(17)O/*C) interactions or spinomer/spinomer (e.g., H(2)(17)O/-NH(2)) interactions. We developed an experimental model that allows for the verification and study of such effects. We used TD-(1)HNMR at 0.589 T to study and compare proton exchange enantio-differences in asparagine (Asn) and mandelic acid in response to titration with H(2)(17)O at constant pH. Unlike Asn, mandelic acid has no complex spinomer group (such as -NH(2)) in its chiral center. We report finding enantio-differences regarding DeltapK and 1/T(2)(0) correlated with H(2)(17)O, and linear changes in DeltaM(2) indicating differences in the affinity of enantiomers for H(2)(17)O surface hydration. These results stress the importance of H(2)(17)O-based spinomeric chemistry in chiral reactivity and open windows toward a novel interpretation of the origin of prebiotic chiral reactivity in the presence of moderately large B (such as on magnetic mineral surfaces or on satellites of gaseous giants), as well as toward abiotic isotopic fractionation of H(2)(17)O in the presence of chiral organic molecules.

Calcium fructoborate: plant-based dietary boron for human nutrition.

The main objective of this paper is to evaluate the scientific evidence on the form of organic boron, calcium fructoborate (CF), including health dates, dietary needs, pharmacology, experts opinion, research papers, clinical evidence, and dosing. CF is a natural product with effects in oxidative metabolism and cell apoptosis. We review the biological and biochemical action of chemical natural-identical entity of CF. This mini review provides support for future clinical research.